A Randomized, Controlled Clinical Study to Evaluate the Efficacy of a Range of Dental/Denture Products for Improved Oral Health, Compared to Existing Oral Hygiene, in a Population of Partial Denture Wearers With Generalized Mild-moderate Plaque-induced Gingivitis
Phase: PHASE4
Conditions: Gingivitis
Sponsor: HALEON

C LI NI C A L P R O T O C O L  
A r a n d o mi z e d, c o ntr oll e d cli ni c al st u d y t o e v al u at e t h e effi c a c y of a 
r a n g e of d e nt al/ d e nt ur e pr o d u ct s f or i m pr o v e d or al h e alt h, 
c o m p ar e d t o e xi sti n g or al h y gi e n e, i n a p o p ul ati o n of p arti al d e nt ur e 
w e ar er s wit h g e n er ali z e d mil d -m o d er at e pl a q u e -i n d u c e d gi n gi viti s 
Pr ot o c ol N u m b er:  
2 1 2 4 0 1  
C o m p o u n d/ Pr o d u ct N a m e:  
D e nt al/ D e nt ur e Cl e a n si n g R a n g e  
U nit e d St at e s ( U S) I n v e sti g ati o n al 
N e w Dr u g (I N D) N u m b er:  
N/ A  
E ur o p e a n Cli ni c al Tri al s D at a b a s e 
( E u dr a C T) N u m b er: 
N/ A  
Ot h er R e g ul at or y A g e n c y I d e ntifi e d 
N u m b er:  
N/ A  
P h a s e:  
I V 
S p o n s or I nf or m ati o n  
S p o n s or N a m e & L e g al R e gi st er e d 
A d dr e s s  
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e ( U K) 
Tr a di n g Li mit e d  
S p o n s or C o nt a ct D et ail s  
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e ( G S K 
C H)  
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
T hi s d o c u m e nt c o nt ai n s c o nfi d e nti alit y st at e m e nt s t h at ar e n ot r el e v a nt f or t hi s 
p u bli cl y a v ail a bl e v er si o n
P P D
P P D

Document History 
 
Document 
Version Summary of Changes  
Original protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
2.0 
Removal of microbiology endpoints 
Addition of oral hygiene index endpoints 
Change in product usage instructions (for foam) to align with new 
GDS 
Update to inclusion/exclusion criteria. 
Change in overall language to align with study running in UK 
rather than US. 
Change in PDCI objective from exploratory to secondary 
Amendment 2 
3.0 
Change in diary dispensation which will now only be performed 
once. 
Correction of the descriptive terms in Table 9.6. 
Reinstatement of Lifestyle Consideration regarding interproximal 
cleaning. 
Clarification in study design that subjects should have only 1 
RPD. 
Clarification in section 12.2.3 that Medical history will be listed 
rather than tabulated. 
Removal of requirement for daily text messages reminding 
subjects to use treatment products. 
Correction of stability criterion in section 9.1.4. 
Amendment 3 
4.0 
Addition of oral care advice to be given to all randomized subjects 
at Visit 2 (section 8.2.1). 
Definition of mITT included in Synopsis 
Changes to compliance text (section 6.7) to clarify that failure to 
follow the oral care advice given at Visit 2 (as detailed in section 
8.2.1) will not qualify as a deviation. 
Change to compliance text (section 6.7) to clarify that for subjects 
in the non-intervention group, a deviation will be recorded if, in 
the opinion of the investigator or designee, they significantly and 
consistently change their oral hygiene routine. 
Clarification in instructions for use and sections 4 and 6 that 
subjects will use treatment products twice per day. 
Clarification in section 12.2.8 that photographs of RPDs will be 
included in the clinical report for illustration of the scale only. 
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.   
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

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 nd 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 erso 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 st u 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 researc 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: 
 
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 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
P P D
P P D
P P D

