A Randomized Controlled Examiner-blind Phase ii Proof-of-principle Clinical Study Investigating the Efficacy of an Experimental Dentifrice Containing Sodium Bicarbonate, High Molecular Weight Sodium Hyaluronate and Sodium Fluoride on Gingivitis and Plaque Removal in a Population With Mild-moderate Plaque-induced Gingivitis
Phase: PHASE2
Conditions: Gingivitis
Sponsor: GlaxoSmithKline

GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 208175 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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CLINICAL PROTOCOL 
A RANDOMIZED CONTROLLED EXAMINER-BLIND PHASE II 
PROOF-OF-PRINCIPLE CLINICAL STUDY INVESTIGATING THE 
EFFICACY OF AN EXPERIMENTAL DENTIFRICE CONTAINING 
SODIUM BICARBONATE, HIGH MOLECULAR WEIGHT SODIUM 
HYALURONATE AND SODIUM FLUORIDE ON GINGIVITIS AND 
PLAQUE REMOVAL IN A POPULATION WITH MILD-MODERATE 
PLAQUE-INDUCED GINGIVITIS 
Protocol Number: 
208175 
Compound/Product Name: 
Experimental dentifrice containing 67% w/w 
sodium bicarbonate, 0.2% w/w high molecular 
weight sodium hyaluronate and 0.221% w/w 
sodium fluoride 
United States (US) Investigational New Drug 
(IND) Number: 
N/A 
European Clinical Trials Database (EudraCT) 
Number: 
N/A 
Other Regulatory Agency Identified Number: 
Health Canada Submission No. 250333 
Phase: 
IIa 
Sponsor Information 
Sponsor Name & Legal Registered 
Address 
GlaxoSmithKline Consumer Healthcare (UK) 
Trading Limited 
980 Great West Road, 
Brentford, 
Middlesex, TW8 9GS, 
United Kingdom (UK) 
Sponsor Contact Details 
GlaxoSmithKline Consumer Healthcare (GSK CH) 
Holdings (US) LLC 
184 Liberty Corner Rd,  
Warren, New Jersey (NJ) 07059,  
United States (US) 
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This document contains confidentiality statements that are not relevant for this publicly
available version

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 2 of 77 
Document History 
 
Document 
Version Summary of Changes  
Original protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
2.0 
• Addition of Health Canada CTA submission no. to 
the title page. 
• Addition of NPN no. for washout product and NPN 
no. for negative control product. 
• Update to inclusion criteria: a female subject of 
childbearing potential must have negative 
pregnancy test results at screening and baseline. 
• Corrected wording of reference to section 5.5.4 in 
the inclusion criteria. 
• Update to exclusion criteria to include: a subject 
with any other clinical serious or unstable 
conditions (e.g. cardiovascular diseases, diabetes, 
liver disorders and kidney disorders) which may 
affect study outcomes and/or subject safety. 
• Update to exclusion criteria to include: a subject 
with a bleeding disorder that may affect study 
outcomes and/or subject safety.  
• Addition of threshold of compliance with allocated 
study treatment. 
• Clarifying that statistical comparisons under 
secondary analyses are pairwise.  
Amendment 2 
3.0 
• Section 5.5.4 updated to clarify time period that 
intrauterine device or barrier method of 
contraception should be in place prior to study 
participation. Clarity of acceptability of male partner 
sterilization ≥3 months prior to study participation, 
or documentation of a 0 sperm count. 
• Section 13.3 updated to clarify that clinical study 
site personnel involved in providing subject care, or 
conduct of any of the dental assessments will not 
be responsible for obtaining written informed 
consent. 
Amendment 3 
4.0 
• Wash-out period amended to 10 to 28 days in the 
following sections: Study Design section of the 
Protocol Summary, Table 1-1, Sections 4.1, 4.2 
and 8.2.1. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 3 of 77 
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.   
 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 4  of 7 7  
Pri n ci p al I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e  
•  I c o nfir m a gree m e nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter n ati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P) g ui deli nes.  
•  I ac k n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y c o n d u ct. I a gree t o p ers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.  
•  I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he stu d y are i nf or m e d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei v es all a p pr o priate i nf or mati o n t hr o u g h o ut t h e st u d y. 
•  I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ul ati o ns of t he 
c o u ntr y i n w hic h t he re searc h is c o n d u cte d a n d t he Declarati o n of Helsi n ki. 
 
I n v esti gat or Na me: 
 
I n v esti gat or Q ualificati o ns: 
B D S  
I n v esti gat or Si g nat ure: 
 
Date of Si g nat ure/ A gree me nt:  
D D -M m m -Y Y Y Y  
 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
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Table of Contents 
Sponsor Information ............................................................................................................ 1 
Document History ............................................................................................................... 2 
Principal Investigator Protocol Agreement Page ................................................................ 4 
Table of Contents ................................................................................................................ 5 
1 
PROTOCOL SUMMARY ................................................................................................ 10 
1.1 
Schedule of Activities ............................................................................................ 14 
2 
INTRODUCTION ............................................................................................................. 16 
2.1 
Study Rationale ...................................................................................................... 17 
2.2 
Background ............................................................................................................ 18 
2.3 
Mechanism of Action/Indication ........................................................................... 18 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 19 
4 
STUDY DESIGN .............................................................................................................. 21 
4.1 
Overall Design ....................................................................................................... 21 
4.2 
Rationale for Study Design .................................................................................... 22 
4.3 
Justification for Dose ............................................................................................. 25 
4.4 
End of Study Definition ......................................................................................... 25 
5 
STUDY POPULATION .................................................................................................... 25 
5.1 
Type and Planned Number of Subjects ................................................................. 25 
5.2 
Inclusion Criteria ................................................................................................... 26 
5.3 
Exclusion Criteria .................................................................................................. 27 
5.4 
Randomization Criteria .......................................................................................... 29 
5.5 
Lifestyle Considerations ........................................................................................ 29 
5.5.1 
Dental Product/Treatment and Oral Hygiene Restrictions.................... 29 
5.5.2 
Dietary and Smoking Restrictions ........................................................ 29 
5.5.3 
Medication and Treatment Restrictions ................................................ 30 
5.5.4 
Contraception ........................................................................................ 30 
5.6 
Screen Failures ....................................................................................................... 31 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 31 
5.8 
Rater/Clinical Assessor Qualifications .................................................................. 32 
6 
INVESTIGATIONAL/STUDY PRODUCTS ................................................................... 32 
6.1 
Investigational/Study Product Supplies ................................................................. 32 
6.1.1 
Dosage Form and Packaging ................................................................. 34 
6.1.2 
Preparation and Dispensing ................................................................... 34 
6.2 
Administration ....................................................................................................... 34 
6.2.1 
Medication/Dosing Errors ..................................................................... 35 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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6.2.2 
Overdose ............................................................................................... 35 
6.3 
Investigational/Study Product Storage .................................................................. 36 
6.4 
Investigational/Study Product Accountability ....................................................... 36 
6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 37 
6.5 
Blinding and Allocation/Randomization ............................................................... 37 
6.6 
Breaking the Blind ................................................................................................. 37 
6.7 
Compliance ............................................................................................................ 38 
6.8 
Concomitant Medication/Treatments .................................................................... 38 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................... 38 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 38 
7.2 
Lost to Follow up ................................................................................................... 39 
8 
STUDY PROCEDURES ................................................................................................... 40 
8.1 
Screening: Visit 1 .................................................................................................. 40 
8.1.1 
Informed Consent .................................................................................. 40 
8.1.2 
Demographics ....................................................................................... 41 
8.1.3 
Medical History and Prior Medication/Treatment ................................ 41 
8.1.4 
Screening Procedures ............................................................................ 41 
8.1.6 
Gross Assessment of Gingival Health................................................... 42 
8.1.7 
Inclusion/Exclusion Criteria.................................................................. 42 
8.1.8 
Subject Eligibility.................................................................................. 42 
8.1.9 
Supervised Use of Washout Dentifrice ................................................. 42 
8.2 
Study Period........................................................................................................... 42 
8.2.1 
Baseline: Day 0 (Visit 2) ....................................................................... 42 
8.2.2 
Day 3, Day 7, Day 14 (Visits 3-5) ........................................................ 43 
8.2.3 
Day 42 (Visit 6) ..................................................................................... 44 
8.3 
Diary Review ......................................................................................................... 44 
8.4 
Dental Prophylaxis ................................................................................................. 45 
8.5 
End of Study Optional Prophylaxis ....................................................................... 45 
8.6 
Study Conclusion ................................................................................................... 45 
8.7 
Follow-up Visit/ Phone Call .................................................................................. 45 
9 
STUDY ASSESSMENTS ................................................................................................. 45 
9.1 
Screening Assessments .......................................................................................... 46 
9.1.1 
Gross Assessment of Gingival Health................................................... 46 
9.1.2 
Urine Pregnancy Testing ....................................................................... 46 
9.2 
Efficacy Assessments ............................................................................................ 46 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 7  of 7 7  
9. 2. 1  
M o difie d Gi n gi val I n d e x ( M GI) Ass ess me nt (
) ...... 4 7  
9. 2. 2  
Blee di n g I n d e x ( BI) Assess me nt (
 
) ..................................................................................................... 4 7  
9. 2. 3  
Pla q ue Discl os ure  .................................................................................. 4 8  
9. 2. 4  
Pla q ue I n de x ( T PI) Assess me nt (
) ........................... 4 8  
9. 2. 1  
Re peata bilit y Ass ess me nts  .................................................................... 4 9  
9. 3  
Safet y a n d Ot her Assess me nts  ............................................................................... 4 9  
9. 3. 1  
Oral S oft Tiss ue E x a mi nati o n ( O S T)  .................................................... 4 9  
9. 3. 2  
Oral Har d Tiss ue ( O H T) Assess me nt  ................................................... 5 0  
1 0  A D V E R S E E V E N T A N D S E RI O U S A D V E R S E E V E N T S  ........................................... 5 0  
1 0. 1  
Defi niti o n of a n A d verse E ve nt ( A E)  .................................................................... 5 0  
1 0. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E)  ....................................................... 5 1  
1 0. 3  
Re p orti n g of A d vers e E v e nts  ................................................................................. 5 2  
1 0. 3. 1  
Re p orti n g Peri o d  ................................................................................... 5 2  
1 0. 4  
Re p orti n g Pr oce d ures  ............................................................................................. 5 3  
1 0. 4. 1  
Re p orti n g of a n A d verse E ve nt  ............................................................. 5 3  
1 0. 4. 2  
Re p orti n g of a Seri o us A d verse E ve nt  .................................................. 5 4  
1 0. 5  
E val uati n g A d v erse E ve nts  .................................................................................... 5 5  
1 0. 5. 1  
Assess me nt of I nte nsit y ......................................................................... 5 5  
1 0. 5. 2  
Assess me nt of Ca usalit y  ....................................................................... 5 5  
1 0. 6  
F oll o w -u p of A d v erse E v e nts  ................................................................................ 5 6  
1 0. 7  
Wit h dra wal D ue t o a n A d verse E ve nt  ................................................................... 5 6  
1 0. 7. 1  
S p o ns or’s Re p orti n g Re q uire me nts t o Re g ulat or y A ut h orities a n d 
Et hics C o m mittees  ................................................................................ 5 6  
1 0. 8  
Pre g n a nc y  .............................................................................................................. 5 7  
1 0. 8. 1  
Ti me Peri o d f or  C ollecti n g Pre g n a nc y I nf or mati o n  .............................. 5 7  
1 0. 8. 2  
Acti o n t o be Ta ke n if Pre g na n c y Occ urs  .............................................. 5 7  
1 0. 9  
Defi niti o n of a n d Pr oce d ure f or Re p orti n g M e dical De vice I n ci de nts  .................. 5 8  
1 0. 9. 1  
Defi niti o n of a n I n ci d e nt ....................................................................... 5 8  
1 0. 9. 2  
Re p orti n g of I nci de nts a n d Malf u ncti o ns  .............................................. 5 8  
1 0. 9. 3  
F oll o w -u p of Me di cal De vice I nci de nts  ................................................ 5 9  
1 0. 9. 4  
Re g ulat or y a n d Et hics Re p orti n g Re q uir e me nts f or I nci de nts  .............. 6 0  
1 1  D A T A M A N A G E M E N T  .................................................................................................. 6 0  
1 1. 1  
Case Re p ort F or m  .................................................................................................. 6 0  
1 1. 2  
Data Ha n dli n g  ........................................................................................................ 6 1  
1 1. 2. 1  
Data Q ueries  .......................................................................................... 6 1  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI

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Protocol Number: 208175 
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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11.3 
Processing Patient Reported Outcomes ................................................................. 61 
11.4 
External Data ......................................................................................................... 62 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES. ................................. 62 
12.1 
Sample Size Determination ................................................................................... 62 
12.2 
Statistical Methods and Analytical Plan ................................................................ 62 
12.2.1 
Definition of Analysis Populations ....................................................... 63 
12.2.2 
Exclusion of Data from Analysis .......................................................... 63 
12.2.3 
Demographic and Baseline Characteristics ........................................... 63 
12.2.4 
Study Drug/Product Compliance and Use of Other Therapies ............. 63 
12.2.5 
Primary Analysis(es) ............................................................................. 64 
12.2.6 
Secondary Analysis(es) ......................................................................... 64 
12.2.7 
Safety Analyses ..................................................................................... 65 
12.2.8 
Exploratory Analyses ............................................................................ 65 
12.2.9 
Other Analyses ...................................................................................... 66 
12.2.10 
Handling of Dropouts and Missing Data .............................................. 67 
12.2.11 
Interim Analysis .................................................................................... 67 
13 STUDY GOVERNANCE CONSIDERATIONS .............................................................. 67 
13.1 
Quality Control ...................................................................................................... 67 
13.2 
Quality Assurance .................................................................................................. 68 
13.3 
Regulatory and Ethical Considerations ................................................................. 68 
13.3.1 
Institutional Review Board/ Ethics Committee ..................................... 68 
13.3.2 
Ethical Conduct of the Study ................................................................ 68 
13.3.3 
Subject Information and Consent .......................................................... 69 
13.3.4 
Subject Recruitment .............................................................................. 69 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 69 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ................. 70 
13.5 
Provision of Study Results to Investigators ........................................................... 70 
13.6 
Records Retention .................................................................................................. 70 
13.7 
Conditions for Terminating the Study ................................................................... 71 
14 REFERENCES .................................................................................................................. 71 
15 APPENDICIES .................................................................................................................. 75 
15.1 
Product Usage Instructions .................................................................................... 75 
15.2 
ABBREVIATIONS ............................................................................................... 76 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
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List of in text tables 
Table 1-1 
Schedule of Activities ........................................................................... 14 
Table 3-1 
Study Objectives and Endpoints ........................................................... 19 
Table 6-1 
Investigational/Study Product Supplies ................................................ 32 
Table 6-2 
Sundry Items ......................................................................................... 32 
Table 9-1 
Modified Gingival Index scoring system .............................................. 47 
Table 9-2 
Bleeding Index scoring system ............................................................. 48 
Table 9-3 
Turesky Plaque Index Scoring System ................................................. 49 
Table 15-1 
Abbreviations ........................................................................................ 76 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
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1 
PROTOCOL SUMMARY  
Background and Rationale 
GlaxoSmithKline Consumer Healthcare (GSKCH) has developed an experimental dentifrice 
containing 67% weight for weight (w/w) sodium bicarbonate, 0.2% w/w high molecular weight 
(HMW) sodium hyaluronate and 0.221% w/w sodium fluoride for the treatment of gingivitis 
and plaque accumulation. This follows published literature evidence of 0.2% w/w HMW 
sodium hyaluronate in a gel format demonstrating efficacy in the treatment of gingivitis when 
used as an adjunct to regular toothbrushing. Given that there are currently no published clinical 
data investigating the efficacy of sodium hyaluronate (hyaluronic acid, HA) in a toothpaste for 
the treatment of gingivitis, a Proof-of-Principle (PoP) clinical study is required to explore the 
inclusion of HMW sodium hyaluronate in a twice-daily use sodium bicarbonate/ sodium 
fluoride toothpaste. This PoP study will investigate the efficacy of an experimental dentifrice 
containing 0.2% w/w HMW sodium hyaluronate in a twice daily use 67% w/w sodium 
bicarbonate/ 0.221% w/w sodium fluoride toothpaste compared to a regular fluoride dentifrice, 
and also whether this provides any additional benefit in reducing gingival inflammation/ 
bleeding compared with a 67% w/w sodium bicarbonate/ 0.221% w/w sodium fluoride 
containing toothpaste. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), after 6 weeks’ twice daily 
toothbrushing. 
Number (no.) of bleeding sites at 6 weeks. 
Secondary 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), after 6 weeks’ twice daily 
toothbrushing. 
Number (no.) of bleeding sites at 6 weeks. 
To evaluate the efficacy of a dentifrice 
containing 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride compared to a 
fluoride control dentifrice, for the assessment of 
gingivitis, as measured by a Bleeding Index (BI), 
after 6 weeks’ twice daily toothbrushing. 
 
Number (no.) of bleeding sites at 6 weeks.  
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Exploratory 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), over 2 weeks’ twice daily 
use. 
No. of bleeding sites at 3 days, 1 and 2 weeks. 
 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), over 6 weeks’ twice daily 
use. 
Mean BI at 3 days, 1, 2 and 6 weeks. 
 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by 
Modified Gingival Index (MGI), over 6 weeks 
twice daily use. 
Mean MGI at 3 days, 1, 2 and 6 weeks. 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of plaque accumulation, as 
measured by a Plaque Index (TPI; overall and 
interproximal), over 6 weeks twice daily use. 
Mean TPI (overall and interproximal) at 3 days, 
1, 2 and 6 weeks. 
To evaluate and compare MGI and mean BI in 
low (<45 bleeding sites) and high (>45 bleeding 
sites) BI subgroups following twice daily use of 
an experimental dentifrice containing 67% w/w 
sodium bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride, a 
67% w/w sodium bicarbonate/ 0.221% w/w 
sodium fluoride dentifrice and a fluoride control 
dentifrice, over 6 weeks twice daily use. 
 
 
Mean MGI and mean BI at 3 days, 1, 2 and 6 
weeks within each subgroup (low and high 
number of bleeding sites) 
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Protocol Number: 208175 
 
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Safety 
To assess the oral tolerability of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride, a 
67% w/w sodium bicarbonate/ 0.221% w/w 
sodium fluoride dentifrice, and a fluoride control 
dentifrice over 6 weeks twice daily use. 
Treatment-emergent adverse events over 6 
weeks. 
Study Design 
This will be a single center, controlled, single blind (examiner blind), randomized, stratified 
(gender and baseline number of bleeding sites) three-treatment arm, parallel design, clinical 
study. Study subjects will be aged 18-65 years, non-smokers, in good general health with 
generalized mild-moderate plaque-induced gingivitis and ≥ 20 natural teeth that meet all study 
criteria at both the Screening and Baseline visits (including ≥ 40 evaluable surfaces for MGI, 
BI, and TPI). 
Approximately 120 (n=40/group) subjects will be randomized to one of the study products. 
This study will consist of 6 study visits. At Visit 1, Screening, after signing informed consent, 
subjects will undergo an Oral Soft Tissue (OST) examination, an Oral Hard Tissue (OHT) 
examination and a gross assessment of gingival health, in addition to the standard (inclusion, 
exclusion, medical history, demographics, prior/current medications) procedures to assess 
eligibility for the study. Subjects will return to site 10-28 days after the Screening Visit, for 
Visit 2, Baseline.  
At the Baseline Visit, subjects will undergo, in the following order, a full OST/ OHT 
examination followed by assessments of gingival inflammation (MGI), gingival bleeding (BI) 
and supra-gingival plaque using the Turesky Plaque Index (TPI). Eligible subjects will be 
stratified based on gender and baseline number of bleeding sites (Low: < 45/ High ≥ 45 bleeding 
sites), to ensure a balance of gingivitis across both treatment groups and then randomized to 
study product. 
Subjects with mean MGI or TPI 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 for all clinical assessments (MGI, TPI, BI). 
All randomized subjects will then receive a full mouth dental prophylaxis (followed by flossing) 
to remove sub and supra-gingival calculus, stain, plaque and debris from the teeth. All subjects 
will enter the treatment period with no visible plaque (TPI=0).  
After all clinical assessments, subjects will be instructed to brush for 1 timed minute, in their 
usual manner, with their assigned study product and then instructed to continue using their 
assigned product twice daily (morning and evening), after which they will return to site for their 
Day 3 (Visit 3) assessments. Subjects will then continue using their assigned dentifrice for 1 
and 2 weeks (Visits 4 and 5), after which they will return for their Week 6 (Visit 6) assessments. 
Subjects will continue to record all brushing events in the diary provided, and this will be 
reviewed by the site at each study visit. 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 1 3  of 7 7  
After t h e Wee k  6  visit, st u d y cl ose o ut pr oce d ures (ret ur n of st u d y pr o d uct etc.) will ta ke pl ace 
a n d t he s u bj ect ma y u n der g o  a n a d diti o nal pr o p h yl a xis if it is dee me d necess ar y b y t h e e x a mi ner.  
Safet y a n d oral t olera bilit y of t he st u d y pr o d ucts will be m o nit ore d o ver t he 6 -wee k treat me nt  
peri o d b y re vie w of re p orte d A d verse E ve nt s a n d Inci de nts.  
St u d y I n v e sti g ati o n al Pr o d u ct s  
Tr e at m e nt 
D e s cri pti o n  
E x p eri m e nt al 
Pr o d u ct  
P o siti v e c o ntr ol  
N e g ati v e c o ntr ol  
D e ntifri c e 
c o nt ai ni n g 6 7 % 
w/ w s o di u m 
bi c ar b o n at e, 0. 2 % 
w/ w s o di u m 
h y al ur o n at e a n d 
0. 2 2 1 % w/ w  
s o di u m fl u ori d e  
D e ntifri c e 
c o nt ai ni n g 6 7 % 
w/ w s o di u m 
bi c ar b o n at e a n d 
0. 2 2 1 % w/ w  
s o di u m fl u ori d e  
D e ntifri c e 
c o nt ai ni n g 
1 1 0 0 p p m fl u ori d e 
a s s o di u m fl u ori d e  
Pr o d u ct N a m e  
E x p eri m e nt al 
d e ntifri c e  
 
R e gi st er e d a s a 
N o n -pr e s cri pti o n 
N at ur al H e alt h 
Pr o d u ct (N N H P ) 
i n C a n a d a 
 
( N P N n o. 
) 
 Cr e st C a vit y 
Pr ot e cti o n  
( C a n a di a n 
m ar k et pl a c e)  
( N P N  
) 
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s  
S ufficie nt s u bjects ( meeti n g t he i ncl usi o n/ e x cl usi o n criteria) will be scree ne d (a p pr o xi matel y 
1 6 0  s u bjects) t o ra n d o mize 1 2 0 s u bjects ( 4 0 per treat me nt gr o u p) t o e ns ure 1 0 8  e val ua bl e 
s u bjects ( 3 6 e val ua ble s u bjects per gr o u p) c o m plete t he wee k 6 ass ess me nt (t h us all o wi n g f o r 
a 1 0 % dr o p-o ut r ate).  
St ati sti c al A n al y s e s  
T he pri mar y efficac y v aria ble  is t he n u m ber of blee di n g sites at 6 wee ks. N u m ber of blee di n g 
sites will be calc ulate d as t he n u m ber of sites wit h a blee di n g i n de x sc ore of 1 or 2.  
T he n u m ber of blee di n g sites at  6 wee ks will be a nal yze d usi n g a n  A nal ysis of C o varia nce  
(A N C O V A ) m o del wit h treat me nt gr o u p a n d ge n d er as fact ors a n d bas eli ne n u m ber of blee di n g 
sites as c o variat e.  
A dj uste d mea ns a n d  treat me nt differe nces bet wee n t he 6 7 % w/ w s o di u m bicar b o nate & 0. 2 % 
w/ w H M W s o di u m h yal ur o nate a n d t he fl u ori de c o ntr ol de ntifrice  will be pr o vi de d al o n g wit h 
9 5 % c o nfi de n ce i nter vals . 
 