Table of Contents 
Sponsor Information ............................................................................................................ 1 
Document History ............................................................................................................... 2 
Principal Investigator Protocol Agreement Page ................................................................ 3 
Table of Contents ................................................................................................................ 4 
1 
PROTOCOL SUMMARY .................................................................................................. 8 
1.1 
Schedule of Activities ............................................................................................ 12 
2 
INTRODUCTION ............................................................................................................. 14 
2.1 
Study Rationale ...................................................................................................... 15 
2.2 
Background ............................................................................................................ 16 
2.3 
Mechanism of Action/Indication ........................................................................... 16 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 17 
4 
STUDY DESIGN .............................................................................................................. 19 
4.1 
Overall Design ....................................................................................................... 19 
4.2 
Rationale for Study Design .................................................................................... 21 
4.3 
Justification for Dose ............................................................................................. 23 
4.4 
End of Study Definition ......................................................................................... 24 
5 
STUDY POPULATION .................................................................................................... 24 
5.1 
Type and Planned Number of Subjects ................................................................. 24 
5.2 
Inclusion Criteria ................................................................................................... 25 
5.3 
Exclusion Criteria .................................................................................................. 25 
5.4 
Randomization Criteria .......................................................................................... 27 
5.5 
Lifestyle Considerations ........................................................................................ 27 
5.5.1 
During the entire study (screening – subject’s last study visit): ........... 27 
5.5.2 
Prior to Visits 2, 3 and 4: ...................................................................... 28 
5.6 
Screen Failures....................................................................................................... 28 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 28 
5.8 
Rater/Clinical Assessor Qualifications .................................................................. 29 
6 
INVESTIGATIONAL/STUDY PRODUCTS................................................................... 29 
6.1 
Investigational/Study Product Supplies ................................................................. 29 
6.1.1 
Dosage Form and Packaging ................................................................. 31 
6.1.2 
Preparation and Dispensing................................................................... 32 
6.2 
Administration ....................................................................................................... 32 
6.2.1 
Medication/Dosing Errors ..................................................................... 32 
6.2.2 
Overdose ............................................................................................... 33 
6.3 
Investigational/Study Product Storage .................................................................. 33 
6.4 
Investigational/Study Product Accountability ....................................................... 34 
6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 34 
6.5 
Blinding and Allocation/Randomization ............................................................... 34 
6.6 
Breaking the Blind ................................................................................................. 35 
6.7 
Compliance ............................................................................................................ 35 
6.8 
Concomitant Medication/Treatment(s) .................................................................. 36 
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7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................... 36 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 36 
7.2 
Lost to Follow up ................................................................................................... 37 
8 
STUDY PROCEDURES ................................................................................................... 37 
8.1 
Visit 1/Screening ................................................................................................... 37 
8.1.1 
Screening Procedures ............................................................................ 38 
8.2 
Study Period .......................................................................................................... 39 
8.2.1 
Visit 2/Day 0 – Baseline ....................................................................... 39 
8.2.2 
Visit 3/Day 42 ±3 .................................................................................. 40 
8.2.3 
Visit 4 /Day 84 ±3 ................................................................................. 41 
8.2.4 
Study Procedures ................................................................................... 42 
8.2.5 
Photography of RPD – subset of subjects only ..................................... 42 
8.2.6 
Inclusion/Exclusion Criteria ................................................................. 43 
8.2.7 
Supervised Product Application ............................................................ 43 
8.2.8 
Dental Prophylaxis and RPD Cleansing ............................................... 43 
8.2.9 
Study Conclusion .................................................................................. 43 
8.2.10 
Follow-up Visit / Phone Call ................................................................ 44 
9 
STUDY ASSESSMENTS ................................................................................................. 44 
9.1 
Screening Assessments .......................................................................................... 44 
9.1.1 
OST Examination .................................................................................. 44 
9.1.2 
OHT Examination ................................................................................. 44 
9.1.3 
Gross Gingival Health Assessment ....................................................... 44 
9.1.4 
Evaluation of Well Fit Partial Denture.................................................. 44 
9.1.5 
Criteria for a Well Made Removable Partial Denture ........................... 45 
9.2 
Efficacy Assessments ............................................................................................ 45 
9.2.1 
Subject Questionnaire ........................................................................... 46 
9.2.2 
Partial Denture Cleanliness Index (PDCI) ............................................ 46 
9.2.3 