 
 
 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 14 of 77 
1.1 
Schedule of Activities 
The schedule of activities table provides an overview of the subject visits and study procedures.   
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, to conduct evaluations or assessments required to protect the well-being 
of the subject. 
Table 1-1 
Schedule of Activities 
 
Procedure/Assessment 
Screening 
 
Study Period 
Visit 1 
(-28 to -10 
days) 
Washout Period: minimum 10 Days/ maximum 28 days 
Visit 2 
Day 01 
Baseline 
Visit 3 
Day 3+1 
days1 
Visit 4 
Day 7±2 
(Week 1)1 
Visit 5 
Day 14±2 
(Week 2)1 
Visit 6 
Day 42±3 
(Week 6)1 
Informed consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Prior/ current medications 
and treatments 
X 
X 
 
 
 
 
Oral soft tissue (OST) 
examination 
X 
X 
X 
X 
X 
X 
Oral hard tissue (OHT) 
examination 
X 
X 
 
 
 
X 
Gross gingival assessment2 
X 
 
 
 
 
 
Urine pregnancy test7 
X 
X 
 
 
 
 
Inclusion/ Exclusion Criteria 
X 
X 
 
 
 
 
Subject Eligibility 
X 
X 
 
 
 
 
Subject Continuance 
 
 
X 
X 
X 
X 
Dispense washout 
dentifrice, toothbrush, diary 
& timer 
X 
 
 
 
 
 
Oral hygiene instruction & 
supervised brushing with 
washout dentifrice 
X 
 
 
 
 
 
Return washout products/ 
compliance checks 
 
X 
 
 
 
 
Concomitant medications & 
treatments 
 
X 
X 
X 
X 
X 
Modified Gingival Index 
(MGI) assessment3 
 
X 
X 
X 
X 
X 
MGI repeat assessment3 
 
X 
X 
X 
X 
X 
Bleeding Index (BI) 
assessment 
 
X 
X 
X 
X 
X 
Plaque disclosure & Plaque 
Index (TPI) assessments 
 
X 
X 
X 
X 
X 
TPI repeat assessment3 
 
X 
X 
X 
X 
X 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 15 of 77 
Stratification/randomization 
 
X 
 
 
 
 
Sub- & supra-gingival 
prophylaxis with 2nd 
examiner to confirm TPI=0 
via plaque disclosure 
 
X 
 
 
 
 
Dispense study products4 
 
X 
 
 
 
 
Collect study products, 
assess compliance and 
return to subject 
 
 
X 
X 
X 
 
Oral hygiene instruction & 
supervised brushing with 
study product at site 
 
X 
X 
X 
X 
 
Return all study products to 
site 
 
 
 
 
 
X 
End of study dental 
prophylaxis (optional)5 
 
 
 
 
 
X 
Adverse Events/ Incidents8 
X 
X 
X 
X 
X 
X 
Study Conclusion 
 
 
 
 
 
X 
Abbreviations: OST = Oral Soft Tissue; OHT = Oral Hard Tissue; MGI = Modified Gingival Index; BI = 
Bleeding Index; TPI = Turesky Plaque Index 
Footnotes: 
1. Subjects will abstain from overnight toothbrushing for a minimum of 12hrs (+6hr, -2hr) immediately 
prior to the assessment visits (Visits 2, 3, 4, 5 and 6) 
2. In relation to the general dentition inclusion/ exclusion criteria 
3. At least 2 repeatability assessments should be performed each day (≥ 1 in the morning; ≥ 1 in the 
afternoon) 
4.  Study products include study dentifrice, toothbrush, study instructions, diary & timer. Subjects will be 
instructed to bring all supplies to site at subsequent visits to determine treatment compliance, prior to 
being returned to the subject.  
5.  Prophylaxis will be offered to subjects who are deemed to require it in the opinion of the investigator/ 
examiner after all efficacy measures have been completed. This will be documented in the CRF. 
7. Female subjects of child bearing potential only 
8. Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs), and Incidents will be 
collected immediately after a subject provides consent to participate in the study by the completion of 
the Informed Consent Form (ICF). 
 
 
 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 1 6  of 7 7  
2  
I N T R O D U C TI O N 
Gi n gi vitis is a  re versi ble i nfla m mat or y res p onse t o t he prese nce of de ntal pla q ue  (
 
), w hic h t y picall y pres e nts as re d n ess, s welli n g ( oe d e ma) a n d/ or blee di n g of t h e 
g u ms at t he gi n gi val mar gi n s urr o u n di n g t he t o ot h . Gi n gi vitis is a re versi ble c o n diti o n b ut, if 
left u ntreate d, ca n pr o gress t o t he irre versi ble p hase of p eri o d o ntitis, w here i nfl a m mati o n 
e xte n ds t o t he u n derl yi n g tiss ues, peri o d o ntal li ga me nt a n d al ve olar b o ne. T he res ulti n g l oss of 
t hese str uct ures ca n e v e nt uall y l ea d t o t o ot h l oss t hr o u g h destr u cti o n of t he peri o d o ntal tiss ues 
s u p p orti n g t he t o ot h (
). Peri o d o ntitis is re p orte d t o affect 5 -2 0 % of 
t he w orl d’s p o p ulati o n 
). T he mai nte na nce of g o o d gi n gi val healt h 
is t heref ore i m p orta nt i n pre ve nti n g gi n gi vitis a n d t he de v el o p me nt of peri o d o ntal diseas e 
(
).  
De ntal pla q u e is a s oft, stic k y, c ol o urless de p osit of bacteria w hic h c ollects o n teet h a n d al o n g 
t he gi n gi val mar gi n; it is t he ca usati ve a gent of gi n gi vitis a n d peri o d o ntitis (
 
. Gi n gi vitis de vel o ps w he n pla q ue elicits a l o cal 
i nfla m mat or y res p o nse i n t he gi n gi vae at t he sit e of its acc u m ulati o n (
 
. Gi n gi vitis is pre ve nte d a n d res ol ve d t hr o u g h effecti ve pla q ue c o ntr ol, pri maril y vi a 
mec ha nic al pla q ue re m o val (i.e. t o ot h br us hi n g) (
 
).  
Ma n y pe o ple are u na ble t o ac hie v e a d e q uate pl a q u e c o ntr ol b y t o ot h br us hi n g al o ne.  T he effect 
of t o ot h br us hi n g ca n be a u g me nte d b y t he use of a de ntifrice 
) a n d a nti micr o bial 
i n gre di e nts. 
A nti micr o bial a ge nts (s uc h as 
metal salts, cet yl p yri di ni u m c hl ori de a n d 
c hl or he xi di ne) ha ve bee n i ncl u de d i n dail y use de ntifrice a n d m o ut h ri nse f or m ulati o ns f or 
ma n y years, wit h a vie w t o deli veri n g i m pr o v e d pla q ue c o ntr ol a n d g u m healt h be nefits 
(
). T he y c o m ple me nt mec h a nical pla q ue re m o v al b y i n hi biti n g t he gr o wt h 
of bact eria ( via bacteri ost atic a n d/ or b acterici dal acti vit y ) i n areas of t he m o ut h less accessi ble 
t o t he t o ot h br us h a n d b y i nterferi n g wit h t he re-c ol o nisati o n of pla q ue bacteria (
 
).  
G S K C H  mar kets a s o di u m bicar b o nate d e ntifrice ( 6 7 % w/ w; par o d o nta x) f or t he tr eat me nt of 
gi n gi vitis. T his is s u p p orte d b y a lar ge b o d y of e vi de nce de m o nstrati n g its efficac y a gai nst 
gi n gi vitis. S pecificall y, t w o cli nical st u dies c o n d u cte d i n t he U S i n vesti gate d blee di n g ( bl ee di n g 
i n de x [ BI]), gi n gi v al i nfla m mati o n ( m o difie d gi n gi val i n de x [ M GI]) a n d pla q ue ( pla q u e i n de x 
[ T PI]) o utc o m e meas ures after 2 4 wee ks i n d urati o n, wit h t wice dail y us e (G S K C H Cli nical 
St u d y R H 0 2 4 3 3/ 2 0 2 1 9 2, 2 0 1 7 ; 
). 
T here are c urre ntl y n o p u blis he d cli nical data i n vesti gati n g t he a p plicati o n of H M W s o di u m 
h yal ur o n ate i n a t o ot h paste f or t he tr eat me nt of gi n gi vitis. A Pr o of -of -Pri nci ple ( P o P ) cli nical 
st u d y is t heref ore bei n g c o n d ucte d  t o e x pl ore t he i ncl usi o n of s o di u m h yal ur o nate i n a t wice-
dail y use t o ot h past e. T his will pr o vi de data t o hel p u n dersta n d w het her H M W s o di u m 
h yal ur o n ate i n a t wice d ail y use 6 7 % w/ w s o di u m bicar b o nate/ 0. 2 2 1 % w/ w s o di u m fl u ori de 
t o ot h paste pr o vi des a d diti o nal be nefit i n re d u ci n g gi n gi val i nfla m mati o n/ blee di n g c o m pare d 
wit h a  re g ular fl u ori de d e ntifrice, al o n g wit h c o m pari n g t o a t o ot h paste c o ntai ni n g 6 7 % w/ w  
s o di u m bicar b o nate/ 0. 2 2 1 % w/ w s o di u m fl u ori de. 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 1 7  of 7 7  
2. 1  
St u d y R ati o n al e  
T here are c urre ntl y n o p u blis he d cli nical data i n vesti gati n g t he effi cac y of H M W s o di u m 
h yal ur o n ate ( h yal ur o nic aci d, H A) i n a t o ot h paste f or t he treat me nt of gi n gi vitis. A P o P  cli nical 
st u d y is t heref ore re q uir e d t o e x pl ore t he i ncl usi o n of H M W s o di u m h yal ur o nate i n a t wice -
dail y use s o di u m bic ar b o nate t o ot h paste. T his will pr o vi de data t o h el p u n d ersta n d w het her 0. 2 % 
w/ w  H M W  s o di u m h yal ur o nate i n a t wice dail y us e 6 7 % w/ w s o di u m bicar b o nate/ 0. 2 2 1 % w/ w 
t o ot h paste pr o vi des a n y be nefit i n re d u ci n g gi n gi val i nfla m mati o n/ blee di n g c o m pare d wit h a 
re g ular flu ori d e de ntifric e, a n d w het her it pr o vi des a n y a d diti o nal be nefit c o m pare d t o a 6 7 % 
w/ w s o di u m bicar b o nate/ 0. 2 2 1 % w/ w c o ntai ni n g d e ntifrice . T he rati o nale f or i ncl usi o n of 0. 2 % 
w/ w H M W s o di u m h yal ur o nate relates t o e vi de nce of 0. 2 % w/ w H M W s o di u m h yal ur o nate gel 
de m o nstrati n g efficac y i n t he treat me nt o f gi n gi vitis w he n use d as a n a dj u nct t o re g ular 
t o ot h br us hi n g (
 
).  
T he ai m  of t his pr o of of pri nci ple cli nical st u d y is t o e val uate t he efficac y of a n e x peri me ntal 
de ntifrice c o ntai ni n g 6 7 % w/ w s o di u m bi car b o nate , 0. 2 % w/ w H M W s o di u m h yal ur o nate a n d 
0. 2 2 1 % w/ w s o di u m fl u ori de t o c o ntr ol gi n gi vitis ( gi n gi val blee di n g a n d vis ual si g ns of gi n gi v al 
i nfla m mati o n) i n healt h y a d ult v ol u nteers wit h ge neralize d mil d t o m o derate gi n gi vitis o ver 6 
wee ks’ us e t hr o u g h t wice dail y t o ot h br us hi n g.  
Se veral cli nical st u dies e val uate d  t he a nti-gi n gi vitis efficac y of a s o di u m bi car b o nat e de ntifrice 
i n t he scie ntific literat ure. T hese st u dies ra n ge fr o m 4 wee ks t o 6 m o nt hs use (
 
 
 
) al o n g wit h  a pla q ue re-gr o wt h m o del o ver 4 -d a ys (
). 
Ta ke n t o get her, G S K C H  s p o ns ore d, a n d e xter nall y p u blis he d st u dies de m o nstrate effi cac y of 
s o di u m bicar b o nate c o nt ai ni n g d e ntifrice a gai nst meas ures of gi n gi vitis, al o n g wit h a fa v ora ble 
safet y pr ofile. 
T here are c urre ntl y n o k n o w n cli nical  st u dies, c o n d ucte d eit her wit hi n G S KC H  or e xter nal 
p u blis he d st u dies, i n vesti gati n g t he effect of  H M W  s o di u m h yal ur o n ate wit hi n a de ntifrice i n 
relati o n t o oral h ealt h be n efits. Gi ve n t his lac k of d ata f or a de ntifrice f or mat, se veral p u blis he d 
st u dies o n ot her f or mats s uc h as gels or s pra ys, ha v e bee n i de ntifie d, a n d i ncl u di n g 2 s yste mati c 
re vie ws w hic h c o n cl u de t hat t he maj ori t y of cli nical st u dies descri be a p ositi ve be neficial, 
occasi o nall y statisticall y si g nifi ca nt, effect of H M W s o di u m h yal ur o nat e o n gi n gi val healt h 
(
). Se v eral cli nical st u dies i n vesti gate  the a nti -gi n gi vitis 
effic ac y of s o di u m h yal ur o nate (
 
 All re p ort e d re d u cti o ns i n gi n gi vitis (gi n gi v al blee di n g 
a n d/ or gi n gi val i nfl a m mati o n) f or t h e s o di u m h yal ur o n ate tr eat me nt, c o m pare d t o pl ace b o/ 
c o ntr ol treat me nts; s o m e als o re p orte d re d ucti o ns i n s u pra -gi n gi val pla q ue a n d gi n gi val 
cre vic ular fl ui d ( G C F ) v ol u me/ c o m p ositi o n.  
C o m plete i nf or m ati o n f or t he e x peri me ntal 6 7 % w/ w s o di u m bicar b o nate , 0. 2 % w/ w H M W 
s o di u m h yal ur o n ate a n d 0. 2 2 1 % w/ w s o di u m fl u ori de ma y b e f o u n d i n t he si n gl e refere nce 
safet y d oc u me nt ( S R S D), w hic h f or t his st u d y is t he I n vesti gat or’s Br oc h ure (I B). 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 18 of 77 
2.2 
Background 
parodontax is a specialist gum health toothpaste that contains high levels of sodium bicarbonate 
(62-67% w/w) to facilitate removal of plaque bacteria thereby reducing gingivitis and has a 
large body of evidence in support of anti-gingivitis and plaque removal efficacy. This PoP study 
investigates the inclusion of 0.2% w/w HMW sodium hyaluronate to the 67% sodium 
bicarbonate dentifrice formulation for use as a twice daily use dentifrice; the aim to develop a 
daily use toothpaste containing sodium hyaluronate with the intention of providing improved/ 
fast gum healing. 
Sodium hyaluronate is a naturally occurring polysaccharide (glycosaminoglycan) which plays 
a role in the function of extracellular matrices, including those of mineralized and non-
mineralised periodontal tissues. It is a critical component of the extracellular matrix and 
contributes significantly to tissue hydrodynamics, cell migration and reduced proliferation and, 
at low (rather than high) molecular weight, plays a potentially important anti-inflammatory role 
through the inhibition of tissue destruction and facilitated healing. The use of sodium 
hyaluronate is already established in orthopaedics, dermatology and ophthalmology. 
A limited number of studies have reported the efficacy of HMW sodium hyaluronate in the oral 
environment (in gel, mouthwash and spray forms) for the treatment of gingivitis, with most 
available evidence based on the gel format (0.2% w/w HMW sodium hyaluronate) when used 
as an adjunct to regular toothbrushing. To date, there are currently no clinical data supporting 
the application of sodium hyaluronate in a daily use toothpaste for the treatment of gingivitis.  
Since there are currently no published clinical data investigating the application of HMW 
sodium hyaluronate in a toothpaste for the treatment of gingivitis, a PoP clinical study is 
required to explore the inclusion of HMW sodium hyaluronate in a twice-daily use toothpaste. 
This will provide data to help understand whether HMW sodium hyaluronate in a twice daily 
use 67% w/w sodium bicarbonate/ 0.221% w/w sodium fluoride toothpaste provides any benefit 
in reducing gingival inflammation/ bleeding compared with a regular fluoride dentifrice along 
with whether there is any additional benefit compared to a 67% w/w sodium bicarbonate/ 0.221% 
w/w sodium fluoride dentifrice (i.e. without inclusion of sodium hyaluronate).  
The main aim of the current PoP study is to investigate the efficacy profile of an experimental 
dentifrice containing 67% w/w sodium bicarbonate, 0.2% w/w HMW sodium hyaluronate and 
0.221% w/w sodium fluoride compared to a regular fluoride negative control dentifrice, for 
gingival bleeding (primarily assessed by number of bleeding sites), inflammation, and plaque 
removal, at multiple time points over a 6-week treatment period. In addition, early timepoints 
will also be investigated (3 days, 1 & 2 weeks for inflammation), relating to published evidence 
of improved gingival health and plaque accumulation with adjunctive use of sodium 
hyaluronate, in a gel format, for as little as 3 days. 
2.3 
Mechanism of Action/Indication 
Sodium bicarbonate in a toothpaste has been shown to enhance the removal of plaque biofilms. 
Some of the proposed modes of action of sodium bicarbonate in toothpaste are; 
• The large crystals of sodium bicarbonate may help the toothbrush to physically displace 
plaque from the tooth surface. 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 1 9  of 7 7  
•  S o di u m bicar b o nate ma y re d uce t he visc osit y of t h e p ol ys acc hari de matri x w hic h hel ps 
bi n d t he bacteria t o get her a n d t o t he t o ot h s urface, res ulti n g i n easier pla q ue re m o val.  
S o di u m h yal ur o nate ( h yal ur o ni c aci d, 
H A) is a nat ur all y o cc urri n g p ol ysacc h ari d e 
( gl yc os a mi n o gl yca n) w hic h pla ys a r ole i n t he f u ncti o n of e xtracell ular matrices, i ncl u di n g 
t h ose of mi neralize d a n d n o n-mi nerali ze d peri o d o ntal tiss ues. T he s o di u m h ya l ur o n ate u n d er 
i n vesti gati o n i n t his pr oject is of hi g h m olec ul ar wei g ht (H M W; 2, 0 0 0, 0 0 0 Da). F or t he 
treat me nt of gi n gi vitis, its h y gr osc o pi c nat ure hel ps t o pr o vi de a n i m pr o ve d e n vir o n me nt i n 
w hic h t he b o d y ca n n at ur all y heal.  
I n relati o n t o oral healt h, a li mite d n u m ber of st u dies ha ve re p orte d o n t he efficac y of H M W 
s o di u m h yal ur o nat e i n t he oral e n vir o n me nt (i n gel, m o ut h was h a n d s pra y f or ms) i n t h e 
treat me nt of gi n gi vitis, wit h m ost e vi de nce base d o n t he gel f or mat ( 0. 2 % w/ w H M W s o di u m 
h yal ur o n ate) w h e n use d as a n a dj u nct t o re g ular t o ot h br us hi n g (
 
 
 
3  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  
T a bl e 3 -1  
St u d y O bj e cti v e s a n d E n d p oi nt s  
O bj e cti v e s  
E n d p oi nt s  
Pri m ar y  
T o e v al u at e t h e effi c a c y of a n e x p eri m e nt al 
d e ntifri c e c o nt ai ni n g 6 7 % w/ w s o di u m 
bi c ar b o n at e , 0. 2 % w/ w H M W s o di u m 
h y al ur o n at e  a n d 0. 2 2 1 % w/ w s o di u m fl u ori d e 
c o m p ar e d t o a fl u ori d e c o ntr ol d e ntifri c e, f or t h e 
a s s e s s m e nt of gi n gi viti s, a s  m e a s ur e d b y a 
Bl e e di n g I n d e x ( BI), aft er 6 w e e k s’ t wi c e d ail y 
t o ot h br u s hi n g. 
N u m b er ( n o. ) of bl e e di n g sit e s at 6 w e e k s.  
S e c o n d ar y  
T o e v al u at e t h e effi c a c y of a n e x p eri m e nt al 
d e ntifri c e c o nt ai ni n g 6 7 % w/ w s o di u m 
bi c ar b o n at e , 0. 2 % w/ w H M W s o di u m 
h y al ur o n a t e a n d 0. 2 2 1 % w/ w s o di u m fl u ori d e 
c o m p ar e d t o a 6 7 % w/ w s o di u m bi c ar b o n at e/ 
0. 2 2 1 % w/ w s o di u m fl u ori d e d e ntifri c e , f or t h e 
a s s e s s m e nt of gi n gi viti s, a s m e a s ur e d b y a 
Bl e e di n g I n d e x ( BI), aft er 6 w e e k s’ t wi c e d ail y 
t o ot h br u s hi n g. 
N u m b er ( n o. ) of bl e e di n g si t e s at 6 w e e k s. 
T o e v al u at e t h e effi c a c y of a  d e ntifri c e 
c o nt ai ni n g 6 7 % w/ w s o di u m bi c ar b o n at e / 
0. 2 2 1 % w/ w s o di u m fl u ori d e  c o m p ar e d t o a 
fl u ori d e c o ntr ol d e ntifri c e, f or t h e a s s e s s m e nt of 
gi n gi viti s, a s m e a s ur e d b y a Bl e e di n g I n d e x ( BI), 
aft er 6 w e e k s’ t w i c e d ail y t o ot h br u s hi n g. 
N u m b er ( n o. ) of bl e e di n g sit e s at 6 w e e k s .  
E x pl or at or y  
T o e v al u at e t h e effi c a c y of a n e x p eri m e nt al 
d e ntifri c e c o nt ai ni n g 6 7 % w/ w s o di u m 
N o. of bl e e di n g sit e s at 3 d a y s, 1 a n d 2 w e e k s.  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 20 of 77 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), over 2 weeks’ twice daily 
use. 
 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by a 
Bleeding Index (BI), over 6 weeks’ twice daily 
use. 
Mean BI at 3 days, 1, 2 and 6 weeks. 
 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of gingivitis, as measured by 
Modified Gingival Index (MGI), over 6 weeks 
twice daily use. 
Mean MGI at 3 days, 1, 2 and 6 weeks. 
To evaluate the efficacy of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride 
compared to a 67% w/w sodium bicarbonate/ 
0.221% w/w sodium fluoride dentifrice, with both 
compared to a fluoride control dentifrice, for the 
assessment of plaque accumulation, as 
measured by a Plaque Index (TPI; overall and 
interproximal), over 6 weeks twice daily use. 
Mean TPI (overall and interproximal) at 3 days, 
1, 2 and 6 weeks. 
To evaluate and compare MGI and mean BI in 
low (<45 bleeding sites) and high (>45 bleeding 
sites) BI subgroups following twice daily use of 
an experimental dentifrice containing 67% w/w 
sodium bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride, a 
67% w/w sodium bicarbonate/ 0.221% w/w 
sodium fluoride dentifrice and a fluoride control 
dentifrice, over 6 weeks twice daily use. 
Mean MGI and mean BI at 3 days, 1, 2 and 6 
weeks within each subgroup (low and high 
number of bleeding sites) 
Safety 
To assess the oral tolerability of an experimental 
dentifrice containing 67% w/w sodium 
bicarbonate, 0.2% w/w HMW sodium 
hyaluronate and 0.221% w/w sodium fluoride, a 
Treatment-emergent adverse events over 6 
weeks. 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 2 1  of 7 7  
6 7 % w/ w s o di u m bi c ar b o n at e / 0. 2 2 1 % w/ w 
s o di u m fl u ori d e  d e ntifri c e, a n d a fl u ori d e c o ntr ol 
d e ntifri c e o v er 6 w e e k s t wi c e d ail y u s e.  
T his P o P  st u d y will be c o nsi dere d s uccessf ul if t he e x peri me ntal de ntifrice c o ntai ni n g 6 7 % w/ w 
s o di u m bicar b o nate, 0. 2 % w/ w H M W s o di u m h yal ur o n ate  a n d 0. 2 2 1 % w/ w s o di u m fl u ori de  
de m o nstrates a re d u cti o n i n t he n u m ber of blee di n g sites c o mpare d t o a fl u ori de c o ntr o l 
de ntifrice.   
4  
S T U D Y D E SI G N  
4. 1  
O v er all D e si g n  
T his will be a si n gle -ce nter, e x a mi ner -bli n d, ra n d o mize d, stratifie d, t hree -treat me nt, parallel 
gr o u p, cli nical st u d y i n h ealt h y a d ult v ol u nteers wit h mil d t o m o derate gi n gi vitis.  T here will 
be si x visits t o t he st u d y site: Scree ni n g, Baseli ne, Da y 3 a n d Wee ks 1, 2 a n d 6. Gi n gi vitis will 
be assess e d usi n g a M GI (
) a n d a BI (
).  
Pla q ue will be assesse d b y t he T ures k y m o dificati o n of t he Q ui gle y Hei n (T PI ) (
 
). All e v al ua ble teet h (i n relati o n t o t he i ncl usi o n/ e x cl usi o n ge n eral de ntiti o n criteria) will 
be assesse d.  
Gi n gi vitis a n d pla q ue acc u m ulati o n will be gr ossl y assesse d at Scree ni n g  ( Visit 1; i n relati o n t o 
su bject scree ni n g ) a n d t he n f or mall y ass esse d ( M GI, BI & T PI) at m ulti ple ti me p oi nts acr oss 
t he 6-wee k treat me nt peri o d, f or all q ualif yi n g teet h at Baseli ne ( Da y 0 ) a n d t he n o n war ds ( Da ys 
3 , 7 , 14  a n d 42 ). A si n gle cli nical e x a mi ner will be res p o nsi ble f or t he c o n d uct of t he gi n gi vitis 
a n d pla q ue me as ures f or t he d ur ati o n of t he st u d y f or all s u bjects.  
At t he Scree ni n g visit ( Visit 1), s u bjects will gi ve t heir writte n i nf or me d c o nse nt t o partici pat e  
i n t he st u d y. D e m o gra p hi cs, me dical hist or y a n d c urre nt me dicati o ns will be rec or de d, f oll o we d 
b y a n oral e x a mi nati o n , a gi n gi val assess me nt. T his will i ncl u de a n O S T a n d O H T  e x a mi nati o n, 
de ntiti o n e x cl usi o ns a n d a gr oss gi n gi val assess me nt.  Uri ne pre g na n c y t esti n g f or all fe male 
s u bjects of re pr o d ucti ve p ote ntial will als o be perf or me d, t o e ns ure t hat pre g n a nt fe males are 
e x cl u de d fr o m t he st u d y.  
Wit hi n 1 0  t o 2 8 da ys of Scree ni n g ( Visit 1), eli gi ble s u bjects will ret ur n t o t he site f or t he 
Baseli ne visit ( Visit 2) wit h o ver ni g ht pla q ue (s u bjects will a bstai n fr o m oral h y gi e ne f or 1 2 hrs  
( + 6 hr; -2 hr) i.e. o ver ni g ht i m me diate l y b ef ore t he visit). At t he Baseli ne visit, s u bjects will 
u n der g o, i n t he f oll o wi n g or der, a f ull O S T a n d O H T e x a mi nati o n a n d assess me nts of gi n gi val  
i nfla m mati o n ( M GI), gi n gi val blee di n g ( BI) a n d s u pra-gi n gi val pla q ue ( T PI ). Uri ne pre g n a nc y 
testi n g f or all fe male s u bjects of re pr o d ucti ve p ote ntial will als o be perf or me d, t o e ns ure t hat 
pre g na nt fe males are e x cl u de d fr o m t he st u d y. Eli gi ble s u bjects will be stratifie d bas e d o n 
ge n d er a n d b aseli ne n u m ber of blee di n g sites  ( L o w: < 4 5 / Hi g h ≥ 4 5 blee di n g sites ), t o e ns ure a 
bala nce of gi n gi vitis acr oss treat me nt gr o u ps.  After t he Baseli ne assess me nts , a f ull de ntal 
pr o p h yla xis will be perf or me d f or eac h s u bj ect usi n g peri o d o ntal i nstr u m e nts a n d a sta n d ar d 
p olis hi n g de ntal  c o m p o u n d pr o p h yl a xis paste f oll o we d b y fl ossi n g b y t h e cli nicia n t o re m o v e 
s u b a n d s u pra-gi n gi val calc ul us, stai n, pla q ue a n d de bris fr o m t he teet h. S u bjects teet h will t he n 
be  re-discl ose d usi n g a discl osi n g s ol uti o n t o c hec k f or resi d ual pla q ue. A s ec o n d  cli nicia n will  
c hec k t o e ns ure all pla q ue has bee n re m o v e d. A n y resi d u al pla q ue re mai ni n g will be re m o ve d  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 2 2  of 7 7  
b y t h e cli nicia n as re q uire d a n d i ncl u di n g de ntal p olis hi n g wit h a sta n dar d p olis hi n g d e ntal  
c o m p o u n d, s uffici e nt t o bri n g t he s u bject t o zer o pla q ue  (i.e. T PI = 0). All s u bjects will e nter t h e 
treat me nt peri o d wit h n o visi ble pla q ue ( T PI = 0). S u bjects will be ra n d o mize d t o st u d y pr o d uct 
a n d t he n u n der g o a s u p er vise d br us hi n g, w here t he y will be i nstr ucte d t o br us h f or 1 ti me d 
mi n ute at site wit h t heir as si g ne d st u d y pr o d u ct, after w hic h t he y will be i nstr ucte d t o c o nti n u e 
usi n g t heir pr o d u ct t wice dail y  ( m or ni n g a n d e ve ni n g u ntil t heir ne xt visit). 
After usi n g t he st u d y d e ntifrice f or 3 da ys, 1, 2 a n d 6 wee ks, s u bjects will ret ur n t o t he st u d y,  
site ( Visits 3, 4, 5 a n d 6 res pecti vel y) wit h o ver ni g ht pla q ue (s u bjects will a bstai n fr o m 
o ver ni g ht t o ot h br us hi n g f or 1 2 hrs ( + 6 hr; -2 hr) i m me diatel y bef ore eac h assess me nt visit), at  
a p pr o xi matel y t he sa me ti me of da y as t he baseli ne visit. T he st u d y de ntifrice a n d  t he diar y will 
be re vie we d t o d eter mi ne treat me nt c o m plia nce. S u bjects will ha ve a f ull O S T e x a mi nati o n a n d  
t he n u n der g o, i n t he f oll o wi n g or der, M GI, BI a n d T PI ass ess me nts. At Visit 6, s u bjects will 
ret ur n all st u d y s u p plies a n d ha ve a d e ntal pr o p h yl a xis if dee me d a p pr o priate b y t he i n v esti gat or 
or e x a mi ner.  
At Visits 2, 3, 4, 5 a n d 6, re peata bilit y dat a will be ge nerate d f or M GI a n d T PI assess me nts 
fr o m re plicate e x a mi nati o ns o n t he sa me s u bject. De pe n di n g o n s u bject visit sc he d uli n g, e ver y 
eff ort will be ma d e t o c o m plete o ne re p eata bilit y e x a mi nati o n f or eac h cli nical meas ure d uri n g 
eac h cli nical sessi o n, t hat is, at least o ne i n t he m or ni n g a n d at least o ne i n t he after n o o n o n 
eac h assess me nt da y. Re p eata bilit y e x a mi nati o ns will be se parate d b y a mi ni m u m of 1 0 mi n utes 
a n d, w here p ossi ble, se parate d b y a n ot h er s u bj ect. D ue t o t he i n vasi v e nat ur e of t he BI 
assess me nt, it is n ot feasi ble t o c o n d uct a n acc urat e re peata bilit y assess me nt f or t his i n de x.  
A d verse e v e nts a n d i nci de nts will be rec or de d fr o m i nf or me d c o nse nt a n d at t he e n d of eac h 
st u d y visit. 
4. 2  
R ati o n al e f or St u d y D e si g n  
T he mai n ai m of t his pr o of -of -pri nci ple cli nical st u d y is t o e v al uate t he efficac y of a n 
e x peri me ntal de ntifrice c o ntai ni n g 6 7 % w/ w s o di u m bicar b o nate , 0. 2 % w/ w H M W s o di u m 
h yal ur o n a te a n d 0. 2 2 1 % w/ w s o di u m fl u ori de a gai nst a refere nce re g ular fl u ori de de ntifri ce t o 
c o ntr ol gi n gi vitis ( gi n gi val blee di n g a n d vis u al si g ns of gi n gi v al i nfla m mati o n) i n de ntall y a n d 
peri o d o ntall y h ealt h y a d ult v ol u nteers wit h mil d -m o derate gi n gi vitis o ver 6 wee ks’ us e.  
T his desi g n is t y pic al of ma n y st u dies c o n d ucte d  t o e val uate t he cli nical efficac y of de ntifrices 
i n t he treat me nt of gi n gi vitis (
). St u d y s u bjects wit h a pre -s pecifie d le vel of 
gi n gi vitis are ra n d o mi ze d t o st u d y pr o d uct; efficac y is deter mi ne d aft er pr ofessi o nal de ntal 
clea ni n g a n d a peri o d of t wice -dail y br us hi n g, c o m pare d t o a c o ntr ol/c o m para t or de ntifri ce.  
Healt h y s u bj ects wit h mil d -m o derate gi n gi vitis will be i ncl u de d i n t he st u d y p o p ulati o n. T he 
defi ne d le v el of gi n gi vitis at bas eli ne, will hel p t o mi ni mize t he ris k of a n at y pical or p ote ntial 
lac k of treat me nt res p o nse f or s u bjects wit h hi g h le vels of gi n gi vitis t hat ma y ot her wise b e 
ma na ge d pr ofessi o nall y rat her t ha n s olel y via h o me use of a t wice d ail y de ntifrice. F urt her m ore, 
s u bjects will be stratifie d base d o n ge n d er a n d b aseli ne n u m ber of blee di n g sites t o e ns ure a  
bala nce i n tr eat me nt gr o u ps  acr oss gi n gi vitis a n d ge n der , a n d gi ve n t hat ge n d er is a k n o w n 
m o difier of t he i nitiati o n a n d o utc o me of c o n diti o ns relati n g t o gi n gi v al healt h , gi ve n t hat 
h or m o nal fl uct uati o ns t hr o u g h t he fe male me nstr ual c ycl e ma y als o i nfl ue nce res p o nse t o  de ntal 
pla q ue a n d lea d t o i ncrease d vari a bilit y i n t he  cli nical assess me nt of gi n gi val healt h  (
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 2 3  of 7 7  
). Stratif yi n g b y n u m ber of blee di n g sites at bas eli ne will als o facilitate 
e val uati o n of gi n gi vitis i n l o w a n d hi g h gi n gi vitis ( n u m ber of blee di n g sites) s u b gr o u ps.  
T he M GI a n d t he BI are esta blis he d cli nical meas ures of gi n gi val i nfla m mati o n a n d gi n gi val 
blee di n g, res pecti vel y  (i. e. gi n gi val h ealt h); t he T PI is a n esta blis he d  cli nical meas ure of s u pra -
gi n gi val pla q u e acc u m ul ati o n.  A si n gle cli nical e x a mi ner will b e res p o nsi ble f or t he  c o n d uct of 
t he gi n gi vitis a n d pla q ue acc u m ulati o n meas ures (t he sa me e x a mi ner bei n g a ble t o c o n d uct all 
gi n gi vitis/ pla q ue assess me nts) f or t h e d urati o n of t he st u d y f or all  s u bjects, t o eli mi nate t h e 
p ossi bilit y of i nter -e x a mi ner vari a bilit y.  
T o assess e x a mi ner re pr o d uci bilit y acr oss t he treat me nt peri o d, re peat 
M GI a n d T PI 
assess me nts will be perf or me d o n selecte d s u bjects t hr o u g h o ut t he st u d y. D ue t o t he i n vasi ve 
nat ure  of t he i n d e x, re peata bilit y assess me nts are n ot feasi ble f or t h e BI.  
A parallel gr o u p desi g n h as bee n sele cte d as m ost a p pr o priate f or t his i n vesti gati o n. A ntici pate d 
differe ntial c h a n ges i n cli nical varia bles a m o n g treat me nt gr o u ps c o u l d lea d t o carr y o ver effects 
a n d a n altere d oral heat h state s h o ul d a cr oss o ver desi g n b e e m pl o ye d. T he d osa ge re gi me n of 
t wice dail y use ( m or ni n g a n d e ve ni n g) will be t he sa me f or eac h treat me nt gr o u p a n d is base d 
o n c o ns u mer ha bit a n d c o m m o n practice wit hi n oral care cli nical tri als.  
T he d osa ge re gi me n of t wice dail y treat me nt ( m or ni n g a n d e ve ni n g) f or t h e was h o ut  de ntifrice  
a n d st u d y pr o d ucts will be t he s a me f or all s u bjects, a n d is bas e d o n wi del y rec o m me n d e d oral  
h y gie n e practice, a n d t y pical c o ns u mer  h a bit. T o facilitate c o m plia nce wit h pr o d uct usa ge  
t hr o u g h o ut t he st u d y, a n d t o e na ble staff t o c o nfir m c orrect d osi n g, a s u per vise d br us hi n g will 
be perf or me d o n site at t he e n d of Visits 1 -5 ; s u bj ects will be re q uire d t o rec or d eac h br us hi n g 
i n t he diary pr o vi de d , i ncl u di n g t he ti me of last br us hi n g pri or t o ret ur ni n g f or t he site 
assess me nt visits.  
D uri n g t he was h o ut  peri o d f or t his st u d y  (mi ni m u m 1 0  da ys/ ma xi m u m 2 8 da ys ), eli gi bl e 
s u bjects will use a m ar kete d, re g ular fl u ori de t o ot h paste a n d t o ot h br us h (as pr o vi de d). Us e of 
t hese pr o d ucts will sta n dar dize t he st u d y p o p ulati o n’s oral h y gi e ne re gi me n pri or t o t he Bas eli ne 
visit a n d hel p fa miliarize s u bjects wit h  t h e d osi n g/ diar y c o m pleti o n re q uir e me nts. It will als o 
ser ve as a ‘ was h o ut’ fr o m a n y a nti-pla q ue  i n gre die nts c o ntai ne d i n t he s u bject’s o w n oral 
h y gie n e pr o d ucts a n d all o w t he gi n gi vae ti me t o  rec o ver pri or t o Bas eli ne ass ess me nt of gi n gi val 
blee di n g (f oll o wi n g peri o d o ntal pr o bi n g at  Scree ni n g).  
T he c h oice of ti me p oi nts relates t o p u blis he d a nti -gi n gi vitis efficac y f or a 6 7 % w/ w s o di u m 
bicar b o nate de ntifri ce aft er 6 wee ks of t wi ce d ail y us e, al o n g wit h earlier ti me p oi nts relati n g 
t o p u blis he d e vi de nce of i m pr o ve d gi n gi val healt h wit h a dj u ncti ve use of s o di u m h yal ur o nate, 
i n a gel f or mat, f or as little as 3 da ys.  
A  mi ni m u m of 2 0 per ma ne nt gra d a ble teet h is si milarl y i n a gree me nt wit h G S K C H gi n gi vitis  
cli nical st u dies a n d bei n g re prese ntati ve of a mi ni m u m of a “s h orte n e d de ntal arc h ” (
 