Modified Gingival Index (MGI) ........................................................... 46 
9.2.4 
Bleeding Index (BI)............................................................................... 47 
9.2.5 
Turesky Plaque Index (TPI) .................................................................. 48 
9.2.6 
Oral Hygiene Index ............................................................................... 48 
9.3 
Safety and Other Assessments ............................................................................... 50 
9.3.1 
Oral Soft Tissue Examination (OST) .................................................... 50 
9.3.2 
Oral Hard Tissue Examination (OHT) .................................................. 51 
9.3.3 
Repeatability Assessments – subset of subjects only ............................ 51 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS ........................................... 51 
10.1 
Definition of an Adverse Event (AE) .................................................................... 51 
10.2 
Definition of a Serious Adverse Event (SAE) ....................................................... 52 
10.3 
Reporting of Adverse Events ................................................................................. 53 
10.3.1 
Reporting Period ................................................................................... 53 
10.4 
Reporting Procedures............................................................................................. 54 
10.4.1 
Reporting of an Adverse Event ............................................................. 54 
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10.4.2 
Reporting of a Serious Adverse Event .................................................. 55 
10.5 
Evaluating Adverse Events .................................................................................... 56 
10.5.1 
Assessment of Intensity ........................................................................ 56 
10.5.2 
Assessment of Causality ....................................................................... 56 
10.6 
Follow-up of Adverse Events ................................................................................ 57 
10.7 
Withdrawal Due to an Adverse Event ................................................................... 57 
10.7.1 
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees ................................................................................ 57 
10.8 
Pregnancy .............................................................................................................. 58 
10.8.1 
Time Period for Collecting Pregnancy Information.............................. 58 
10.8.2 
Action to be Taken if Pregnancy Occurs .............................................. 58 
10.9 
Definition of and Procedure for Reporting Medical Device Incidents .................. 58 
10.9.1 
Definition of an Incident ....................................................................... 58 
10.9.2 
Reporting of Incidents and Malfunctions .............................................. 59 
10.9.3 
Follow-up of Medical Device Incidents ................................................ 60 
10.9.4 
Regulatory and Ethics Reporting Requirements for Incidents .............. 60 
11 DATA MANAGEMENT .................................................................................................. 61 
11.1 
Case Report Form .................................................................................................. 61 
11.2 
Data Handling ........................................................................................................ 61 
11.2.1 
Data Queries .......................................................................................... 62 
11.3 
Processing Patient Reported Outcomes ................................................................. 62 
11.4 
External Data ......................................................................................................... 62 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................. 63 
12.1 
Sample Size Determination ................................................................................... 63 
12.2 
Statistical Methods and Analytical Plan ................................................................ 63 
12.2.1 
Definition of Analysis Populations ....................................................... 63 
12.2.2 
Exclusion of Data from Analysis .......................................................... 64 
12.2.3 
Demographic and Baseline Characteristics ........................................... 64 
12.2.4 
Study Drug/Product Compliance and Use of Other Therapies ............. 64 
12.2.5 
Primary Analysis ................................................................................... 64 
12.2.6 
Secondary Analyses .............................................................................. 65 
12.2.7 
Safety Analysis ..................................................................................... 66 
12.2.8 
Exploratory Analyses ............................................................................ 66 
12.2.9 
Other Analyses ...................................................................................... 67 
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 ................................................................ 69 
13.3.3 
Subject Information and Consent .......................................................... 69 
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13.3.4 
Subject Recruitment .............................................................................. 69 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 70 
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 .................................................................................................................. 72 
15 Appendix ........................................................................................................................... 77 
15.1 
Abbreviations ......................................................................................................... 77 
15.2 
Product Usage Instructions .................................................................................... 79 
15.3 
Dental History ........................................................................................................ 80 
List of in text tables 
Table 1-1 
Schedule of Activities ........................................................................... 12 
Table 3-1 
Study Objectives and Endpoints ........................................................... 17 
Table 6-1 
Investigational/Study Product Supplies ................................................ 30 
Table 6-2 
Sundry Items ......................................................................................... 30 
Table 9-1 
The Partial Denture Cleanliness Index (PDCI) from (Blair et al, 
1995). .................................................................................................... 46 
Table 9-2 
The Modified Gingival Index (MGI) .................................................... 47 
Table 9-3 
The Bleeding Index (BI) ....................................................................... 47 
Table 9-4 
Turesky Plaque Index ............................................................................ 48 
Table 9-5 
The calculus index – from (Greene and Vermillion, 1960) .................. 49 
Table 9-6 
The oral debris index – from (Greene and Vermillion, 1960) .............. 50 
Table 15-1 
Abbreviation .......................................................................................... 77 
 