) e q uati n g t o a n y w h ere b et wee n 2 0 -2 8 gra d a ble teet h (e x cl u di n g 3r d m olars). Wit h 6 sites  
e x a mi ne d per t o ot h f or t h e blee di n g i n de x (
), e q uati n g t o 1 2 0-
1 6 8 blee di n g sites meas ure d, a mi ni m u m of 2 0 blee di n g sites at Baseli ne i n cl usi o n criteria als o  
re pres e nts a mi ni m u m of ~ 1 2 % blee di n g sites w hic h is i n a gree me nt wit h t he c o nse ns us re p ort 
of w or k gr o u p 1 of t he 2 0 1 7 W orl d W or ks h o p o n t he Classificati o n of Peri o d o ntal a n d Peri -
I m pla nt Diseas es a n d C o n diti o ns (
). F urt her m ore, t he bas eli ne le vels of 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 2 4  of 7 7  
meas ures of gi n gi vitis a n d pla q ue a gree wit h pre vi o us G S K C H gi n gi vitis st u dies i ncl u di n g 
t h ose i n vesti gati n g a s o di u m bicar b o nate c o ntai ni n g d e ntifrice wit h mea n 
M GI 1. 7 5-2. 3 0 
c o nsi dere d re prese ntati ve of ge neralise d mil d -m o derate gi n gi vitis.  
A de ntal pr o p h yl a xis is  i ncl u de d as t his is c o nsi dere d i n d ustr y sta n d ar d i n a gree me nt wit h F D A 
g ui deli nes  (
), is i n a gree ment wit h pre vi o us G S K C H gi n gi vitis  cli nical st u dies, 
al o n g wit h  a lac k of de ntal calc ul us/ stai ni n g w hic h  c o ul d ot her wise acts as p la q ue rete nti v e 
fact ors f or s u bjects partici pati n g i n t he cli nical st u d y.  
T he ne gati ve c o ntr ol de ntifrice ( Crest Ca vit y Pr ot ecti o n)  a n d t he 6 -wee k u p per ti me p oi nt are 
c o nsi dere d i m p ort a nt i n relati o n t o bei n g a ble t o c o m pare wit h pre vi o us G S K data wit h t he 6 7 % 
w/ w s o di u m bicar b o nate f or m ulati o n wit h 6 wee ks as t he s h ortest ti me p oi nt ( 2 4 -wee k st u dies; 
(
)). 
T he c o m p aris o n of t he e x peri me ntal de ntifrice c o ntai ni n g 6 7 % w/ w s o di u m bicar b o nate, 0. 2 % 
w/ w H M W s o di u m h yal ur o nate a n d 0. 2 2 1 % w/ w s o di u m fl u ori de t o t he ne gati ve c o ntr ol has 
bee n c h ose n as  t he pri mar y o bj ecti ve gi v e n t hat t his is t he mi ni m u m re q uir e me nt t o de m o nstrat e 
st u d y s uccess i n relati o n t o perf or ma nce i n pl a q ue/ gi n gi vitis efficac y. F oll o wi n g t his, a 
c o m paris o n bet wee n t he e x peri me ntal de ntifrice t o a 6 7 % w/ w s o di u m bicar b o nate / 0. 2 21 % 
w/ w s o di u m fl u ori de  de ntifrice ( mi n us t he 0. 2 % w/ w  H M W  s o di u m h yal ur o nate) as a p ositi ve 
c o ntr ol wit h a nti -gi n gi vitis efficac y a n d all o wi n g c o m paris o n i n relati o n t o t he effect of a d diti o n 
of H M W s o di u m h yal ur o nate i n t he e x peri me ntal de ntifrice f or m ulati o n, t here b y all o wi n g 
a d diti o nal be nc h mar ki n g o n perf or ma n ce .  
H or m o nal c ha n ges d uri n g pre g na nc y m a y affect t he res p o nse of t he gi n gi val tiss ue t o pla q ue 
bacteria a n d c o ul d i m pact t he gi n gi vitis efficac y meas ure m e nts (
). T heref ore, 
w o me n w h o are pre g na nt at scree ni n g will be e x cl u de d a n d w o ma n w h o bec o me pre g na nt 
d uri n g t he c o urse of t he st u d y will be disc o nti n ue d. It s h o ul d be n ote d h o we ver, t hat t here are 
n o safet y c o ncer ns wit h pre g na nt w o me n usi n g a n y of t he st u d y pr o d uct s. P re g n a nc y testi n g 
will als o be u n derta ke n as a preca uti o n, gi v e n t hat t here are c urre ntl y n o p u blis he d cli nical dat a 
i n vesti gati n g t he efficac y of H M W s o di u m h yal ur o nate i n a t o ot h paste f or t he tr eat me nt of 
gi n gi vitis , pl us t hat pre g n a nc y is k n o w n t o i nfl ue n ce peri o d o ntal stat us (
 
), a n d t heref ore p ote ntiall y i nfl ue nci n g t he efficac y meas ures i n t his st u d y. 
Pre g n a nc y testi n g at b ot h scree ni n g a n d baseli ne will e ns ure n o pre g na nt w o me n will recei ve 
st u d y pr o d uct. 
T he effects of s m o ki n g o n peri o d o ntal healt h are well d oc u me nte d i n t he scie ntific literat ure.  
S m o ki n g decreases bl o o d fl o w wit hi n t he gi n gi val micr o vasc ul at ure a n d i nterferes  wit h  
ne utr o p hil f u ncti o n, s u p pressi n g t he i nfla m mat or y res p o nse t o d e ntal pla q ue a n d mas ki n g t h e  
cli nical si g ns of peri o d o ntal disease (
). A 1 4-d a y  
e x peri me ntal gi n gi vitis m o del re p orte d m uc h l ess gi n gi val blee di n g i n s m o kers c o m pare d t o  
n o n -s m o kers, e ve n t h o u g h pla q ue le vels a n d t h e c o m p ositi o n of t he oral micr ofl ora were si mil ar  
bet wee n t h e t w o gr o u ps (
). S m o kers will t heref ore be e x cl u de d fr o m t his 
i n vesti gati o n of pr o d u ct efficac y f or t he treat me nt of pla q ue-i n d uce d gi n gi vitis. 
Acc or di n g t o t he I nter n ati o nal C o nfere nce o n Har m o nizati o n of Tec h nical Re q uire me nts f or  
Re gistrati o n of P har mace uticals f or H u ma n Us e (I C H) g ui deli nes, f or a st u d y t o be cla ssifie d 
as tr ul y d o u ble -bli n d, n ot o nl y d oes t he e x a mi ner (a n d a n y a p pr o priate me m ber of staff w h o  
ma y be i n v ol ve d i n t he dis pe nsi n g of pr o d ucts, a nal ysis of data etc.) nee d t o be bli n de d as t o  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI
C CI
C CI

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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 this oral care study, the level of 
blindness for this study is described as “examiner blind”.  
4.3 
Justification for Dose 
The study products are dentifrices, intended for topical oral use, and will be applied by 
toothbrushing using a manual toothbrush. 
The dosage regimen of twice daily treatment (morning and evening) will be the same for all 
subjects and is based on widely recommended oral hygiene practice/typical consumer habit. 
Study subjects will be instructed to brush for at least 1 timed minute with their assigned study 
dentifrice on each brushing occasion. After 6 weeks (Day 42±3 days) twice daily treatment, 
each subject should complete between approximately 84-90 treatment applications. 
Each subject will complete a supervised brushing with their assigned study dentifrice at the end 
of each study visit (while still at the study site) to enable staff to check correct dosing and 
encourage compliance with product usage throughout the study. 
4.4 
End of Study Definition 
A subject is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities. 
The end of this study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last subject in the trial.  
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
Sufficient subjects will be screened (approximately 160 subjects) to randomize 120 to ensure 
108 evaluable subjects complete the entire study.  
An enrolled subject is one who has agreed to participate in the clinical study following 
completion of the informed consent process directly or via their legally authorized 
representative and successfully met eligibility criteria to proceed beyond the screening visit as 
applicable for the protocol design.  
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether a subject is suitable for this protocol.   
Subject eligibility to participate in the clinical study should be reviewed and documented by an 
appropriate member of the investigator’s study team before subjects are included in the study. 
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5.2 
Inclusion Criteria 
An individual must meet all the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Subject provision of a signed and dated informed consent document indicating that the 
subject has been informed of all pertinent aspects of the study before any assessment is 
performed. 
2. Subject is male or female who, at the time of screening, is between the ages of 18 to 65 
years, inclusive. 
3. A subject who is willing and able to comply with scheduled visits, treatment plan, and other 
study procedures. 
4. A subject in good general and mental health with, in the opinion of the investigator or 
medically qualified designee, no clinically significant/relevant abnormalities in medical 
history or upon oral examination, or condition, that would impact the subject’s safety, 
wellbeing or the outcome of the study, if they were to participate in the study, or affect the 
individual’s ability to understand and follow study procedures and requirements. 
5. A female subject of childbearing potential must have negative pregnancy test results at 
screening and baseline.  
6. A female subject of childbearing potential and at risk for pregnancy must agree to use a 
highly effective method of contraception throughout the study and for 5 days after the last 
dose of assigned treatment.  A female subject who is of childbearing potential must meet 
requirements in Section 5.5.4. 
7. AT SCREENING (Visit 1): 
a. A subject with at least 20 natural, permanent teeth. 
b. A subject with at least 40 evaluable surfaces for MGI, BI and TPI.  
An evaluable surface is defined as having 2/3rds of the natural tooth surface gradable 
for the selected clinical indices. The following should not be included in the evaluable 
surface count- third molars; fully crowned/extensively restored, grossly carious, 
orthodontically banded/bonded or abutment teeth; surfaces with calculus deposits 
which, in the opinion of the clinical examiner, would interfere with the baseline 
assessments of the selected clinical indices. 
c. A subject with generalized mild- moderate plaque-induced gingivitis, in the opinion of 
the clinical examiner, as confirmed by a gross visual examination at the Screening Visit. 
8. AT BASELINE – Prior to Dental Prophylaxis (Visit 2): 
a. A subject with ongoing hard tissue eligibility and, in the opinion of the clinical 
examiner, at least 40 evaluable surfaces. 
b. A subject with mean whole mouth MGI between 1.75 and 2.30. 
c. A subject with mean whole mouth TPI score ≥1.5. 
d. A subject with a minimum of 20 bleeding sites. 
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5.3 
Exclusion Criteria 
An individual who meets any of the following exclusion criteria will not be eligible for 
enrollment into the study: 
1. A subject who is an employee of the investigational site, either directly involved in the 
conduct of the study or a member of their immediate family; or an employee of the 
investigational site otherwise supervised by the investigator; or, a GSKCH employee 
directly involved in the conduct of the study or a member of their immediate family. 
2. A subject who has participated in other studies (including non-medicinal studies) involving 
investigational product(s) within 30 days prior to study entry and/or during study 
participation. 
3. A subject with, in the opinion of the investigator or medically qualified designee, an acute 
or chronic medical or psychiatric condition or laboratory abnormality that may increase the 
risk associated with study participation or investigational product administration or may 
interfere with the interpretation of study results and, in the judgment of the investigator or 
medically qualified designee, would make the subject inappropriate for entry into this study. 
4. A subject with any other clinical serious or unstable conditions (e.g. cardiovascular diseases, 
diabetes, liver disorders and kidney disorders) which may affect study outcomes and/ or 
subject safety.  
5. A subject who is a pregnant female (including a woman who has a positive urine pregnancy 
test; pregnancy testing will be carried out for all female subjects who are of child bearing 
potential) or is intending to become pregnant over the duration of the study.  
6. A subject who is a breastfeeding female. 
7. A subject with known or suspected intolerance or hypersensitivity to the study materials (or 
closely related compounds) or any of their stated ingredients. 
8. A subject unwilling or unable to comply with the Lifestyle Considerations described in this 
protocol.  
9. Subject who is a current smoker or an ex- smoker who stopped within 6 months of Screening. 
10. Subject who currently uses smokeless forms of tobacco (e.g. chewing tobacco, gutkha, pan 
containing tobacco, nicotine-based e-cigarettes). 
11. A subject with diagnosed xerostomia or taking any medication that in the view of the 
investigator causes xerostomia.  
12. A subject with a medical condition which may directly influence gingival bleeding.  
13. A subject with a bleeding disorder that may affect study outcomes and/ or subject safety. 
14. Recent history (within the last year) of alcohol or other substance abuse. 
15. A subject with a severe oral condition (e.g. acute necrotizing ulcerative gingivitis or oral or 
peri-oral ulceration including herpetic lesions) that would, in the opinion of the investigator, 
compromise study outcomes or the oral health of the subject/ examiner if they were to 
participate in the study.  
16. Presence of a tongue or lip piercing, or any other oral feature that could interfere with the 
usage of a toothbrush. 
17. Medication Exclusions  
AT SCREENING (Visit 1): 
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a. A subject currently taking antibiotics or requiring antibiotic use prior to dental 
prophylaxis or other dental procedures. 
b. A subject currently taking an anti-inflammatory medication which, in the opinion of the 
Investigator, could affect gingival condition. 
c. A subject currently taking a systemic medication (e.g. anti-inflammatory, anti-coagulant, 
immunosuppressants) or traditional/ herbal remedy which, in the opinion of the 
Investigator, could affect plaque/ gingival condition (e.g. ibuprofen, aspirin, warfarin, 
cyclosporin, phenytoin, calcium channel blockers).  
18. Medication exclusions  
AT BASELINE (Visit 2): 
a. A subject who has taken (in the previous 14 days), any antibiotics.  
b. A subject who has taken (in the previous 14 days) a systemic medication (e.g. anti-
inflammatory, anti-coagulant, immunosuppressants) or traditional/ herbal remedy 
which, in the opinion of the Investigator, could affect plaque/ gingival condition (e.g. 
ibuprofen, aspirin, warfarin, cyclosporin, phenytoin, calcium channel blockers). 
c. A subject who has used an antibacterial dentifrice or mouthwash (e.g. chlorhexidine) or 
any oral care product that in the view of the investigator could interfere with plaque 
formation or measures of gingivitis, in the period between Screening and the Baseline 
visit.  
19. Periodontal Exclusions 
a. A subject with signs of active periodontitis. 
b. Subject with gingivitis which, in the opinion of the investigator, is not expected to 
respond to treatment with an over-the-counter dentifrice. 
c. A subject who is receiving or has received treatment for periodontal disease (including 
surgery) within 12 months of Screening. 
20. Dental Exclusions 
a. A subject with active caries that could, in the opinion of the investigator, compromise 
study outcomes or the oral health of the subject if they were to participate in the study. 
b. A subject with dentures (partial or full). 
c. A subject with an orthodontic appliance (bands, appliances or fixed/ removable 
retainers). 
d. A subject who has received orthodontic therapy within 12 months of Screening. 
e. A subject with numerous restorations in a poor state of repair. 
f. A subject with any dental condition (e.g. overcrowding) that could, in the opinion of the 
investigator, compromise study outcomes or the oral health of the subject if they were 
to participate in the study. 
g. A subject who has had dental prophylaxis within 12 weeks of Screening. 
h. A subject who has had teeth bleaching within 12 weeks of Screening. 
i. A subject with high levels of extrinsic stain or calculus deposits that might interfere 
with plaque assessments. 
21. A subject who has previously been enrolled in this study. 
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22. A subject who, in the opinion of the investigator or medically qualified designee, should not 
participate in the study. 
5.4 
Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.  
Subjects will be stratified based on gender (male/ female), and baseline number of bleeding 
sites (low: <45 bleeding sites; high: ≥45 bleeding sites).  
The stratification factor will give rise to 4 strata. 
• Stratum 1: Male, Baseline number of bleeding sites <45. 
• Stratum 2: Male, Baseline number of bleeding sites ≥45. 
• Stratum 3: Female, Baseline number of bleeding sites <45. 
• Stratum 4: Female, Baseline number of bleeding sites ≥45. 
Subjects will be allocated to one of four strata and within each stratum, randomization numbers 
will be assigned in ascending numerical order as each subject is determined to be fully eligible. 
5.5 
Lifestyle Considerations 
5.5.1 
Dental Product/Treatment and Oral Hygiene Restrictions 
From Screening (Visit 1) to the Subject’s Last Study Visit 
• Subjects should not use any other oral care products (e.g. dentifrices, toothbrushes, 
mouthrinses) other than those provided during the study. 
• Subjects should not carry out any interproximal dental cleaning. Use of dental floss, 
toothpicks, waterpicks or inter-dental brushes is prohibited (except for the removal of 
impacted food with non-antimicrobial products only). 
• Subjects should delay any non-emergency dental treatment until after study 
completion (including dental prophylaxis). 
Before Clinical Efficacy Assessment Visits: Baseline (Visit 2) to Last Study Visit 
• Subjects should refrain from oral hygiene procedures for 12 hours ((+6hr, -2hr) before 
their visit and attend the study site with overnight plaque growth. 
5.5.2 
Dietary and Smoking Restrictions 
From Screening (Visit 1) to the Subject’s Last Study Visit 
• Subjects should not chew gum or consume any confectionery containing xylitol (e.g. 
mints). 
• Subjects must abstain from smoking/ use of tobacco products (e.g. chewing tobacco, 
gutkha, pan containing tobacco, nicotine-based e-cigarettes). 
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Before Clinical Efficacy Assessment Visits: Baseline (Visit 2) to Last Study Visit 
• Subjects must abstain from all food and drink (except water) for at least 4hrs prior to 
their scheduled assessment visits and until all assessments are complete during visit 
days. Water is permitted until 1 hour prior to their scheduled study visits.  
5.5.3 
Medication and Treatment Restrictions 
The following medication and treatment restrictions apply for the duration of the study: 
• If current/ concomitant medications/ treatments or traditional herbal ingredients/ 
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.  
For more information on concomitant medications, please refer to Section 6.8. 
5.5.4 
Contraception 
All female subjects who are of childbearing potential and are sexually active and at risk for 
pregnancy must agree to use a highly effective method of contraception consistently and 
correctly for the duration of the active study period and for at least 5 days after the last dose of 
investigational product.  
Female subjects of non-childbearing potential must meet at least one of the following criteria 
(subject-reported): 
• Female who has achieved post-menopausal status, defined as cessation of regular 
menses for at least 12 consecutive months with no alternative pathological or 
physiological cause; 
• Female who has undergone a documented hysterectomy and/or bilateral oophorectomy; 
• Female who has undergone one of the following procedures: bilateral tubal ligation or 
salpingectomy; hysteroscopic tubal occlusion procedure with follow-up confirmation of 
bilateral tubal occlusion. 
The investigator or his or her designee will discuss with the subject the need to use highly 
effective contraception consistently and correctly according to the schedule of activities and 
document such conversation.  In addition, the investigator or his or her designee will instruct 
the subject to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the subject or the subject’s partner.  
The following is the all-inclusive list of the highly effective methods for avoiding pregnancy 
that meets the GSK definition (i.e., have a failure rate of less than 1% per year when used 
consistently and correctly and, when applicable, in accordance with the product label).  
The list does not apply to females of reproductive potential with same sex partners or for 
subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long 
term and persistent basis, when this is their preferred and usual lifestyle. Periodic abstinence 
(e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception. 
1. Contraceptive subdermal implant 
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2. Intrauterine device (IUD) or intrauterine system 
3. Combined estrogen and progestogen oral contraceptive  
4. Injectable progestogen  
5. Contraceptive vaginal ring  
6. Percutaneous contraceptive patches  
7. Male partner sterilization ≥3 months prior to taking part in the study, or documentation 
of a 0 sperm count/azoospermia prior to the female subject's entry into the study, and 
this male is the sole partner for that subject. The documentation on male sterility can 
come from site personnel review of subject’s medical records, medical examination 
and/or semen analysis, or medical history interview provided by her or her partner. 
These allowed methods of contraception are only effective when used consistently, correctly 
and in accordance with the product label. An IUD must be in use at least 30 days prior to first 
study drug administration and barrier methods must be in use at least 14 days prior to study 
drug administration. 
The investigator is responsible for ensuring that subjects understand how to properly use these 
methods of contraception. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. To ensure transparent reporting of screen failure subjects, a 
minimal set of screen failure information will include demography, screen failure details (e.g. 
withdrawal of consent, eligibility criteria, and any adverse events or incidents as applicable.)  
Individuals who do not meet the criteria for participation in this study (screen failure) may not 
be re-screened. 
5.7 
Sponsor’s Qualified Medical Personnel 
Contact information for the sponsor's appropriately qualified medical/dental personnel for the 
study is documented in the Study Contact List located in the investigator study master file held 
at the study site. 
The contact number is only to be used by investigational staff seeking advice on medical/ dental 
questions or problems in the event that the established communication pathways between the 
investigational site and the study team are not available.   
The contact number is not intended for direct use by study subjects.  To facilitate access to 
appropriately qualified medical/dental personnel on study-related medical/dental questions or 
problems, subjects will be provided with a contact card.  The contact card will provide, as a 
minimum, protocol identifiers, the subject’s study identification number, contact information 
for the investigational site, and contact details in the event that the investigational site cannot 
be reached to provide advice on a medical question or problem identified by a healthcare 
professional other than the investigator.   
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 3 2  of 7 7  
5. 8  
R at er/ Cli ni c al A s s e s s or Q u alifi c ati o n s  
Cli nical e x a mi ners i n v ol ve d i n scree ni n g a n d effi cac y assess me nt pr oce d ures will b e  q ualifi e d 
de ntal pr ofessi o nals , re gistere d t o practice i n Ca na da. Oral e x a mi nati o ns t o deter mi ne s u bject 
eli gi bilit y a n d all safet y a n d effic ac y ( M GI, BI & T PI) assess me nts will be perf or me d b y a n 
a p pr o priatel y trai ne d cli nical e x a mi ner  wit h a d e m o nstra ble rece nt hist or y of use of t h ese 
meas ures i n cli nical trials . 
6  
I N V E S TI G A TI O N A L/ S TU D Y P R O D U C T S  
F or t he p ur p oses of t his st u d y, per I nter nati o nal C o nfere n ce o n Har m o nizati o n (I C H) g ui d eli nes, 
a n d G S K p olic y, i n vesti gati o nal pr o d uct is defi ne d as a p har mace utical f or m of a n acti ve 
i n gre di e nt, a n o n-me di ci nal pr o d uct ( mar kete d or i n vesti ga ti o nal), or a place b o, bei n g teste d or 
use d as a refere n ce ( p ositi ve or ne gati ve c o ntr ol), i n a cli nical trial. T his i ncl u des a pr o d uct wit h 
a mar keti n g a ut h orizati o n w he n use d or asse m ble d (f or m ulate d or pac k a ge d) i n a wa y differe nt 
fr o m t he a p pr o ve d f or m, or w he n use d f or a n u n a p pr o ve d i n dicati o n, or w he n use d t o gai n 
f urt her i nf or m ati o n a b o ut a n a p pr o ve d use.  
6. 1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
T he f oll o wi n g st u d y pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:  
T a bl e 6 -1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
 