 
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1 
PROTOCOL SUMMARY  
Background and Rationale 
The study will examine the effects of an intervention with a range of dental/denture products 
(comprising use of 3 products, a dentifrice, a mouthrinse and a denture cleanser) compared to 
no intervention (use of existing oral hygiene) in a population with mild-moderate generalized 
gum problems and who wear a removable partial denture (RPD).  The study will evaluate 
subjects’ oral and gum health using established clinical indices for gingivitis, plaque and oral 
hygiene endpoints, denture cleanliness will be assessed by the partial denture cleanliness index 
and subjects’ perceptions towards dental/denture cleaning will be explored via a questionnaire.  
This study is required to support the efficacy and safety of the sequential use of these 3 products. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gingival bleeding 
(following dental prophylaxis), as measured by the Bleeding Index 
(BI), compared to no intervention (existing oral hygiene), when used 
twice daily for 12 weeks. 
BI at 12 weeks. 
Secondary 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gingival bleeding 
(following dental prophylaxis), as measured by the number of 
bleeding sites, compared to no intervention (existing oral hygiene), 
when used twice daily for 6 and 12 weeks. 
Number of bleeding sites at 
6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gingival 
inflammation (following dental prophylaxis), as measured by the 
Modified Gingival Index (MGI), compared to no intervention (existing 
oral hygiene), when used twice daily for 6 and 12 weeks. 
MGI at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival plaque formation (following 
dental prophylaxis), as measured by the Turesky Plaque Index 
(TPI), compared to no intervention (existing oral hygiene), when 
used twice daily for 6 and 12 weeks. 
TPI (overall and 
interproximal) at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gingival bleeding 
(following dental prophylaxis), as measured by the Bleeding Index, 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 weeks. 
BI at 6 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining the cleanliness of partial dentures, as 
measured by the Partial Denture Cleanliness Index (PDCI), 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
PDCI scores at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival calculus formation (following 
dental prophylaxis), as measured by the calculus index 
(CI)component of the oral hygiene index (OHI), compared to no 
intervention (existing oral hygiene), when used twice daily for 6 and 
12 weeks. 
CI scores at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing oral debris (following dental prophylaxis), as 
measured by the oral debris index component of the OHI, compared 
to no intervention (existing oral hygiene), when used twice daily for 6 
and 12 weeks. 
ODI scores at 6 and 12 
weeks. 
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To evaluate the clinical efficacy of a range of dental/denture 
products in improving oral hygiene (following dental prophylaxis), as 
measured by the OHI score (composite score of calculus and oral 
debris indices), compared to no intervention (existing oral hygiene), 
when used twice daily for 6 and 12 weeks. 
OHI scores at 6 and 12 
weeks. 
Exploratory 
To evaluate subject’s perceptions of dental/denture cleaning at 6 
and 12 weeks. 
Scores from Cleaning 
Perceptions Questionnaire at 
6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the Bleeding Index, compared to no 
intervention (existing oral hygiene), when used twice daily for 6 and 
12 weeks. 
BI associated with abutment 
teeth at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the number of bleeding sites, 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
Number of bleeding sites 
associated with abutment 
teeth at 6 and 12 weeks.  
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the Modified Gingival Index, 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
MGI associated with 
abutment teeth at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival plaque formation associated 
with denture abutment teeth (following dental prophylaxis), as 
measured by the modified Turesky Plaque Index, compared to no 
intervention (existing oral hygiene), when used twice daily for 6 and 
12 weeks. 
TPI associated with 
abutment teeth (overall and 
interproximal) at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival calculus formation associated 
with denture abutment teeth (following dental prophylaxis), as 
measured by the calculus index (CI) component of the oral hygiene 
index (OHI), compared to no intervention (existing oral hygiene), 
when used twice daily for 6 and 12 weeks. 
CI associated with abutment 
teeth at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing oral debris associated with denture abutment 
teeth (following dental prophylaxis), as measured by the oral debris 
index component of the OHI, compared to no intervention (existing 
oral hygiene), when used twice daily for 6 and 12 weeks. 
ODI associated with 
abutment teeth at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in improving oral hygiene associated with denture 
abutment teeth (following dental prophylaxis), as measured by the 
OHI score (composite score of calculus and oral debris indices), 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
OHI associated with 
abutment teeth at 6 and 12 
weeks. 
To capture photographic images of RPDs for each of the scores in 
the PDCI scale to assist study site staff with consistent evaluation of 
the PDCI over the duration of the study, to assist with future studies 
that might use this scale, and to aid to interpretation of results 
(including publication of the study outcomes). 
Photographs of RPDs. 
Safety 
To assess the safety and tolerability of a range of dental/denture 
products when used twice daily for 12 weeks. 
Treatment emergent adverse 
events and incidents. 
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Study Design 
This will be a single-center, single-blind (to the examiner(s) performing the plaque, gingivitis, 
denture cleanliness and oral hygiene assessments), randomized, stratified (by denture material 
type and baseline mean overall MGI score), two-treatment, parallel group, 12 week clinical 
study in generally healthy, adult volunteers with one conventional RPD and generalized, mild-