W a s h o ut  
Pr o d u ct  
E x p eri m e nt al 
Pr o d u ct  
P o siti v e c o ntr ol  
N e g ati v e c o ntr ol  
Pr o d u ct N a m e  
D e ntifri c e 
c o nt ai ni n g 
1 0 0 0 p p m fl u ori d e 
a s S M F P ( C ol g at e  
C a vit y Pr ot e cti o n)  
E x p eri m e nt al 
d e ntifri c e 
c o nt ai ni n g 6 7 % 
w/ w s o di u m 
bi c ar b o n at e, 0. 2 % 
w/ w s o di u m 
h y al ur o n at e a n d 
0. 2 2 1 % w/ w  
s o di u m fl u ori d e  
D e ntifri c e 
c o nt ai ni n g 6 7 % 
w/ w s o di u m 
bi c ar b o n at e a n d 
0. 2 2 1 % w/ w 
s o di u m fl u ori d e  
D e ntifri c e 
c o nt ai ni n g 
1 1 0 0 p p m fl u o ri d e 
a s s o di u m fl u ori d e 
( Cr e st C a vit y 
Pr ot e cti o n)  
Pr o d u ct 
M a st er 
F or m ul ati o n 
C o d e ( M F C)  
C a n a di a n 
m ar k et e d pr o d u ct  
( N P N n o. 
) 
 
 
( N P N n o. 
) 
C a n a di a n 
m ar k et e d pr o d u ct  
(
) 
D o s e/  
A p pli c ati o n  
F ull ri b b o n of t o ot h p a st e t o c o v er t h e h e a d of t o ot h br u s h pr o vi d e d  
R o ut e of 
A d mi ni str ati o n  
Or al t o pi c al  
U s a g e 
I n str u cti o n s 
S u bj e ct s will br u s h t h eir t e et h f or o n e ti m e d mi n ut e t wi c e a d a y ( m or ni n g a n d 
e v e ni n g)  
R et ur n 
R e q uir e m e nt s  
All u s e d/ u n u s e d s a m pl e s  t o b e r et ur n e d 
T a bl e 6 -2  
S u n dr y It e m s  
S u n dr y Ite ms t o be s u p plie d:  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI
C CI
C CI
C CI

GSK Consumer Healthcare 
 
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Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Item 
Supplied 
By 
Pack Design 
Dispensing 
Details 
Return/Disposal Details 
Used 
Samples 
Unused 
Samples 
Oral-B Sensi-soft 
manual toothbrush 
(Canadian market) 
GSK CH 
Individual 
toothbrush in 
commercial 
pack 
One toothbrush at 
Screening for use 
with Lead-In 
product & one 
toothbrush at 
Baseline for use 
with assigned study 
dentifrice 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Countdown Timer 
GSK CH 
Individual 
timer in 
commercial 
pack 
One timer at 
Screening visit 
Subject to 
keep or 
destroyed at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Pregnancy Test Kits 
(Canadian market) 
GSK CH 
Commercial 
pack 
Not dispensed to 
subjects; only used 
at study site. Use 
as per study 
schedule 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Dosing Cups 
GSK CH 
Commercial 
pack 
Not dispensed to 
subjects; only used 
at study site. 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Opaque bags 
GSK CH 
Commercial 
pack 
Screening visit; 
Baseline visit; Visits 
3, 4, 5 & 6 (Days 3, 
7, 14 & 42 
respectively) 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Chrom-O-Red plaque 
disclosing solution 
(Canadian marketed 
product) 
Site 
Commercial 
pack 
Not dispensed to 
subjects; only used 
at study site. Use 
as per commercial 
label and study 
schedule 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Non-antimicrobial 
dental floss 
Site 
Commercial 
pack 
Not dispensed to 
subjects; only used 
at study site. Use 
as per commercial 
label and study 
schedule 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
Prophylaxis paste 
Site 
Commercial 
pack 
Not dispensed to 
subjects; only used 
at study site. Use 
as per commercial 
label and study 
schedule 
Destroy at 
site using 
site disposal 
procedures 
Return to 
3rd party 
vendor 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 34 of 77 
For further information, please refer to the Global Clinical Supplies (GCS) Packaging and 
Labelling Proposal. 
Detailed instructions for the disposal of study product/study supplies for the accountability 
checks and subsequent destruction will be provided by GSK CH during the study in time for 
study close out visit. 
6.1.1 
Dosage Form and Packaging 
The experimental and positive control dentifrices will be manufactured and filled into plain 
white tubes and supplied by GSK CH. The washout and negative control dentifrices will be 
sourced from the Canadian market.  
All dentifrices will be presented to the clinical study site in tubes that have been overwrapped 
in white vinyl to obscure any branding on the commercial packs with a study label affixed. The 
contents of the label will be in accordance with all applicable regulatory requirements and will 
be the responsibility of the Global Clinical Supplies Department, GSK CH. Each subject will 
receive a sufficient number of tubes to cover usage during the treatment phase.  
All sundry items will be supplied in their commercial packaging for dispensing by study staff 
as required.  
Care should be taken with the supplied products and their labels so that they are maintained in 
good condition. It is important that all labels remain intact and legible for the duration of the 
study. Subjects should be instructed to not remove or deface any part of the study label.  
All products supplied are for use only in this clinical study and should not be used for any other 
purpose. 
6.1.2 
Preparation and Dispensing  
Study products will be prepared and/or dispensed by qualified unblinded site personnel 
according to the dosage and administration instruction.  
Subjects will be assigned to products in accordance with the randomization schedule generated 
by an approved GSK CH vendor, prior to the start of the study, using validated software. 
Study product will be dispensed by qualified unblinded site personnel per the 
dosage/administration instructions. These staff members will not be involved in any safety, 
efficacy assessments or other aspects of the study that could be influenced by the knowledge of 
product a subject has been assigned to use. An additional member of site staff should ensure the 
dispensing procedures are completed accurately. The investigational products will be dispensed 
in blinded fashion to the subject.  
A record of product dispensing to each subject will be maintained in the dispensing log; 
completion of the dispensing procedure will be recorded in the case report form (CRF). 
6.2 
Administration 
A record of the administration of the study products will be kept using a dispensing log and the 
CRF. 
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Protocol Number: 208175 
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Subjects will be instructed to self-administer their investigational product according to the 
product use instructions provided to the subject. Subjects will receive a brushing 
instruction/diary sheet. This will outline the brushing instructions and will be used to record the 
date and time of each brushing occasion during the treatment period. Subjects will also be asked 
to note any missed brushings, and to use the diary to record any changes in medications, or new 
medications, or to diet. To ensure that subjects understand the dose of dentifrice to be used, 
staff will demonstrate what is meant by a ‘full ribbon’ (i.e. covering the length of the toothbrush 
head) and provide detailed oral hygiene instruction during the supervised toothbrushing in 
agreement with the study schedule and product usage instructions. 
6.2.1 
Medication/Dosing Errors 
Medication/dosing errors may result, in this study, from the administration or consumption of:  
• the wrong product, 
• by the wrong subject,  
• at the wrong time,  
• or at the wrong dosage.  
Such medication/dosing errors occurring to a study subject are to be captured in the CRF.  In 
the event of medication dosing error, the sponsor should be notified immediately and under 
no circumstance should this exceed 24 hours. 
Medication/dosing errors are reportable irrespective of the presence of an associated AE, 
including: 
• Medication/dosing errors involving subject exposure to any of the study products; 
• Potential medication/dosing errors or uses outside of what is foreseen in the protocol 
that do or do not involve the participating subject. 
If a medication/dosing error is accompanied by an AE, as determined by the investigator, the 
medication/dosing error and, any associated adverse event(s) are to be captured in the CRF AE 
form.  
6.2.2 
Overdose 
An overdose is a deliberate or inadvertent administration of a product at an amount higher than 
specified in the protocol. 
Overdose is not likely to occur in this study. 
Limited quantities of the study products 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. 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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6.3 
Investigational/Study Product Storage  
The investigator, or designee, will ensure that all study products are stored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and the product label.   
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should be 
captured from the time of first product receipt throughout the study.  Even for continuous 
monitoring systems, a log or site procedure that ensures active daily evaluation for excursions 
should be available.  The operation of the temperature-monitoring device and storage unit (for 
example, refrigerator), as applicable, should be regularly inspected to ensure it is maintained in 
working order.  
Any excursions from the product-label storage conditions should be reported to appropriate site 
staff upon discovery and communicated to sponsor as soon as possible.  The site should actively 
pursue options for returning the product to the storage conditions as described in the labeling, 
as soon as possible.  Excursions from the storage requirements, including any actions taken, 
must be documented as a protocol deviation and reported to the Sponsor.   
Once an excursion is identified, the affected product (or products) must be quarantined and not 
used until the sponsor provides documentation of permission to use. Use of any of the affected 
product(s) prior to sponsor approval will be considered a protocol deviation.   
Site staff will instruct subjects on the proper storage requirements for all take-home products.  
6.4 
Investigational/Study Product Accountability 
All products supplied are for use only in this clinical study and should not be used for any other 
purpose. 
All study products must be received by a designated person at the study sites, handled and stored 
safely and properly, and kept in a secured location to which only the staff have access. Upon 
receipt, all study products should be stored according to the instructions specified on the product 
labels. Study products are to be dispensed only to subjects enrolled in the study in accordance 
with the protocol, by authorized site staff. 
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of all the product supplies. All study products will be accounted for using the 
investigational/study product accountability form/record. The investigator is responsible for 
study product accountability, reconciliation, and record maintenance.  
Subjects will return used and unused tubes of the washout dentifrice to the investigator site at 
their Baseline visit (Visit 2). Subjects will return used and unused tubes of their assigned study 
dentifrice to the investigator site at their visits to the clinical study site as per the Schedule of 
Activities, with all study products returned at the end of the study (for most subjects this will 
be Visit 6). Study product return will be documented using the investigational/study product 
accountability form/record.  
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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The accountability records must be available for inspection by the study monitor during the 
study. Monitoring of product accountability will be performed by the monitor during site visits 
and at the completion of the study.  
6.4.1 
Destruction of Investigational/Study Product Supplies  
At the end of the study, the Principal Investigator or an appropriate designee, and a 
representative of GSK CH (study monitor) will inventory all used and unused study products 
and sundry items.  The investigational/study product accountability record for returned study 
products will then be completed. All study product (used and unused) for this clinical study 
(including empty containers), will be returned for destruction to GSK CH Clinical Supplies 
Department or designated vendor using the return instructions provided.  
Return and destruction instructions for sundry items are provided in Table 6-2.  
6.5 
Blinding and Allocation/Randomization 
All subjects will be centrally randomized to one of the study arms using an Interactive Response 
Technology (IRT). Before the study is initiated, training, login information and directions for 
the IRT will be provided to the clinical study site. Study products will be dispensed according 
to the instruction received through the IRT at the appropriate study visits. 
Returned study products should not be re-dispensed to any subject. 
This study is described as examiner-blind (the subjects, investigator and clinical examiner(s) 
will be blinded to product received). The study statistician, other employees of the Sponsor 
(including the Clinical Research Scientist (CRS)) and vendors acting on behalf of the sponsor, 
who may influence study outcomes will also be blinded to the product allocation. 
To ensure the examiner remains blinded throughout the study, staff involved in the preparation 
and dispensing of study products will work in a separate area. The examiner is not permitted in 
any area where study product is stored, dispensed, or in use.  
Subjects will be instructed not to remove study products from the opaque bags provided outside 
of the dispensing room, while at the study site. Dispensing staff will not be involved in any 
efficacy/safety assessment procedures during the study.   
Subjects will be stratified at the point of randomization based on their gender and number of 
bleeding sites (Low: < 45/High ≥ 45 bleeding sites) at baseline (see Section 4.1).  
6.6 
Breaking the Blind 
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind.  The method will be an electronic process. 
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
subject’s product assignment is warranted. Subject safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a subject’s 
product assignment unless this could delay emergency treatment of the subject. 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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If a subject’s product assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be recorded in the 
source documentation and case report form, as applicable. 
Any AE associated with breaking the blind must be recorded and reported as specified in this 
protocol. The study site may also be required be required to inform the IRB/EC if the blind is 
broken.  
6.7 
Compliance 
Study products will be administered under the supervision of investigator site personnel.   
A diary will be supplied to promote compliance and to capture details of product use throughout 
the study period. Subjects will also use the diary to note any missed/ additional brushings, the 
reasons for any missed/ additional brushings, any issues with the dentifrice used, oral problems, 
illnesses, AEs, and any new medications/ treatments. Any additional details relevant to efficacy 
or safety should be reviewed by the investigator (or suitably qualified designee) with the 
subjects and transcribed to the CRF as appropriate. Subjects will also attend each study visit 
with all tubes of dentifrice provided (used and unused) for a visual check of product usage, and 
with their completed diary for review by study staff. 
The number of any missed or additional applications or doses will be captured as protocol 
deviations and transcribed from the diary into the CRF. Subjects will be re-instructed in the 
correct usage requirements and diary completion as needed. 
Supervised brushings will be carried out at the study site in agreement with the Schedule of 
Activities, to facilitate subject compliance with dosing and brushing instructions. 
A threshold of compliance with allocated study treatment has been set as 80% of the 
recommended doses.  
6.8 
Concomitant Medication/Treatments 
Any medications, treatments or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) taken during the study, from signing the informed consent, 
must be recorded in the CRF with indication, reason for use, unit dose, daily dose, and start and 
stop dates of administration. All subjects will be questioned about concomitant 
medication/treatments at each site visit. 
Medication/treatments taken within 30 days of signing the informed consent form will be 
documented as a prior medication/treatment.  Medications/treatments taken after first treatment 
dose will be documented as concomitant medication/treatments. 
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Subject Discontinuation/Withdrawal  
A subject may withdraw from the study at any time at his or her own request or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 39 of 77 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures.   
The following circumstances require discontinuation of study product and/or premature subject 
withdrawal: 
• Protocol violation that may impact the subject’s safety 
• Withdrawal of informed consent 
• Subject lost to follow-up  
• Unblinding of the subject  
• Pregnancy 
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal and the associated date must be documented in the relevant 
section(s) of the CRF.  
7.2 
Lost to Follow up 
If a subject fails to return to the site for a required study visit the site must attempt to contact 
the subject and reschedule the missed visit as soon as possible and counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject wishes 
to and/or should continue in the study. 
A subject will be considered lost to follow up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. Before a subject is deemed lost to follow 
up, the investigator or designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods). These contact attempts should be documented. If contact 
is made with the subject, the investigator should inquire about the reason for withdrawal, request 
that the subject return all products that they had been dispensed and if appropriate request that 
the subject return for a final visit and follow-up with the subject regarding any unresolved 
adverse events (AEs) or Incidents. 
Final safety assessments may be carried out when the subject returns to the study site, at the 
investigator’s discretion, which could include the following: an oral examination.  
Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study and lost to follow up.  
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved. 
If the subject withdraws from the study and withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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8 
STUDY PROCEDURES 
This section lists the procedures to be completed at each planned study visit.  The timing of 
each procedure is listed in the Schedule of Activities section. 
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct. 
8.1 
Screening: Visit 1 
Screening procedures will be conducted by the Investigator, or suitably qualified designee. 
8.1.1 
Informed Consent 
The investigator, or designee, must obtain informed consent from each subject participating in 
this study after adequate explanation of the aims, methods, objectives, and potential hazards of 
the study. Two copies of the informed consent form (ICF) will be signed and dated by the 
subject, the subject will retain one copy and the other will be kept at site. 
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 signed and dated consent will be provided by either the investigator or by GSK CH. 
The investigator, or designee, should sign and date each copy of the ICF to confirm that the 
consent process was completed correctly after the subject has signed.   
The time the subject signed the informed consent form will also be captured on the Informed 
Consent Form as this is the point at which all Adverse Events and Incidents will be captured 
from. The date and time of consent will be transcribed to the CRF. 
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. Each subject should 
be provided with a copy of the signed and dated amended consent form. The date of re-consent 
will be recorded on the CRF. 
After signing the ICF, subjects will undergo the screening assessments to confirm that they 
meet all the inclusion criteria and none of the exclusion criteria. If the subject is confirmed 
eligible by the investigator (or designee) to participate in the study the subject is considered 
enrolled in the study. 
e-Consent is a tool that assists in the consent process by using multimedia components delivered 
by an electronic system (e.g. iPad/tablet). The multimedia components consist of video, audio, 
knowledge review, dictionary and electronic signature. 
The site staff can use the system to consent the subject with the benefit of helping the subject 
understand the research they are taking part in and to control the consent process. 
The system will allow for a copy of the consent to be printed and given to the subject and for 
consent documents to be retained by the site in PDF format. 
A GSK CH approved vendor will be used to provide the system and training and help desk will 
be provided as needed. 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 41 of 77 
If the country and/or site does not have approval to use the e-Consent system, or the subject 
does not want to use the e-Consent system, then the conventional paper process will be followed. 
It is possible to use the e-Consent system to educate the subject while using paper to obtain 
signatures. 
8.1.2 
Demographics 
The following demographic information will be recorded in the CRF: year of birth, gender and 
race. 
8.1.3 
Medical History and Prior Medication/Treatment 
Details of relevant medical and surgical history, including allergies or drug sensitivity, will be 
documented in the eCRF. 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to signing the informed 
consent form, will be documented in the eCRF. 
8.1.4 
Screening Procedures 
The following procedures will be completed, and data recorded in the CRF: 
• Informed consent. 
• Demographics, medical history, prior/ current medications (including non-drug 
therapy), & smoking status.  
• Oral soft tissue (OST) examination (Section 9.3.1) 
• Oral hard tissue (OHT) examination (Section 9.3.2) 
• Gross gingival assessment (Section 8.1.6) 
• Female subjects of child-bearing potential only will complete a urine pregnancy test 
(UPT) (Section 9.1.2) 
• Inclusion/exclusion criteria 
• Subject eligibility 
• Dispense washout products/ dentifrice, toothbrush, diary & timer. 
• Oral hygiene instruction & supervised brushing with washout dentifrice.  
• Adverse events & Incidents (Section 10) 
8.1.5 
Oral Examination/Assessment 
Inclusion and exclusion criteria information will be documented in the eCRF. The following 
screening procedures should be carried out by a qualified dental professional: 
• Oral soft tissue (OST) examination (as per Section 9.3.1). 
• Oral hard tissue (OHT) examination (as per Section 9.3.2). 
• Gross 
assessment 
of 
gingival 
health 
(as 
per 
Section 
8.1.6) 
The 
oral 
examinations/assessments should be carried out as described in Section 9. All findings 
will be recorded in the eCRF. 
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8.1.6 
Gross Assessment of Gingival Health 
Visual assessment of gingival health will be performed by the clinical examiner to record the 
presence/absence of generalized mild-moderate plaque-induced gingivitis as per the inclusion 
criteria.  (MGI/BI will not be recorded for this assessment). 
Findings from this examination performed at the Screening Visit will be used to determine 
subject eligibility. 
8.1.7 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information will be documented in the CRF. 
8.1.8 
Subject Eligibility 
The investigator and/or medically qualified designee will review inclusion/exclusion criteria, 
medical history, prior medications to confirm subject eligibility to participate in the clinical trial. 
This will be documented in the CRF. 
To prepare for study participation, subjects will be instructed in the Lifestyle Guidelines and 
any Concomitant Medication/Treatment(s) requirements of the protocol. 
8.1.9 
Supervised Use of Washout Dentifrice 
Eligible subjects will be provided with the washout dentifrice, toothbrush, diary and timer to 
use during the acclimatization period (2-4 weeks). Dentifrice usage instructions will be 
described to the subject and dosing of a full brush head with dentifrice will be demonstrated. 
Staff will supervise the subject carrying out first dosing/brushing with washout dentifrice and 
recording first use in their diary. Completion of all procedures will be documented in the CRF. 
8.2 
Study Period 
8.2.1 
Baseline: Day 0 (Visit 2) 
Subjects will be admitted to the clinical study site 10-28 days after the Screening visit. The 
following procedures/ assessments will take place in the order listed below as much as possible 
and recorded in the CRF: 
• Return washout products/ compliance checks including diary review 
• Review of current/ prior medications and non-drug treatments/ procedures, adverse 
events, incidents and lifestyle restrictions 
• Urine pregnancy testing will be carried out on all female subjects of child bearing 
potential (Section 9.1.2) 
• Full oral soft tissue (OST) examination (Section 9.3.1) 
• Full oral hard tissue (OHT) examination (Section 9.3.2) 
• MGI assessment (& repeatability assessment, where applicable) (Section 9.2.1) 
• BI assessment (Section 9.2.2) 
• Plaque disclosure (Section 9.2.3) 
• TPI assessment (& repeatability assessment, where applicable) (Section 9.2.4) 
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• Inclusion/exclusion criteria 
• Subject eligibility 
• Stratification/randomization 
• Sub- & supra-gingival prophylaxis & flossing (Section 8.4) 
• Plaque disclosure followed by first examiner and second clinician check with 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 
• Concomitant medications/ treatments will be collected as per Section 6.8.  
• Adverse events & Incidents (Section 10) 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond to a 
non-leading question such as “How do you feel?” will be assessed and any AEs recorded in the 
CRF. 
8.2.2 
Day 3, Day 7, Day 14 (Visits 3-5) 
The following procedures/ assessments will take place in the order listed below as much as 
possible and recorded in the CRF: 
• Collect study dentifrice, toothbrush & diary from subject 
• Review of concomitant medications and non-drug treatments/ procedures, adverse 
events, incidents and lifestyle restrictions 
• Compliance checks including diary review 
• Subject continuance 
• Full OST examination (Section 9.3.1) 
• MGI assessment (& repeatability assessment, where applicable) (Section 9.2.1) 
• BI assessment (Section 9.2.2) 
• Plaque disclosure (Section 9.2.3) 
• TPI assessment (& repeatability assessment, where applicable) (Section 9.2.4) 
• Return study dentifrice, toothbrush, study instructions and diary to subject 
• Oral hygiene instruction review / compliance checks including diary completion 
review with subject 
• Supervised subject brushing at site 
• Adverse events & Incidents (Section 10) 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
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Spontaneous reporting of adverse events and those elicited by asking subjects to respond to a 
non-leading question such as “How do you feel?” will be assessed and any AEs recorded in the 
CRF. 
8.2.3 
Day 42 (Visit 6) 
The following procedures/ assessments will take place in the order listed below as much as 
possible and recorded in the CRF: 
• Collect study dentifrice, toothbrush, diary & timer (all study supplies) from subject 
• Review of concomitant medications and non-drug treatments/ procedures, adverse 
events, incidents and lifestyle restrictions 
• Compliance checks including diary review 
• Subject continuance 
• Oral soft tissue (OST) examination (Section 9.3.1) 
• Oral hard tissue (OHT) examination (Section 9.3.2) 
• MGI assessment (& repeatability assessment, where applicable) (Section 9.2.1) 
• BI assessment (Section 9.2.2) 
• Plaque disclosure (Section 9.2.3) 
• TPI assessment (& repeatability assessment, where applicable) (Section 9.2.4) 
• Complete optional second dental prophylaxis (as/ if deemed necessary by examiner) 
(Section 8.5) 
• Adverse events & Incidents (Section 10) 
• Study conclusion (Section 8.6) 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond to a 
non-leading question such as “How do you feel?” will be assessed and any AEs recorded in the 
CRF. 
8.3 
Diary Review 
The diary should be reviewed at every visit by the investigator, or suitably qualified designee, 
and the subject. Any subject comment captured in the diary which is considered an adverse 
event or Incident will be assessed and reported as per the defined procedure in this protocol. 
Adverse event reporting procedures are summarized in Adverse Event and Serious Adverse 
Events. Incident reporting procedures are summarized in Definition of and Procedure for 
Reporting Medical Device Incidents (Section 10.9). 
Any additional comments relating to medications/treatments provided in the diary will be 
reviewed by the investigator or medically qualified designee with the subject and entered into 
the CRF as appropriate.  
Additional and missed product applications will be considered deviations from the protocol and 
will be recorded on the Deviations Log. 
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8.4 
Dental Prophylaxis 
A suitably qualified member of clinical staff (e.g. a dentist or hygienist) will provide 
professional dental prophylaxis for each randomized subject (using conventional prophylaxis 
paste and periodontal instruments as required), followed by flossing, to remove sub- and supra-
gingival calculus, stain, plaque and debris from the teeth. A second clinician will confirm all 
sub- and supra-gingival calculus, visible stain, plaque and debris has been removed (visually, 
and by tactile examination using a dental explorer). If necessary, additional dental cleaning will 
be carried out to achieve this. Prophylaxis may be carried out by different clinicians to facilitate 
subject flow.  
Following prophylaxis, it should be confirmed that the subject whole mouth post-prophylaxis 
TPI = 0. Completion of this procedure should be recorded in the eCRF. 
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 as detailed 
in Section 8.5.  
8.5 
End of Study Optional Prophylaxis 
Subjects who, in the opinion of the clinical examiner, would benefit from dental prophylaxis 
following their participation in the study will be offered full mouth dental prophylaxis (using 
conventional prophylaxis paste and periodontal instruments as required) on completion of all 
clinical assessments. Prophylaxis may be carried out by different, appropriately qualified 
clinicians to facilitate subject flow. 
8.6 
Study Conclusion 
The Study Conclusion page of the CRF will be completed for all subjects whether they 
completed all study procedures or if they were discontinued from the study early.  If the subject 
discontinued early, at any point during the study, the primary reason for withdrawal should be 
recorded on the Study Conclusion page. 
If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the GSK CH medical monitor (or designated representative) should be notified and, the 
subject may be asked to remain at the clinical site or be asked to return for a follow-up visit to 
ensure any issue is resolved or deemed not clinically significant.  
8.7 
Follow-up Visit/ Phone Call 
The study site may contact a subject to follow up an AE or Incident post-study 
completion/withdrawal and, in some circumstances, request they return to the site for additional 
follow-up visits (final safety assessments). If needed, additional examinations may be carried 
out at such visits. 
9 
STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required tests and procedures are completed 
as described.  However, it is anticipated that from time to time there may be circumstances, 
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outside the control of the investigator that may make it unfeasible to complete an assessment.  
In these cases, the investigator must take all steps necessary to ensure the safety and well-being 
of the subject.  When a protocol-required assessment cannot be performed, the investigator (or 
designee) will document the reason for the missed assessment as a protocol deviation and any 
corrective and preventative actions that he or she has taken to ensure that required processes are 
adhered to as soon as possible.  The Sponsor must be informed of any missed assessments in a 
timely manner. 
9.1 
Screening Assessments 
Screening assessments will be performed by appropriately trained staff/clinical examiners at 
the times, and in the order, defined in the Study Procedures section of this protocol. A single 
examiner will be responsible for the conduct of the clinical measures of gingivitis/ plaque 
accumulation for the duration of the study.  
Eligible tooth assessments will be accomplished by oral examination and will evaluate dentition 
exclusions along with a gross gingival assessment in relation to the general dentition inclusion/ 
exclusion criteria. Assessments will be carried out by the investigator, or qualified designee, 
against the inclusion/ exclusion criteria. Ineligible subjects will not be re-screened.  
9.1.1 
Gross Assessment of Gingival Health 
Visual assessment of gingival health will be performed to record the presence/absence of 
generalized mild-moderate plaque-induced gingivitis as per the inclusion criteria.  (MGI/BI will 
not be recorded for this assessment). 
Findings from this examination performed at the Screening Visit will be used to determine 
subject eligibility. 
9.1.2 
Urine Pregnancy Testing 
For female subjects of childbearing potential, a urine pregnancy test, will be performed at 
Screening (Visit 1) and Baseline (Visit 2).  Results will be obtained prior to dosing during each 
visit.  
The investigator and site personnel will remind subjects at each visit to inform site personnel if 
their menstrual cycle has changed or if they have any other reason to suspect they may be 
pregnant (e.g. had unprotected intercourse since the last visit). 
A negative pregnancy result is required before the subject may receive the investigational 
product.  Pregnancy tests will also be done whenever one menstrual cycle is missed during the 
active study period (or when potential pregnancy is otherwise suspected). Pregnancy tests may 
also be repeated as per request of IRBs/ECs or if required by local regulations. 
In the case of a positive confirmed pregnancy, the subject will be withdrawn from 
administration of investigational product and from the study. 
9.2 
Efficacy Assessments 
The following efficacy assessments will be performed by appropriately trained staff/clinical 
examiners, at the times and in the order defined in the Study Procedures section of this protocol 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 4 7  of 7 7  
T he sa me e x a mi ner will be use d t hr o u g h o ut t he st u d y f or eac h cli nical i n de x t o eli mi nate t he 
p ossi bilit y of i nter -e x a mi ner vari a bilit y.  
9. 2. 1  
M o difi e d Gi n gi v al I n d e x ( M GI) A s s e s s m e nt 
) 
T he M GI assess me nt is a n o n -i n vasi ve e val u ati o n w hich f oc uses o n t he vis ual s y m pt o ms of 
gi n gi vitis (f or e x a m ple, re d ness, te xt ure, e de ma).  T he M GI will be assess e d o n t he faci al a n d 
li n g ual s urfaces of eac h sc ora ble t o ot h (sec o n d per ma ne nt m olar t o sec o n d per ma ne nt m olar i n 
eac h arc h) b y a n a p pr o priatel y q u alifie d e x a mi ner.  T w o sc ores 
will be rec or de d 
b uc call y/la biall y ( pa pilla a n d mar gi n) a n d t w o sc ores li n g uall y/ palat all y ( pa pilla a n d mar gi n).  
T he sc ori n g of t he M GI will be perf or m e d u n der de ntal office c o n diti o ns usi n g a sta n dar d de ntal 
li g ht f or ill u mi nati n g t he oral ca vit y. 
T he M GI sc ori n g s yste m will be as f oll o ws:   
T a bl e 9 -1  
M o difi e d Gi n gi v al I n d e x  s c ori n g s y st e m  
S c or e  
D e s cri pti o n  
0  
A b s e n c e of i nfl a m m ati o n  
1  
Mil d i nfl a m m ati o n; sli g ht c h a n g e i n c ol o ur, littl e c h a n g e i n c ol o ur; littl e c h a n g e i n t e xt ur e 
of a n y p orti o n of t h e m ar gi n al or p a pill ar y gi n gi v al u nit  
2  
Mil d i nfl a m m ati o n; crit eri a a s a b o v e b ut i n v ol vi n g t h e e ntir e m ar gi n al or p a pill ar y gi n gi v al 
u nit  
3  
M o d er at e i nfl a m m ati o n; gl a zi n g, r e d n e s s, e d e m a, a n d/ or h y p ertr o p h y of t h e m ar gi n al or 
p a pill ar y gi n gi v al u nit  
4  
S e v er e i nfl a m m ati o n; m ar k e d r e d n e s s, e d e m a a n d/ or h y p ertr o p h y of t h e m ar gi n al or 
p a pill ar y gi n gi v al u nit, s p o nt a n e o u s bl e e di n g, c o n g e sti o n, o r ul c er ati o n.  
T he M GI will be assesse d b y t he s a me e x a mi ner o n all e val ua ble t eet h fr o m Baseli ne o n war ds 
as i n dicate d i n t he Sc he d ule of Acti vities.   
9. 2. 2  
Bl e e di n g I n d e x ( BI) A s s e s s m e nt  (
) 
T he BI assesses t he n u m ber of blee di n g p oi nts elicite d o n pr o bi n g as a m eas ure of gi n gi v al 
c o n diti o n.  T he gi n gi v ae will be air drie d a n d t he n t he e x a mi ner will use a n O uli x c ol or c o de d 
peri o d o nta l P C PII 5 B H u-F rei d y or bl u nt-e n de d C PI pr o be t o assess blee di n g.  T he pr o be will 
be ge ntl y i ns erte d i nt o t h e gi n gi val cre vi ce t o a d e pt h of a p pr o xi matel y 1 milli meter ( m m) a n d 
t he n r u n ar o u n d t he t o ot h (at a n gl e of ~ 6 0º t o t he l o n g a xis of t he t o ot h), gentl y stretc hi n g t he 
e pit heli u m w hile s wee pi n g fr o m i nter pr o xi mal t o i nter pr o xi mal al o n g t h e s ulc ular e pit heli u m.  
Mi ni m u m f orce s h o ul d b e use d t o a v oi d da ma ge t o t he gi n gi val tiss ue.  T h e BI will be assesse d 
o n t he facial a n d li n g ual gi n gi val s urfaces of e ac h sc ora bl e t o ot h ( 7 -7 i n eac h arc h).  T hree 
sc ores (acc or di n g t o t he s cale b el o w) s h o ul d b e rec or de d b uc call y/la biall y ( distal, b o d y, mesi al 
sites) a n d t hree sc ores li n g uall y/ palatall y.  All sc ora ble teet h i n o ne q ua dra nt s h o ul d be pr o be d 
first (a p pr o xi matel y 3 0 s ec o n ds) bef ore rec or di n g t he n u m ber of gi n gi val u nits w hic h blee d.  
T he BI s c ori n g s yste m will be as f oll o ws:  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 4 8  of 7 7  
T a bl e 9 -2  
Bl e e di n g I n d e x s c ori n g s y st e m  
S c or e  
D e s cri pti o n  
0  
N o bl e e di n g aft er 3 0 s e c o n d s  
1  
Bl e e di n g o b s er v e d wit hi n 3 0 s e c o n d s of pr o bi n g  
2  
Bl e e di n g o b s er v e d i m m e di at el y o n pr o bi n g  
T he BI will be ass esse d b y t he s a me e x a mi ner o n all e val ua ble teet h fr o m Baseli ne o n war ds as 
i n dicate d i n t he Sc he d ule of Acti vities.  
Re pe at a bilit y e xercise will n ot be perf or me d f or BI.  
9. 2. 3  
Pl a q u e Di s cl o s ur e  
De ntal pla q ue is c ol orless a n d s o is us uall y dis cl ose d (‘stai ne d’) pri or t o assess me nt. T he 
discl osi n g s ol uti o n will b e use d acc or di n g t o t he ma n ufact ur er’s i nstr ucti o ns.  
•  At t he re q uest of t he s u bject, t he cli nicia n ma y a p pl y a t hi n la yer of petr ol e u m jell y t o 
t he s u bject’s li ps, as a barrier t o hel p mi ni mize stai ni n g b y t he discl osi n g s ol uti o n. Care 
s h o ul d be ta ke n t o ens ur e n o petr ole u m jell y c o mes i nt o c o ntact wit h t he la bial s urfaces 
of t he a nteri or t eet h as t his c o ul d i m pact cli nical assess me nts i n t his re gi o n.  
•  T he s u bject will ri nse t heir m o ut h wit h 1 0 m L ta p water f or 1 0 sec o n ds t o re m o ve a n y 
f o o d de bris a n d e x pectorate.  
•  T he cli nicia n will t he n a p pl y t he p la q ue discl osi n g s ol uti o n as per t he la bel i nstr ucti o ns. 
Care will be ta ke n n ot t o disl o d ge t he pla q ue d uri n g t his pr ocess. T he s u bject will t he n 
ri nse wit h 1 0 m L ta p wat er f or 1 0 s ec o n ds a n d e x pect orate t o re m o ve e x cess s ol uti o n. 
Pla q ue ma y b e re discl os e d bet w ee n t he T PI a n d re p eat assess me nts at t he discreti o n of t h e 
cli nical e x a mi ner.  
9. 2. 4  
Pl a q u e I n d e x ( T PI) A s s e s s m e nt (
) 
T he T ures k y M o dificati o n of t he Q ui gle y Hei n Pla q ue I n de x (
) will be use d 
t o assess pla q ue o n all gra da ble t eet h meeti n g t he i ncl usi o n/ e x cl usi o n criteria, a n d will be 
perf or me d b y a n a p pr o priatel y q u alifie d e x a mi ner. O nl y n at ural teet h ca n be assesse d.  T his 
mea ns n o cr o w ns, bri d ges, a n d teet h wit h filli n gs (s urface t hat has 5 0 % of t he s urface gra da bl e 
or n o m ore t ha n 5 0 % of t he s urface fille d) w hic h, i n t he  e x a mi ner’s j u d g m e nt, w o ul d pre ve nt 
a n acc urate gra di n g s h o ul d be assesse d.  T hir d m olars s h o ul d n ot t o be assesse d.  
T he pla q ue will first be discl ose d usi n g a pl a q ue discl osi n g d ye s ol uti o n, i n a gree m e nt wit h t he 
ma n ufact ur er’s i nstr ucti o ns.  T he T PI will  be assesse d o n t he facial a n d li n g ual s urfaces of eac h 
sc ora ble t o ot h. ( 7-7 i n eac h arc h). T hree s c ores s h o ul d be rec or de d b ucall y/ la biall y ( distal, 
b o d y, mesial sites) a n d t hree sc ores li n g uall y/ p alatall y ( distal, b o d y, mesial sites).  
Discl ose d pla q ue  will be sc ore d as f oll o ws:  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI
C CI

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Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 49 of 77 
Table 9-3 
Turesky Plaque Index Scoring System 
Score 
Description  
0 
No plaque 
1 
Separate flecks of plaque at the cervical margin  
2 
Thin continuous band of plaque (up to 1 mm) at the cervical margin  
3 
Band of plaque wider than 1 mm but covering < 1/3 of the tooth surface 
4 
Plaque covering ≥ 1/3 but < 2/3 of the tooth surface 
5 
Plaque covering ≥ 2/3 of the tooth surface 
The TPI will be assessed by the same examiner on all evaluable teeth from Baseline onwards 
as indicated in the Schedule of Activities.  
9.2.1 
Repeatability Assessments 
The clinical examiner selected for this study will have demonstrated their ability to replicate 
their own scores (intra-examiner repeatability) on a tooth site-by-tooth site basis in previous 
studies and/or calibration exercises. Repeat MGI and TPI assessments will be performed by the 
clinical examiner at Visits 2 - 6. At least 2 repeat assessments should be performed for each 
index on each clinical assessment day (≥1 in the morning; ≥1 in the afternoon). ‘Repeat’ 
subjects will be selected at random from those in attendance. Different subjects can be used for 
repeat MGI and TPI assessments.  
There should be a delay of at least 10 minutes between original and repeat assessments for a 
given subject and ideally separated by another subject. No other procedure on the subject should 
be carried out between the first and the repeat assessment. Where possible, the clinical examiner 
should assess a different subject in the intervening period. 
Scores from the first assessment must not be visible to the examiner/scribe when the repeat 
assessment is carried out. 
9.3 
Safety and Other Assessments 
The following safety assessments will be performed by appropriately trained staff/clinical 
examiners, at the times and in the order defined in the Study Procedures section of this protocol.   
9.3.1 
Oral Soft Tissue Examination (OST) 
Where possible, this procedure should be conducted by a single dental examiner or clinically 
qualified designee. The OST 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, tonsillar area, pharyngeal area, tongue, sublingual area, 
submandibular area and salivary glands. 
The results of the examination will be recorded in the CRF as either normal or abnormal, with 
details of any abnormalities.  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 a pre-existing condition observed by the clinical 
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Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 50 of 77 
examiner or reported by the subject from the OST examination carried out at Screening will be 
recorded as an AE.  
During the oral examination, if any abnormalities on the oral soft tissues are detected, the 
subject will be advised to seek further medical/ dental advice from their dentist or general 
medical practitioner as deemed appropriate in the opinion of the clinical examiner.  
9.3.2 
Oral Hard Tissue (OHT) Assessment 
Where possible, this procedure should be conducted by a single dental examiner or clinically 
qualified designee for all subjects. Subjects with evidence of gross intra-oral neglect or the need 
for extensive dental therapy will be excluded.  
The OHT examination will assess grossly carious lesions or signs of erosive wear, enamel 
irregularities, tooth fracture, gross decay, decalcification, faulty restorations and implants. The 
examination will be performed by direct observation. 
During the oral examination, if any abnormalities on the oral hard tissues are detected, the 
subject will be advised to seek further medical/ dental advice from their dentist or general 
medical practitioner. 
Observations will be listed as “Absent” or “Present” and conditions noted as present will be 
described. Examination findings will be described and documented in the CRF. Any 
abnormalities or worsening of a pre-existing condition observed by the clinical examiner or 
reported by the subject from the OHT examination carried out at Screening will be recorded as 
an AE.  
10 
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS 
10.1 
Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of a study product including any washout or lead-in product (or medical device), 
whether or not considered related to the study product, including any washout or lead-in product 
(or medical device). 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study product including any washout or lead-in product (or medical device). 
Events Meeting the AE Definition:   
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g. ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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• New conditions detected or diagnosed after study product administration even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
product or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy will be reported as AE if they fulfill the definition of an AE.  
Events NOT meeting the AE definition:  
• 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 being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition.  
• Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis). 
• Situations where an untoward medical 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.  
10.2 
Definition of a Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse 
outcome is serious. If an event is not an AE per definition above, then it cannot be an SAE even 
if serious conditions are met (e.g. hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A serious adverse event is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening  
▪ The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe; 
• Requires inpatient hospitalization or prolongation of existing hospitalization  
▪ 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 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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physician’s office or outpatient 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. 
• Results in persistent or significant disability/incapacity 
▪ The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
▪ This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption 
• Results in congenital anomaly/birth defect 
• Other situations: 
▪ Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
▪ Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Note: Classification of an AE as ‘serious’ is based on the outcome of the event and is a factor 
in determining reporting requirements. 
10.3 
Reporting of Adverse Events 
10.3.1 
Reporting Period  
All AEs, and therefore all SAEs will be collected immediately after a subject consents to 
participate in the study by the completion (signature) of the ICF and until 5 days following last 
administration of the study product (or last procedure).  
Medical occurrences that began before obtaining informed consent will be recorded in the 
Medical History/Current Medical Conditions section of the CRF not the AE section. 
Details recorded by the subject on a diary or similar document that meet the definition of an AE 
must also be discussed with the subjects and transcribed in the AE section of the CRF.  
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 53 of 77 
10.4 
Reporting Procedures 
The investigator and any designees are responsible for detecting, documenting and reporting 
events that meet the definition of an AE and remain responsible for following up on AEs that 
are serious, considered related to the study product(s), participation in the study, or a study 
procedure, or that caused the subject to discontinue the study product or study.  
The investigator (or medically qualified designee) is to report all directly observed AEs and all 
AEs spontaneously reported by the study subject. In addition, each study subject will be 
questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for a SAE.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
When an AE occurs, it is the responsibility of the investigator (or medically qualified designee) 
to review all documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
The investigator or site staff will then record all relevant information regarding an AE in the 
CRF and all details relating to an SAE in the paper SAE Form provided. 
It is not acceptable for the investigator (or medically qualified designee) to send photocopies 
of the subject’s medical records to GSK CH in lieu of completion of the AE CRF page/SAE 
form. 
There may be instances when copies of medical records for certain cases are requested by GSK 
CH.  In this instance, all subject identifiers, except for the subject number, will be redacted on 
the copies of the medical records prior to submission to GSK CH. 
The investigator (or medically qualified designee) will attempt to establish a diagnosis of the 
event based on signs, symptoms, and/or other clinical information.  The diagnosis will be the 
documented as the AE/SAE where known and not the individual signs/symptoms. (e.g. upper 
respiratory tract infection, seasonal allergy, etc. instead of runny nose). 
AEs elicited by the investigator (or medically qualified designee) in a standard manner at the 
study visits should also be recorded in the AE section of the CRF and/or using the SAE form 
(subject to the classification of the AE). Care will be taken not to introduce bias when 
questioning a subject about any changes in their health. Open-ended and non-leading verbal 
questioning should be used. 
10.4.1 
Reporting of an Adverse Event 
All AEs will be reported on the AE page of the CRF by the investigator or site staff.  It should 
be noted that the form for collection of SAE information is not the same as the AE CRF.  Where 
the same data are collected, the AE CRF page and the SAE form must be completed in a 
consistent manner.  For example, the same AE term should be used on both.  AEs should be 
reported using concise medical terminology on the CRF as well as on the form for collection of 
SAE information. 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 5 4  of 7 7  
1 0. 4. 2  
R e p orti n g of a S eri o u s A d v er s e E v e nt  
I n a d diti o n t o rec or di n g t he details of eac h A E o n t he A E C R F pa ge, a n S A E f or m s h o ul d be 
c o m plete d, as  f ull y as p ossi ble. Har d c o pies of t he ‘ pa p er’ S A E f or m will be pr o vi de d i n t h e 
i n vesti gat or st u d y master file. Ori gi nal S A E f or ms will be retai ne d i n t he i n vesti gat or st u d y 
master file.  
It is esse ntial t o e nt er t he f oll o wi n g i nf or mati o n:  
•  Pr ot oc ol a n d s u bject i de ntifiers 
•  S u bject de m o gra p h y  
•  Descri pti o n of e v e nts, wit h dia g n osis if a vaila bl e  
•  I n v esti gat or o pi ni o n of relati o ns hi p t o st u d y pr o d uct ( or st u d y pr oce d ure, if a p pr o priate) 
•  Criteri o n f or seri o us ness.  
T he f oll o wi n g are desir a ble a n d are of partic ul a r rele va nce f or i n vesti gat or a n d G S K C H 
assess me nt of t he S A E re p ort:  
•  Date of o nset of A E  
•  Date A E st o p pe d, if rele v a nt  
•  St u d y pr o d uct start dat e  
•  St u d y pr o d uct e n d d ate if rele va nt  
•  Acti o n ta ke n i n relati o n t o t he st u d y pr o d u ct  
•  O utc o me if k n o w n  
T he S A E f or m,  c o m plete d as f ull y as p ossi ble, m ust be sca n n e d a n d e -maile d t o t he G S K C H 
Cli nical O perati o ns Safet y Re p orti n g e mail b o x wit h t he st u d y n u m ber a n d s u bject n u m ber i n 
t he s u bject li ne of t he e m ail i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 
h o urs  after st u d y site pers o n nel lear n of t he e ve nt. T he i n vesti gat or will s u b mit a n y u p dat e d 
S A E data t o t he s p o ns or, i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 
h o urs of it bei n g a vaila bl e. T he G S K C H St u d y M a na ger s h o ul d als o be n otifie d of t h e sit uati o n 
b y tele p h o n e or e m ail.  
E m ail Seri o us A d verse E ve nts t o:  
 