moderate, plaque-induced gingivitis (as determined by clinical examiner) and ≥4 natural teeth 
in each arch that meet all study criteria at both the Screening and Baseline visits (including ≥ 
30 evaluable surfaces for clinical evaluation of gingivitis and plaque).  The study will examine 
the effects of twice daily use of a range of dental/denture products (comprising use of a 
dentifrice, a mouthrinse and a denture cleanser) compared to no intervention (subjects who 
continue with their existing oral hygiene habits).  There will be four visits to the study site: 
Screening, Baseline (when subjects are randomized), and after 6- and 12-Weeks use of the range 
of dental/denture products.  Gingivitis will be assessed using the Modified Gingival Index (MGI) 
(Lobene, 1986) and a Bleeding Index (BI) (Saxton and Ouderaa, 1989).  Plaque will be assessed 
by the Turesky modification of the Quigley & Hein Plaque Index (TPI) (Lobene et al, 1982).  
These indices are intended as markers of overall oral health.  The cleanliness of the denture will 
be assessed by the examiner using the Partial Denture Cleanliness Index (PDCI) and overall 
oral hygiene will be assessed by the Oral Hygiene Index (OHI) (Greene and Vermillion, 1960).  
The subject’s perception of denture/dental cleanliness will be determined through a 
questionnaire.  Safety will be assessed through examination of the subject’s oral hard and soft 
tissues throughout the study, recorded AEs and Incidents. 
Study Products 
Usage of a range of dental/denture products comprising of: 
• Experimental dentifrice containing 0.454% stannous fluoride (currently non-marketed) 
• A strip of the dentifrice (full brush head) will be applied to the full length of the 
toothbrush head and used to brush the teeth for 2 timed minutes. 
• Denture cleansing foam (COREGA Purfrisch Reinigungsschaum - German Marketplace 
product). 
• The subject will clean their denture using 2 pumps of the denture cleansing foam and 
a denture cleaning brush for 90 timed seconds outside of the mouth. 
• Experimental mouthrinse containing 90ppm fluoride as sodium fluoride (currently non-
marketed) 
• 10ml of the mouthrinse will then be swished around the mouth for 1 timed minute. 
Interventional group subjects will use the above products twice daily (morning and evening) 
for 12 weeks.  
Type and Planned Number of Subjects 
Sufficient subjects will be screened to randomize approximately 150 (maximum 175) to ensure 
approximately 128 evaluable subjects complete the entire study.  Subjects will be generally 
healthy, have mild-moderate generalized plaque-induced gingivitis at Baseline and wear one 
conventional RPD. 
The modified intent to treat (mITT) population (defined as those subjects who are randomized, 
receive at least one dose of study product and have at least one post-baseline efficacy 
measurement performed) will be used for all primary and secondary analyses.  The primary 
efficacy endpoint will be the Bleeding Index (BI) score after 12 weeks of study treatments. The 
BI score will be calculated as the average index over all tooth sites.  An analysis of covariance 
(ANCOVA) model will be used for the primary analysis with treatment, gender, denture 
material type (acrylic or cobalt/chrome), and the baseline mean overall MGI score (low: <2.0; 
high >2.0) as factors and the baseline BI score as a covariate. The adjusted means of the two 
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treatments and the treatment difference will be provided together with 95% CI and P-values.  
The proportionate reduction will be calculated for BI and MGI endpoints. 
The null and alternative hypotheses to be tested in the primary analysis are; 
H0: There is no treatment difference in mean BI score after 12 weeks  
H1: There is a treatment difference in mean BI score after 12 weeks 
Secondary efficacy endpoints will be:  
• Number of bleeding sites at Week 6 and Week 12 
• MGI score at Week 6 and Week 12 
• Overall TPI score at Week 6 and Week 12 
• PDCI score at Week 6 and Week 12 
• Interproximal TPI score at Week 6 and Week 12 
• Overall calculus and oral debris scores and the composite OHI score at week 6 and week 
12 
• BI score at Week 6 
The BI score, MGI score, OHI score (and individual scores of calculus and oral debris) and 
overall TPI scores will be calculated as the average index values over all tooth sites. The 
interproximal TPI score will be calculated as the average index value over all interproximal 
tooth sites.  The number of bleeding sites will be calculated as the number of tooth sites with a 
BI score of 1 or 2.  The PDCI will be calculated as the average index values over all subjects. 
The number of bleeding sites, OHI score (and individual scores of calculus and oral debris), 
PDCI score, overall TPI score, interproximal TPI score, and BI score will be analyzed using an 
ANCOVA model with treatment, gender, denture material type (acrylic or cobalt/chrome), and 
baseline mean overall MGI score (low: <2.0; high >2.0) as factors and the baseline score as 
covariate. The adjusted means of the two treatments, the treatment difference and the 
proportionate reduction for each treatment group will be provided together with 95% CI and P-
values.  
The MGI score will be analyzed using an ANCOVA model with treatment, gender, denture 
material type (acrylic or cobalt/chrome) as factors and baseline MGI score as covariate. As 
baseline MGI score is included as a covariate, baseline mean overall MGI score (low: <2.0; 
high >2.0) will not be included. The adjusted means of the two treatments and the treatment 
difference will be calculated together with 95% CI and P-values.  The proportionate reduction 
will also be calculated for BI and MGI endpoints. 
For both primary and secondary analyses, the assumption of normality and homogeneity of 
variance in the ANCOVA model will be investigated and if violated, data transformations will 
be investigated. If suitable transformations cannot be found, non-parametric tests will be 
performed, and results will be compared with the ANCOVA results. If the inferences from the 
two analyses are similar, then both sets of results will be reported and emphasis will be made 
on the ANCOVA results. In case of discrepancies between inferences of the ANCOVA and 
non-parametric analysis, results will be drawn on the non-parametric analysis. 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

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, in order to conduct evaluations or assessments required to protect the 
well-being of the subject. 
Table 1-1 
Schedule of Activities 
Procedure/Assessment 
Visit 1 
1 – 28 days between Visit 1 and Visit 25 
Visit 2 
Visit 3 
Visit 4 
Screening 
(Day -28 to -1) 
Baseline 
(Day 0)1 
Week 6 
(Day 42±3)1 
Week 12 
(Day 84±3)1 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history2 
X 
 
 
 
Current / concomitant medication 
X 
X 
X 
X 
Dental history 
X 
 
 
 
Well-fit assessment of RPD 
X 
 
 
 
Collect used study products & diary 
 
 
X 
X 
Compliance checks including diary 
review 
 
 
X 
X 
Subject completes questionnaire 
 
X 
X 
X 
Remove Removable Partial Denture 
(RPD) 
X 
X 
X 
X 
Well-made assessment of RPD 
X 
 
 
 
Partial denture cleanliness index (PDCI) 
 
X 
X 
X 
Photography of RPDs representing the 
range of PDCI scores 9 
 
X 
X8 
X8 
Full oral soft tissue (OST) examination 
X3 
X 
X 
X 
Full oral hard tissue (OHT) examination 
X3 
 
 
X 
Gross gingival assessment 
X 
 
 
 
Subject continuance 
 
 
X 
X 
Modified Gingival Index (MGI) and 
Calculus Index (CI) 
 
X 
X 
X 
Disclosing followed by Plaque Index 
(TPI), Oral Debris Index (ODI) and 
Bleeding Index (BI)11 
 
X 
X 
X 
Inclusion / exclusion criteria 
X 
X 
 
 
Subject eligibility 
X 
X 
 
 
Stratification / randomization 
 
X 
 
 
Repeat MGI and TPI assessments7 
 
X 
X 
X 
RPD cleansing and sub- & supra-gingival 
prophylaxis and flossing (with second 
clinician check after disclosing & 
residual plaque removal, if applicable i.e. 
confirmed plaque score of zero) 
 
X 
 
 
Return RPD to subject 
X 
X 
X 
X 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

Dispense study products, toothbrush, 
product usage instructions, diary & 
timer4 
 
X 
X12 
 
Supervised subject brushing, mouth 
rinsing and denture cleansing at site 
including instruction in correct product 
usage6 
 
X 
X 
 
Optional dental prophylaxis and RPD 
cleansing 
 
 
 
X10 
Adverse events / incidents 
X 
X 
X 
X 
Study conclusion 
 
 
 
X 
Abbreviations: OST = Oral Soft Tissue, OHT= Oral Hard Tissue, RPD = Removable Partial Denture, TPI= Turesky Plaque 
Index, BI= Bleeding Index, MGI= Modified Gingival Index, PDCI= partial denture cleanliness index, OHI= oral hygiene index, CI= 
calculus index, ODI= oral debris index. 
Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs) and medical device incidents will be collected immediately after a 
subject provides consent to participate in the study by the completion of the Informed Consent Form (ICF). 
1. Subjects will abstain from overnight toothbrushing for a minimum of 12 hours (maximum of 18 hours) immediately prior to the assessment 
visits (Visits 2, 3 & 4). 
2. Including smoking / tobacco-use status. 
3. In relation to the general dentition exclusion criteria. 
4. Timer and diary only dispensed once, at Visit 2 only.  Subjects randomized to the no intervention group will receive only the diary.  All 
randomized subjects to receive standard oral care advice. 
5. Subjects will be instructed to brush their teeth using their normal dentifrice, use their existing denture cleansing procedure following their 
normal routine between screening and baseline visits.  
6. For subjects randomized to the interventional group only. 
7. At least 2 repeatability assessments should be performed each day (≥1 in the morning; ≥1 in the afternoon). 
8. Photographs should only be obtained at Visits 3 and 4 should insufficient photographs of sufficient quality not been obtained at Visit 2. 
9. For a subset of subjects only (in accordance with Section 8.2.5).   
10. After completion of all assessments if deemed necessary by the clinical examiner. 
11. ODI to be assessed after TPI and BI to be assessed after ODI. 
12. At Visit 3 the diary is returned to the subject following review by the study site. 
 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 212401 
 