T he G S K C H St u d y Ma n a ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
t he Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal Cli nical Safet y a n d P har mac o vi gila nce 
mail b o x 
. 
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q ueste d b y t h e 
G S K C H st u d y ma na ger.  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
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10.5 
Evaluating Adverse Events  
10.5.1 
Assessment of Intensity 
The investigator or medically qualified designee will make an assessment of intensity for each 
AE 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.  
NOTE: An AE that is assessed as severe should not be confused with an SAE. Severe is a 
category utilized for rating the intensity of an event; and both non-serious AEs and SAEs can 
be assessed as severe. For example, a headache may be severe (interferes significantly with the 
subject's usual function) but would not be classified as serious unless it met one of the criteria 
for SAEs, listed above. An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
10.5.2 
Assessment of Causality 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. For each AE (serious and non-serious), the investigator (or medically qualified 
designee) must provide an assessment of causality on the AE CRF page and the SAE form 
(subject to the classification of the AE). The investigator will also document in the medical 
notes that he/she has reviewed the AE and assessed causality, where applicable.  
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be provided. 
The investigator will use clinical judgment to determine the relationship and will also consult 
the Investigator Brochure (IB), Safety Statement and/or Product Information, for marketed 
products, in the determination of his/her assessment.  Alternative causes, such as underlying 
disease(s), concomitant therapy, other risk factors, and the temporal relationship of the event to 
the study product will be considered and investigated. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the SAE reporting requirements if applicable. 
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 CH. The investigator may change his/her opinion of 
208175 | Protocol 208175 Clinical Protocol 07 Feb 2021 | TMF-48068 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 5 6  of 7 7  
ca usalit y i n li g ht of f o ll o w-u p i nf or mati o n a n d se n d a n S A E f oll o w -u p re p ort wit h t he u p date d 
ca usalit y assess me nt.  
1 0. 6  
F oll o w -u p of A d v er s e E v e nt s  
After t he i nitial re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w u p wit h eac h s u bject 
a n d pr o vi de f urt her i nf or mati o n o n t he s u bject’s c o n diti o n.  
All A Es (seri o us a n d n o n -seri o us) will be f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n sta bilizes, 
u ntil t he e ve nt is ot her wise e x plai ne d, or u ntil t he s u bject is l ost t o f oll o w -u p.   
T he i n vesti gat or is o bli gate d t o perf or m or ar ra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as ma y be i n dicate d or as re q ueste d b y G S K C H t o el uci date 
as f ull y as p ossi ble t he nat ure a n d/ or ca usalit y of t he A E. T his ma y i ncl u de a d diti o nal la b orat or y 
tests or i n vesti gati o ns, hist o pat h ol o gical e x a mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals.  
Ne w or u p d ate d i nf or m ati o n will be rec or de d o n t he A E C R F pa ge a n d o n t he S A E f or m (s u bject 
t o t he classificati o n of t h e A E). 
T he i n vesti gat or will s u b mit a n y u p date d S A E d a ta t o G S K C H wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n. 
I n v esti gat ors are n ot o bli ge d t o acti vel y see k A Es i n f or mer s u bjects.  H o we v er, if t he 
i n vesti gat or le ar ns of a S A E, i ncl u di n g d eat h, at a n y ti me after a s u bject h as bee n dis c har ge d 
fr o m t he st u dy, a n d c o nsi ders t he e ve nt reas o n a bl y rel ate d t o t he st u d y pr o d uct or st u d y 
partici pati o n, t he i n vesti gat or will pr o m ptl y n otif y G S K C H b y e maili n g t he i nf or mati o n t o t he 
G S K C H Cli nical O p erati o ns Safet y Re p orti n g e mail b o x 
). 
T he G S K C H St u d y Ma na ger or desi g nee will be res p o nsi ble f or f or war di n g t he i nf or mati o n t o 
t he Case Ma n a ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila n ce gr o u p mail b o x at 
G S K 
). 
T he i n vesti gat or will s u b mit a n y u p dat e d S A E dat a t o G S K C H wit hi n t he desi g nat e d re p orti n g 
ti me fra mes. 
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt  
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her  ca us es, acc or di n g 
t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F pa ge.  
W he n a s u bject wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da n ce wit h 
t he re p orti n g re q uire me nts defi ne d. 
1 0. 7. 1  
S p o n s or’ s R e p orti n g R e q ui r e m e nt s t o R e g ul at or y A ut h oriti e s a n d 
Et hi c s C o m mitt e e s  
G S K C H has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ul at or y a ut h orit y a n d 
ot her re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n.  Pr o m pt 
n otific ati o n of S A Es b y t he i n vesti gat or t o G S K C H is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
P P D
P P D

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 5 7  of 7 7  
G S K C H will c o m pl y wit h c o u ntr y s p ecific re g ulat or y re q uire m e nts relati n g t o safet y re p orti n g 
t o t he re gulat or y a ut h orit y, I R B/ E C a n d i n vesti gat ors.  
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y a n d f or war de d t o 
i n vesti gat ors as n ecessar y. 
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n e. g. s u m mar y or listi n g of S A E fr o m t he s p o ns or will re vie w a n d t he n file it 
al o n g wit h t he I n vesti gat or’s Br oc h ure i n t he i n vesti gat or st u d y m aster file, a n d will n otif y t h e 
I R B/I E C, if a p pr o priate acc or di n g t o l ocal r e q uire me nts. 
1 0. 8  
Pr e g n a n c y  
1 0. 8. 1  
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n  
Pre g n a nc y i nf or mati o n will be c ollecte d o n all pre g na nci es re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he si g ni n g of i nf or me d c o ns e nt u ntil 5  da ys aft er last 
a d mi nistrati o n of st u d y pr o d uct.  
1 0. 8. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s  
T he i n vesti gat or will rec or d pre g n a nc y i nf or m ati o n o n t he a p pr o priate f or m sca n a n d e -mail it 
t o t he 
G S K 
C H Cli nical 
O perati o ns 
Safet y 
R e p orti n g e mail b o x (
 wit hi n 2 4 h o urs of lear ni n g of t he s u bject bec o mi n g pre g na nt. T he G S K C H 
St u d y Ma na ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he pre g n a nc y f or m t o t he Cas e 
Ma na ge me nt 
Gr o u p, 
Gl o bal 
Cli nical 
Safet y 
a n d 
P har mac o vi gila nce 
mail b o x 
). Ori gi nal pre g na n c y i nf or mati o n f or ms 
will be retai ne d i n t he 
i n vesti gat or st u d y master file.  
T he s u bject will be f oll o we d t o deter mi ne t he o ut c o me of t he pre g n a nc y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa nt / ne o n ate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t h e 
m ot her d uri n g t he pre g n a nc y) will be f or war de d b y t he i n vesti gat or t o t he G S K C H Cli nical 
O perati o ns Safet y R e p orti n g e mail b o x a n d t he G S K C H St u d y Ma n a ger or desi g nee will 
f or war d t his i nf or mati o n t o t he Case 
Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d 
P har mac o vi gila nce gr o u p mail b o x at G S K (
). Ge nerall y, f oll o w-u p will 
be n o l o n ger t h a n 6 t o 8 wee ks f oll o wi n g t he esti mate d deli ver y d ate. A n y ter mi nati o n of t h e 
pre g na nc y will be re p ort e d.  
W hile pre g na n c y itself is n ot c o nsi dere d t o be a n A E, a b n or mal pre g na nc y o utc o mes (e. g. 
s p o nta ne o us a b orti o n, fet al deat h, still birt h, c o n ge nital a n o malies, ect o pic pre g na nc y) are, a n d 
s h o ul d be rec or de d as a n S A E. 
A n y fe m ale s u bject w h o bec o mes pre g na nt w hile partici pati n g will  disc o nti n ue st u d y treat me nt 
a n d/ or be wit h dra w n fr o m t he st u d y.  
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10.9 
Definition of and Procedure for Reporting Medical Device 
Incidents 
Medical devices are being provided by GSK CH for use in this study; the medical devices in 
this study are the toothbrushes and urine pregnancy test kits.  
10.9.1 
 Definition of an Incident 
A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device as well as any inadequacy in the labeling or the instructions for use 
which, directly or indirectly, might lead to or might have led to the death of a subject/user/other 
person or to a serious deterioration in his/her state of health. 
Not all incidents lead to death or serious deterioration in health. The nonoccurrence of such a 
result might have been due to other fortunate circumstances or to the intervention of health care 
personnel. 
It is sufficient that: 
An incident associated with a device happened and 
• The incident was such that, if it occurred again, might lead to death or a serious 
deterioration in health. 
• A serious deterioration in state of health can include any of the following: 
• Life-threatening illness 
• Permanent impairment of body function or permanent damage to body structure 
• Condition necessitating medical or surgical intervention to prevent one of the 
above  
• Fetal distress, fetal death, or any congenital abnormality or birth defects 
Examples of incidents: 
• A subject, user, caregiver, or healthcare professional is injured as a result of a medical 
device failure or its misuse. 
• A subject’s study treatment is interrupted or compromised by a medical device failure. 
• A misdiagnosis due to medical device failure leads to inappropriate treatment. 
• A subject’s health deteriorates due to medical device failure. 
10.9.2 
Reporting of Incidents and Malfunctions 
All incidents must be reported to GSK CH immediately and under no circumstance should 
this exceed 24 hours 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, if 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 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 5 9  of 7 7  
(seri o us a n d n o n-seri o us), t he a p pr o priate A E C R F pa ge a n d S A E f or m will be c o m plete d a n d 
re p orte d as per t he A E a n d S A E re p orti n g secti o ns. 
T he I nci de nt Re p ort F or m will be c o m plete d as t h or o u g hl y as p ossi ble a n d si g ne d b y t he 
i n vesti gat or bef ore tra ns mittal t o G S K C H.  It is ver y i m p orta nt t hat t he i n vesti gat or d escri bes 
a n y c orrecti ve or re me di al acti o ns ta ke n t o pr e ve nt rec urre nce of t he i nci de nt.  
T he c o m plete d I nci d e nt Re p ort F or m s h o ul d be s ca n ne d a n d e maile d t o t h e G S K C H Cli nical 
O perati o ns Safet y Re p orti n g e mail b o x wit h t he st u d y n u m ber a n d s u bject n u m ber i n t he s u bject 
li ne of t he e mail i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs after 
st u d y site pers o n n el lear n of t he e ve nt. If t here is a n S A E, t he c o m plete d S A E f or m s h o ul d be 
se nt t o get h er wit h t his re p ort f or m.  H o wever, if a c o p y of t he S A E re p ort is se nt wit h t his f or m, 
t his d oes n ot re place t he pr oce d ure t o re p ort a n S A E.  T h e ori gi nal I nci de nt Re p ort F or m will 
be retai ne d i n t he i n v esti gat or st u d y master file.  
T he G S K C H St u d y Ma n a ger s h o ul d be n otifie d of t he si t uati o n b y tele p h o ne or e mail. 
E m ail t he I nci de nt Re p ort F or ms t o:  
 
T he G S K C H St u d y Ma n a ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he I n ci de nt Re p ort 
F or m t o t he Case  Ma na ge m e nt Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila nce gr o u p 
mail b o x 
, res p o nsi ble f or t he st u d y a n d ot her G S K C H pers o n nel as 
a p pr o priate.  
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q ueste d b y t h e 
G S K C H st u d y ma na ger.  
T he i n vesti gat or will f oll o w t he f oll o wi n g directi o ns re gar di n g t h e re p orti n g of a de vi ce fail ure 
( malf u ncti o n): 
•  N otif y G S K C H i m me di atel y ( b y f oll o wi n g t he pr ocess descri be d a b o v e).  
•  Sc h e d ule t he s u bject t o ret ur n t o t he site pr o m ptl y t o ret ur n t he faile d d e vice.  
•  Rec or d a n y i nci d e nts o n t he C R F a n d I n ci de nt Re p ort F or m f oll o wi n g i nstr ucti o ns gi ve n 
i n t he secti o n a b o ve. 
•  Ret ur n t he faile d d e vice t o t he s p o ns or as s o o n as p ossi ble, i ncl u di n g  d oc u me ntati o n of 
t he details of t he fail ure. 
1 0. 9. 3  
F oll o w -u p of M e di c al D e vi c e I n ci d e nt s  
Me dical d e vice i nci de nts i n v ol vi n g a n A E will be f oll o we d a n d re p orte d i n t he sa me ma n ner as 
ot her A Es. T his a p plies t o all s u bjects, i ncl u di n g t h ose w h o disc o nti n ue st u d y pr o d uct or are 
wit h dra w n fr o m t he st u d y.  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat f oll o w -u p i ncl u des a n y s u p ple me nt al 
i n vesti gati o ns as i n dicate d t o el uci date t he nat ur e a n d/ or ca us alit y of t he i n ci de nt. 
Ne w or u p date d i nf or mati o n will be rec or de d  o n t h e ori gi nall y c o m plete d I n ci de nt Re p ort f or m 
wit h all c ha n ges si g ne d a n d date d b y t he i n vesti gat or.  
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
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10.9.4 
Regulatory and Ethics Reporting Requirements for Incidents 
To fulfill regulatory reporting obligations worldwide, the investigator is responsible for the 
detection and documentation of events meeting the definitions of incident or malfunction that 
occur during all periods of the study in which the medical device is used.  
The investigator will promptly report all incidents occurring with any medical device provided 
for use in the study in order for the sponsor to fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies. 
The investigator, or responsible person according to local requirements (e.g. the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of incidents to the IRB/IEC. 
11 
DATA MANAGEMENT 
As used in this protocol, the term CRF is understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method.  
For this study, subject data will be entered into an electronic CRF (eCRF), using a validated 
system. Data relating to SAEs, pregnancy and incidents will also be collected on paper forms. 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
The source documents (e.g. hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, evaluation checklists, pharmacy dispensing records, 
recorded data from automated instruments, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, subject files and records kept at the pharmacy, at the laboratory and at 
the medico-technical departments involved in the clinical study) which contain the source of 
data recorded in the CRF should be specified.  The CRF and/or diary can be used as a source 
document at the discretion of data management. 
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number. 
11.1 
Case Report Form 
A CRF is a printed, optical, or electronic document designed to record the protocol required 
information to be reported to the sponsor on each trial subject. 
For each subject who has given informed consent/assent the CRF must be completed and signed 
by the Principal Investigator (or authorized designee) to certify that the data are complete and 
correct.  The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Management of clinical data will be performed in accordance with Third Party BDM Vendor 
applicable standards and data cleaning procedures with oversight by GSK CH to ensure 
integrity of the data, for example, to remove errors and inconsistencies in the data.  
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To protect the privacy of subjects, no Personally Identifiable Information (PII) (including the 
subject's name or initials or full birth date) is to be recorded in the CRF or as part of the query 
text. 
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.   
GSK CH will obtain and retain all CRFs and associated study data as applicable at the 
completion of the study.  
11.2 
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. 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
and any concomitant medications terms (if applicable) using an internal validated medication 
dictionary, GSKDrug.   
11.2.1 
Data Queries 
Programmed edit checks will be generated automatically, as the data are being entered into the 
system. Reports and listings on the CRF data will also be run, 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 (AEs and Drugs or concomitant 
medication) appropriately.  
The study monitor will perform ongoing review the of the CRFs in accordance with the 
monitoring plan, to confirm that data entered into the CRF by authorized site personnel are 
accurate, complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
Any queries will be generated in the EDC System to the Investigator or designee, enabling the 
errors to be addressed in parallel with Data Management review. The study monitor can also 
run reports and listings on the CRFs, to raise manual queries as needed for site clarification or 
correction. 
11.3 
Processing Patient Reported Outcomes 
Paper based patient reported outcome (PRO) data will be collected from a diary, questionnaire, 
or other specified document, etc. and entered into the data management system (DMS).   
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Electronic Patient reported outcome (ePRO) data may be collected using electronic devices and 
transferred electronically to GSKCH or Third-party DM vendor. ePRO will not be used for this 
study. 
All PRO source data should be reviewed by the study staff and the study monitor to ensure 
accurate transcription of data and that any potential AEs or concomitant medications reported 
on these documents are discussed with the subject and transcribed accurately to the CRF and/or 
DMS.  PROs that are classed as source data will be retained by the investigator and true/certified 
copies may be sent to a designated vendor or GSK CH as required. 
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 any PRO/ePRO that will be 
forwarded to GSK CH or Third-Party Vendor. 
11.4 
External Data  
External Data are subject data obtained externally to the CRF. These data are generated from 
laboratory instruments, computers or other sources and then transcribed into a file and format 
agreed upon by GSK CH to identify the subject and time point referenced in the CRF and/or 
protocol.  
An agreed quality control process will be performed against the transcribed data to the source 
to ensure the accuracy of the transcription. The transcribed data is transmitted in an agreed upon 
format to GSK CH.  
Reconciliation will be performed between the transcribed data and the clinical database to 
ensure subject and time point referenced in the Clinical Database match before Clinical 
Database Freeze (locking of the database) can occur. 
12 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES. 
12.1 
Sample Size Determination 
No formal study powering was conducted. Forty (40) randomized subjects per treatment group 
are deemed to be sufficient for generating sufficient efficacy and safety data to evaluate the 
combination product (sodium bicarbonate and sodium hyaluronate), with sodium bicarbonate 
dentifrice and regular fluoride dentifrice in this PoP study.  
Sufficient subjects will be screened (approximately 160) by the study site so that at least 120 
subjects (approximately 40 per treatment group) who fulfill all the entry criteria will be 
randomized, which should ensure that approximately 36 evaluable subjects per group complete 
the week 6 assessment (thus allowing for a 10% drop-out rate).  
12.2 
Statistical Methods and Analytical Plan 
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written following finalization of the protocol 
and prior to study unblinding. 
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12.2.1 
Definition of Analysis Populations 
The Safety population will include all randomized subjects who receive at least one dose of 
study product. This population will be based on the product the subject received. 
The modified Intent-To-Treat (mITT) population will include all randomized subjects who 
receive at least one dose of study product and have at least one post baseline (post treatment) 
efficacy measurement. This population will be based on the study product to which the subject 
was randomized. Any subject who receives a randomization number will be considered to have 
been randomized. 
The Per Protocol (PP) population includes all mITT subjects who fully comply with all study 
procedures and restrictions. Violations excluding from PP population will be determined and 
applied prior to unblinding and consist of variations in criteria likely to affect the interpretation 
of the efficacy parameters. 
The repeatability population for MGI is defined as all subjects who have at least one repeat 
MGI clinical assessment at any visit. 
The repeatability population for TPI is defined as all subjects who have at least one repeat TPI 
clinical assessment at any visit. 
12.2.2 
Exclusion of Data from Analysis  
Protocol violations considered to have had affected efficacy will lead to exclusion of either 
subject or data from PP analyses. Exclusion of any data from the analyses will be determined 
during a Blind Data Review (BDR) Meeting prior to database lock. Any reasons for exclusion 
from an analysis population will be listed, if applicable.  
A PP analysis will be performed only if 10% or more mITT subjects are excluded from PP 
population. A decision on whether a PP analysis will be performed will be made prior to study 
unblinding. 
12.2.3 
Demographic and Baseline Characteristics 
Age and other continuous variables will be summarized using descriptive statistics such as mean, 
standard deviation, median, minimum and maximum. Gender, race and other categorical 
variables will be summarized using frequency counts and percentages for the safety and mITT 
populations. 
Medical history and current medical conditions will be listed. 
12.2.4 
Study Drug/Product Compliance and Use of Other Therapies 
12.2.4.1 Study Drug/Product Compliance 
Compliance with study product use (based on number of brushings) will be summarized and 
listed for the mITT population. 
Compliance is defined as:  Compliance (%) = Actual Number of brushings / Expected Number 
of brushings ×100. 
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A threshold of compliance with allocated study treatment has been set as 80% of the 
recommended doses. Subjects with overall compliance <80% will be considered protocol 
deviations and assessed at the time of Blinded Data Review for exclusion from the Per Protocol 
(PP) population. 
12.2.4.2 Prior and Concomitant Medications 
Prior medications, concomitant medications and significant non-drug therapies taken during 
treatment will be listed for all randomized subjects. 
12.2.5 
Primary Analysis(es)  
Number of bleeding sites at 6 weeks 
The primary time point is week 6 and primary comparison will be between the 67% w/w sodium 
bicarbonate & 0.2% w/w HMW sodium hyaluronate and the fluoride control dentifrice. As there 
is only a single primary objective no adjustment for multiple comparisons is required. 
These analyses will be conducted on the mITT population.  
The primary efficacy variable is the number of bleeding sites and will be derived from the 
bleeding index, whereby a site will be considered bleeding if the bleeding index score is 1 or 2 
and will be considered not bleeding if the bleeding index score is 0.  
Summary statistics including mean, standard deviation (SD), standard error (SE), median, 
minimum, maximum will be provided by visit and randomized treatment group. Raw means 
and SE will also be plotted over time by treatment group. 
The number of bleeding sites at 6 weeks will be analyzed using an ANCOVA model with 
treatment group and gender as factors and baseline number of bleeding sites as covariate. Note 
that since the baseline number of bleeding sites will be included as a covariate, the number of 
bleeding sites stratification value will not be included in the model. 
 