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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2 
INTRODUCTION 
In this study, a range of products specifically for removable partial dentures (RPD) wearers to 
utilize for oral and denture cleansing will be tested for their effect in maintaining oral health.   
RPDs are considered a non-invasive and cost-effective treatment option indicated for the 
replacement of missing teeth in partially edentulous individuals.  Fixed prostheses or dental 
implants may not be available for some patients due to anatomic, systemic, or economic reasons 
(Costa et al, 2017), therefore RPDs may be considered a non-invasive and relatively cheap 
treatment with a predictable long-term success, achieving appropriate aesthetics, increasing the 
masticatory efficiency, and improving phonetics (Bohnenkamp, 2014; Nassani et al, 2013).  
However, RPDs can represent a risk for the remaining teeth, mainly abutment teeth, depending 
on the prosthesis design, health of the supporting periodontal tissues and the oral hygiene level 
(Preshaw et al, 2011).  The most common complication associated with RPDs is poor oral 
hygiene.  About 64% of RPDs wearers showed signs of poor oral hygiene in a 10-year follow-
up study (Wagner and Kern, 2000).  According to a clinical examination in another study, only 
39.8% of participants were viewed to have a good level of denture cleanliness, with the 
remaining 60.2% having a poor to moderate level (Milward et al, 2013).  RPDs have the 
potential to negatively impact on different aspects of oral health.  There is clear evidence that 
RPDs increase plaque and gingivitis (Knezovic Zlataric et al, 2003; Preshaw et al, 2011).  The 
presence of a prosthesis in the oral cavity increases the retention sites for microorganisms; this 
is particularly the case with an RPD, which has a design that favors food retention, biofilm 
accumulation and colonization of microorganisms such as Streptococcus mutans (Rocha et al, 
2008).  In a separate randomized clinical trial (Jepson et al, 2001), RPD wearers were found to 
have nearly five times more caries lesions when compared to those with fixed prostheses.  S. 
mutans and lactobacilli are found in higher levels in patients wearing RPDs than in patients 
with fixed prostheses & natural dentition (Beighton et al, 1990; Tanaka et al, 2009).  All these 
risks are more likely to affect the abutment teeth leading to potentially further tooth loss.  Kern 
and Wagner (Kern and Wagner, 2001) reported in their 10-year follow up study that 
disproportionately higher number of abutment teeth were lost over that time (26.4%) compared 
with non-abutment teeth (14.2%). 
Regular denture hygiene by individuals with RPDs is an important component of overall good 
oral health and for prevention of periodontal problems, dental caries and denture stomatitis.  It 
is therefore essential that individuals with RPDs are provided with instructions on oral and 
denture hygiene and maintenance on receiving their denture, to ensure good oral health and 
longevity of the individual’s remaining natural teeth.  However, several studies showed that 
there is a lack of knowledge surrounding denture hygiene among patients (Collis and Stafford, 
1994; de Castellucci Barbosa et al, 2008; Milward et al, 2013).  While 91.8% of study 
participants (RPD wearers) stated they were provided with instructions on denture hygiene 
when provided with their current prosthesis, 60.2% were shown to have less than an appropriate 
level of denture cleanliness (Milward et al, 2013).  Additionally, the issue of denture hygiene 
has been the focus of a Cochrane review which was unable to clearly identify the most effective 
way of removing plaque from dentures due to the paucity of available literature to answer the 
question (de Souza et al, 2009).  It is noteworthy that adherence of RPD patients to oral hygiene 
and denture hygiene instruction tends to decline as time goes by, indicating a requirement for 
continual reinforcement of oral hygiene messages (Preshaw et al, 2011).  All published RPDs 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 212401 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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guidelines emphasize on the importance of maintaining optimal oral hygiene and denture 
hygiene in RPD wearers (bsspd, 1996; Felton et al, 2011; NHS Trust, 2006; NICE, 2016). 
Gum disease describes a group of conditions affecting the periodontium (the supporting 
structures around the teeth) and includes gingivitis.  Gingivitis is an inflammatory response to 
the presence of dental plaque (Kinane, 2001), which typically presents as redness, swelling 
(edema) and/or bleeding of the gums at the gingival margin surrounding the tooth. The high 
prevalence of gingivitis worldwide is reported in large population surveys and is recognized by 
the World Health Organization (Albandar, 2002; Chapple et al, 2002; Petersen and Ogawa, 
2012).  In the USA, it has been reported in > 50% of the population, with some population 
groups approaching 100% (Brown et al, 1996; Oliver et al, 1998).  
Gingivitis is a reversible condition but, if left untreated, it can progress to the irreversible phase 
of periodontitis, where inflammation extends to the underlying tissues, periodontal ligament 
and alveolar bone. The resulting net loss of these structures can eventually lead to tooth loss 
through destruction of the periodontal tissues supporting the tooth (Petersen et al, 2005). 
Periodontitis is reported to affect 5-20% of the world’s population (Petersen et al, 2005).  The 
maintenance of good gingival health is therefore important in preventing gingivitis and the 
development of periodontal disease (Tai et al, 2006).  
Dental plaque is a soft, sticky, colourless deposit of bacteria which collects on the teeth and 
along the gingival margin; it is the causative agent of gingivitis and periodontitis (Davies, 2008; 
Kinane, 2001; Silness and Loe, 1964; Theilade et al, 1966).  Gingivitis develops when the 
plaque elicits a local inflammatory response in the gingivae at the site of its accumulation 
(Davies, 2008; Marsh, 1992).  Gingivitis is prevented and resolved through effective plaque 
control, primarily via mechanical plaque removal (i.e. toothbrushing) (Davies, 2008; Marsh, 
1992; Ower, 2003; van der Weijden and Hioe, 2005).  
In this study, a range of products specifically for RPD wearers to utilize for oral and denture 
cleansing will be tested for their effect in maintaining oral health.  Owing to the lack of clinical 
measures to probe oral health, gingivitis and plaque measurements (e.g. bleeding index, 
modified gingival index, Turesky plaque index) will be utilized as markers of general oral health.  
The product range will be used twice daily (morning and evening) and consists of a stannous 
fluoride-containing dentifrice, a sodium fluoride containing mouthrinse, and a denture cleanser 
foam.  RPD wearers are known to be high-risk for plaque accumulation, gingivitis and caries 
and this study will therefore investigate the ability of usage of the product range to reduce dental 
plaque and reduce gingivitis measures compared to a no intervention group (subjects will 
continue with their existing oral hygiene measures).  The impact of use of the product range on 
the subject’s perceptions of dental/denture cleanliness will also be explored via a questionnaire.  
This study will therefore provide the first evidence on the efficacy of a specific range of 
dental/denture products for wearers of RPD. 
2.1 
Study Rationale 
This clinical study is the first known design to explicitly investigate the efficacy and safety of 
the use of a range of dental/denture products on the maintenance of oral health.  The endpoints 
utilized in this study have been chosen as markers of general oral health of subjects who wear 
removable partial dentures.  This study is required to evaluate whether potential claims 
associated with the use of the range of dental/denture products are valid as well as to inform the 
dental practitioner on the potential benefits to oral health of the range of dental/denture products. 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 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 1 2 4 0 1 
 