Using the above model, adjusted means, along with 95% CIs will be reported by treatment 
group. Treatment difference between the 67% w/w sodium bicarbonate & 0.2% w/w HMW 
sodium hyaluronate and the fluoride control dentifrice will also be provided along with 95% 
confidence intervals. 
The assumption of residual normality and variance homogeneity in ANCOVA analysis will be 
investigated through residual plots. If violated, data transformation or a nonparametric method 
(such as van Elteren test adjusting for gender and baseline number of bleeding sites stratification) 
will be used. 
12.2.6 
Secondary Analysis(es) 
Number of bleeding sites at 6 weeks 
Using the same methodology as described above for primary analyses, pairwise treatment 
differences will be provided along with 95% confidence intervals for the following treatment 
comparisons: 
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• 67% w/w sodium bicarbonate & 0.2% w/w HMW sodium hyaluronate vs. 67% w/w 
sodium bicarbonate  
• 67% w/w sodium bicarbonate vs. fluoride control  
These analyses will be conducted on the mITT population.  
12.2.7 
Safety Analyses 
All assessments of safety will be based on the safety population.  Safety analyses will be 
performed according to the treatment that the subject received and will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA).  
AEs will be collected immediately after a subject provides consent to participate in the study 
by the completion of the informed consent form. AEs will be regarded as treatment emergent if 
they occur on or after the first treatment application. 
Treatment Emergent Adverse Events (by SOC/PT), Treatment Emergent Adverse Events 
(Oral/Non-Oral), Related Treatment Emergent AEs will be summarized by treatment.  
Deaths, Non-fatal Serious Adverse Events, Treatment Emergent Adverse Events leading to 
study or drug discontinuation, Treatment Emergent Adverse Events Classified as oral, and 
incidents will be listed. The results of the OST and OHT examinations will be listed. 
12.2.8 
Exploratory Analyses 
All the exploratory analyses described below will be conducted on the mITT population.  
Number of bleeding sites at 3 days, 1 week, 2 weeks 
The number of bleeding sites at 3 days, 1 and 2 weeks will be analyzed using same methodology 
as the primary efficacy variable described above.  
Mean Bleeding index (BI) at 3 days, 1, 2 and 6 weeks 
In addition to the primary analysis based on the number of bleeding sites, an analysis of gingival 
bleeding will be performed on the full bleeding index. The mean bleeding index will be 
calculated taking the average over all tooth sites for a subject.  
Summary statistics including mean, SD, SE, median, minimum, maximum will be provided by 
visit and randomized treatment group. Raw means and SE will also be plotted over time by 
treatment group. 
Mean BI will be analyzed using ANCOVA model with treatment group and gender and number 
of bleeding sites strata as factors, and baseline BI score as covariate. Adjusted means for all 
treatments and all pairwise treatment differences will be provided along with 95% confidence 
intervals. 
The assumption of residual normality and variance homogeneity in ANCOVA analysis will be 
investigated through residual plots. If violated, data transformation or a nonparametric method 
(such as van Elteren test adjusting for gender and baseline number of bleeding sites stratification) 
will be used. 
Mean Modified Gingival index (MGI) at 3 days, 1, 2 and 6 weeks 
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Mean MGI will be calculated taking the average over all tooth sites for a subject.  
Summary statistics including mean, SD, SE, median, minimum, maximum will be provided by 
visit and randomized treatment group. Raw means and SE will also be plotted over time by 
treatment group. 
Mean MGI score will be analyzed using ANCOVA model with treatment group, gender and 
number of bleeding sites strata as factors and baseline MGI score as covariate. Adjusted means 
for all treatments and all pairwise treatment differences will be provided along with 95% 
confidence intervals. 
The assumption of residual normality and variance homogeneity in ANCOVA analysis will be 
investigated through residual plots. If violated, data transformation or a nonparametric method 
(such as van Elteren test adjusting for gender and baseline number of bleeding sites stratification) 
will be used. 
Mean Plaque index (TPI) (overall and interproximal) at 3 days, 1, 2 and 6 weeks 
Mean overall plaque will be calculated taking the average over all tooth sites for a subject.  
The interproximal plaque score will be calculated in the same way as for the overall scores but 
just based on the mesiofacial, distofacial, mesiolingual and distolingual surfaces.  
Summary statistics including mean, SD, SE, median, minimum, maximum will be provided by 
visit and randomized treatment group for overall plaque and interproximal plaque. Raw means 
and SE will also be plotted over time by treatment group. 
Overall plaque score and interproximal plaque score will be analyzed using ANCOVA model 
with treatment group, gender and number of bleeding sites strata as factors and baseline plaque 
score as covariate. 
Adjusted means for all treatments and all pairwise treatment differences will be provided along 
with 95% confidence intervals. 
The assumption of residual normality and variance homogeneity in ANCOVA analysis will be 
investigated through residual plots. If violated, data transformation or a nonparametric method 
(such as van Elteren test adjusting for gender and baseline number of bleeding sites stratification) 
will be used. 
Subgroups analyses – Mean MGI and Mean BI at 3 days, 1, 2 and 6 weeks 
A subgroup analysis to evaluate and compare mean MGI and number of bleeding sites in low 
(<45) and high (≥45) bleeding sites groups will be conducted using the same methodology as 
described above for each respective endpoint. 
12.2.9 
Other Analyses 
Repeatability of the examiner  
The repeatability of the examiner in conducting the MGI and TPI assessments will also be 
performed. The repeat plaque and MGI assessments will be compared to the original 
assessments. The repeat assessment is not to be used in any efficacy analysis. The first and 
second assessments will be cross tabulated.  
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A weighted Kappa coefficient (κ), along with the 95% CI will be calculated to assess the intra-
examiner reliability. Fleiss-Cohen weighted kappa will be calculated for the repeatability 
analysis. Reliability will be deemed 
• Excellent if κ > 0.75 
• Fair to good if 0.4 ≤ κ ≤ 0.75 
• Poor if κ <0.4 
This analysis will be conducted on each respective index repeatability population (MGI 
population and TPI population). 
12.2.10 Handling of Dropouts and Missing Data  
Subjects who withdraw from the study early will be included in the study analysis up to the 
point of withdrawal. Subjects who withdraw will not be replaced. No data will be imputed in 
the case of dropouts or missing data. 
12.2.11 Interim Analysis  
No interim analysis is planned for this study 
13 
STUDY GOVERNANCE CONSIDERATIONS 
13.1 
Quality Control  
In accordance with applicable regulations including GCP, and GSK CH procedures, GSK CH 
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 CH 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 CH or designee will monitor the study and site activity to verify that the: 
• Data are authentic, accurate, and complete. 
• Safety and rights of subjects are being protected. 
• Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements. 
The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all relevant 
documents and agrees to co-operate with the monitor to ensure that any problems detected in 
the course of these monitoring visits are resolved. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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13.2 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, GSK CH 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 investigator(s) will notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK CH 
or its agents to prepare the study site for the inspection and will allow GSK CH or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly apply 
copies of the inspection finding to GSK CH or its agent. Before response submission to the 
regulatory authority, the investigator will provide GSK CH or its agents with an opportunity to 
review and comment on responses to any such findings.  
The sponsor will be available to help investigators prepare for an inspection. 
13.3 
Regulatory and Ethical Considerations 
13.3.1 
Institutional Review Board/ Ethics Committee  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, investigator brochure/safety statement 
(including any updates) and other relevant documents, e.g. recruitment advertisements, if 
applicable, from the IRB/EC.  All correspondence with the IRB/EC should be retained in the 
investigator file.  Copies of IRB/EC approvals should be forwarded to GSK CH prior to the 
initiation of the study, and also when subsequent amendments to the protocol are made. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In that 
event, the investigator must notify the IRB/EC and GSK CH in writing immediately after the 
implementation. 
13.3.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical Research 
Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), 
International Ethical Guidelines for Health-Related Research Involving Humans (Council for 
International Organizations of Medical Sciences, 2016), guidelines for GCP (ICH 1996 and 
revision 2), and the Declaration of Helsinki (World Medical Association 2013).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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13.3.3 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names or 
other identifiable data in any reports, publications, or other disclosures, except where required 
by laws.  
When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects.   
The study site will maintain a confidential list of subjects who participated in the study, linking 
each subject’s numerical code to his or her actual identity.  In case of data transfer, GSK CH 
will maintain high standards of confidentiality and protection of subjects’ personal data 
consistent with applicable privacy laws. 
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws. 
The informed consent documents used during the informed consent process must be reviewed 
and approved by the sponsor, approved by the IRB/EC before use, and available for inspection. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. A member of clinical 
study site personnel not involved in providing subject care, or conduct of any of the dental 
assessments will be responsible for obtaining written informed consent from each subject before 
any study-specific activity is performed.  The investigator will retain the original of each 
subject's signed informed consent document. 
13.3.4 
Subject Recruitment  
Advertisements approved by IRBs/ECs and investigator databases may be used as recruitment 
procedures.  Use of ethics committee approved, generic, prescreening questionnaire to assess 
basic subject characteristics to determine general eligibility for this study is allowed.  This 
generic questionnaire may be used by sites as a phone script and/or to review internal databases 
to identify subjects.   
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used.  
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP  
Within GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH-sponsored human subject research studies.  
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSK CH should be informed immediately.  
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
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In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13.4 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial registers 
before enrollment of subjects begins in accordance with applicable GSK CH processes. 
GSK intends to make anonymized subject-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding 
13.5 
Provision of Study Results to Investigators 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the opportunity 
to review the complete study results at a GSK CH site or other mutually-agreeable location. 
GSK CH 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 CH Policy. 
A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge. 
13.6 
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 CH audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site staff. 
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g. microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions. 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 7 1  of 7 7  
T he i n vesti gat or m ust ass ure t hat t he s u bject’s a n o n y mit y will be mai ntai ne d.  O n C R Fs or ot her 
d oc u me nts s u b mitte d t o G S K C H, s u bjects s h o ul d n ot be i de ntifie d b y t heir na mes or i nitials, 
b ut b y a n i de ntificati o n c o de. T he i n vesti gat or s h o ul d kee p a se parate l o g of s u bjects’ c o des, 
na mes a n d a d dress es.  D o c u me nts n ot f or s u b missi o n t o G S K C H, e. g. s u bjects’ writte n c o ns e nt 
f or ms, s h o ul d be mai ntai ne d b y t h e i n vesti gat or i n strict c o nfi de nce. 
Rec or ds a n d d o c u me nts, i ncl u d i n g si g ne d I C F, pertai ni n g t o t he c o n d uct of t his st u d y m ust be 
retai ne d b y t he i n vesti gat or f or 2 5 years fr o m t he iss ue of t he fi nal Cli nical St u d y Re p ort ( C S R) 
or e q ui vale nt s u m mar y,  u nless l ocal re g ul ati o ns or i nstit uti o nal p olicies re q uir e a l o n ger 
rete nti o n peri o d. T he mi ni m u m rete nti o n ti me will meet t he strictest sta n dar d a p plica ble t o t hat 
site f or t he st u d y, as dictate d b y a n y i nstit uti o nal re q uire me nts or l ocal la ws or re g ulati o ns, G S K 
C H sta n dar ds/ pr oce d ures, a n d/ or i nstit uti o nal re q uire me nts.   
N o st u d y d o c u me nt s h o ul d be destr o ye d wit h o ut a pri or writte n a gree m e nt bet wee n G S K C H 
a n d t he i n vesti gat or. T h e i n vesti gat or m ust n otif y G S K C H of a n y c h a n ges i n t he arc hi val 
arra n ge me nts, i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off -site facilit y or tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he site.  
1 3. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y  
Pre mat ure ter mi nati o n of t his st u d y ma y o cc ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or st u d y pr o d uct safet y pr o ble ms, or at t he discreti o n of G S K 
C H.  I n a d diti o n, G S K C H retai ns t he ri g ht t o disc o nti n ue de vel o p me nt of t he i n vesti gati o nal 
pr o d uct  at a n y ti me. F or m ultice nter st u dies (if a p plica ble), t his ca n occ ur at o ne or m o re or at 
all sites.   
If a st u d y is pre mat urel y t er mi nate d, G S K C H will pr o m ptl y n otif y t h e i n vesti gat or.  After 
n otificati o n, t he i n vesti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bjects a n d s h o ul d ass ur e 
a p pr o priate t hera p y/ f oll o w -u p f or t he s u bjec ts.  As directe d b y G S K C H, all st u d y materials 
m ust be c ollecte d a n d all  C R Fs  c o m plete d t o t he greatest e xte nt p ossi ble. W here re q uire d b y 
t he a p plica ble re g ulat or y re q uir e me nts, G S K C H s h o ul d i nf or m t he re g ul at or y a ut h orit y(ies) 
a n d t he i n vesti gat or s h o u l d pr o m ptl y i nf or m t he I R B/ E C a n d pr o vi de t h e I R B/ E C a detaile d 
writte n e x pla nati o n of t he ter mi nati o n or s us pe nsi o n.  
If t h e I R B/ E C ter mi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni o n of a trial, t he i n vesti gat or 
s h o ul d pr o m ptl y n otif y t he G S K C H a n d pr o vi de G S K C H wit h a detaile d writte n e x pla nati o n 
of t he ter mi nati o n or s us pe nsi o n.  
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, t he G S K C H m o nit or will c o n d uct 
site cl os ure acti vities wit h t he i n vesti gat or or site staff, as a p pr o priate, i n acc or da nce wit h 
a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K C H Sta n dar d O perati n g Pr oce d ures.  
1 4  
R E F E R E N C E S  
A v ail a ble o n re q uest  
 
 
  
 
  
 
  
 
 
. 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 7 2  of 7 7  
 
 
 
 
 
 
 
 
 
  
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 7 3  of 7 7  
 
 
 
 
 
 
  
 
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 0 8 1 7 5 
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S KC H  
S P 1 9 6 3/ S O P -2 0 8 6 6 1: Te m plate Versi o n: 1 4 Mar 2 0 1 9  
Pa ge 7 4  of 7 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 0 8 1 7 5 | Pr ot oc ol 2 0 8 1 7 5 Cli nical Pr ot oc ol 0 7 Fe b 2 0 2 1 | T M F- 4 8 0 6 8 | 4. 0
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 75 of 77 
15 
APPENDICIES 
15.1 
Product Usage Instructions 
INSTRUCTIONS 
Brush twice a day (morning and evening) for 1 timed minute. 
Each time you brush: 
• Dispense a ribbon of toothpaste covering the entire length of the toothbrush head (see 
picture below). 
• Set your timer for 1 minute, and then brush all the teeth in your mouth in your usual 
manner for 1 timed minute. 
• Please record each brushing in the diary. Note any changes to these brushing procedures 
and reasons for changes (e.g. missed brushings, extra brushings). 
• On the day before your next visit, please record the actual time of your last brushing 
before attending site. Please remember do not brush your teeth within 12 hours (+6 
hours, -2 hours) before your scheduled study assessment visits.  
• Please record any changes to your health, medications (prescription and over the counter 
medications) or treatments in the diary.  
• Please bring your diary card (completed and not completed), toothpaste and toothbrush 
to the next study visit. 
• Please do not remove or deface any part of the study label. 
Please do not share your study toothpaste with anybody and do not discuss with the 
examiner your experience with your assigned toothpaste (e.g. taste, color or smell). 
 
 
 
 
 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 76 of 77 
15.2 
ABBREVIATIONS 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviations 
Abbreviation 
Term 
AE 
adverse event 
ANCOVA 
analysis of covariance 
BDM 
Biostatistics and Data Management 
BDS 
Bachelor of Dental Surgery 
BI 
Bleeding index 
CI 
confidence interval 
CRF 
case report form 
CRS 
Clinical Research Scientist 
CSR 
Clinical study report 
Da 
Dalton 
DMS 
Data management system 
EC 
ethics committee 
ECG 
echocardiogram 
EDC 
Electronic data capture 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FSFV 
First subject first visit 
FSH 
Follicle-stimulating hormone 
GCF 
Gingival crevicular fluid 
GCP 
 
Good Clinical Practice 
GSK CH 
GlaxoSmithKline Consumer Healthcare 
HA 
hyaluronic acid (sodium hyaluronate) 
HMW 
High molecular weight 
hrs 
hours 
IB 
investigator’s brochure 
ICH 
International Conference on Harmonisation 
IND 
investigational new drug application 
IRB 
institutional review board 
ITT 
Intent to treat 
IUD 
intrauterine device 
LLC 
limited liability company 
MedDRA 
medical Dictionary for Regulatory Activities 
MFC 
Master formulation code 
MGI 
Modified gingival index 
mm 
Millimeter 
MW 
Molecular weight 
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Clinical Protocol 
 
 
Protocol Number: 208175 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SP1963/SOP-208661: Template Version: 14 Mar 2019 
Page 77 of 77 
Abbreviation 
Term 
N/A 
not applicable 
No. 
Number 
NJ 
New Jersey 
NNHP 
Non-prescription Natural Health Product 
OHT 
Oral hard tissue 
OST 
Oral soft tissue 
PI 
principal investigator 
PII 
Personally identifiable information 
PoP 
Proof-of-principle 
PP 
Per protocol 
PRO 
Patient reported outcome 
RAP 
Reporting and analysis plan 
SAE 
serious adverse event 
SD 
Standard deviation 
SE 
Standard error 
SOP 
standard operating procedure 
SRSD 
single reference study document 
SS 
safety statement 
SUSAR 
Suspected unexpected serious adverse reaction 
TPI 
Turesky modification of the Quigley Hein Plaque Index 
UK 
United Kingdom 
UPT 
Urine pregnancy test 
US 
United States 
w/w 
Weight for weight 
 
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