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 K C 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 8 2  
 
W hilst t he pr o d uct ra n ge itself has n ot bee n pre vi o usl y cli nicall y teste d,  t he t o ot h paste a n d 
de nt ure clea ns er f oa m ha ve bee n teste d as i n di vi d ual pr o d ucts ( or pr o d ucts ver y si milar t o t h ose 
bei n g t este d) i n a n u m b er of cli nical st u dies (see Bac k gr o u n d Secti o n 2. 2 ).  T hes e st u dies 
de m o nstrate t he effic ac y a n d safet y of t he i n di vi d ual st u d y pr o d ucts.  A d diti o nal l y, t he 
e x peri me ntal de ntifrice a n d m o ut hri nse are als o ver y si milar t o e xisti n g mar kete d pr o d ucts t hat 
ha ve a n acce pta bl e ris k -b e nefit rati o.  I n c o ncl usi o n, t heref ore, t he be nefits o ut wei g h t he ris ks 
i de ntifie d f or t he i nte n de d use of t he pr o d u cts c o m prisi n g t he i nter ve nti o n al ra n ge of pr o d ucts.   
C o m plete i nf or mati o n f or t he pr o d ucts use d i n t his ra n ge of d e ntal/ de nt ure pr o d ucts ma y be 
f o u n d i n t he si n gle refere nce s afet y d o c u me nt ( S R S D), w hic h f or t his st u d y is t he safet y 
state me nt. 
2. 2  
B a c k gr o u n d  
T his st u d y is desi g ne d t o i n vesti gate t he efficac y of t he use of a pr o d uct ra n ge c o m prisi n g a 
de ntifrice, a m o ut hri nse a n d a de nt ure clea nser f oa m i n mai ntai ni n g ge neral oral healt h as 
e vi de nce d t hr o u g h i m pr o ve d si g ns of g u m healt h a n d re d uci n g pla q ue i n a p o p ulati o n of 
s u bjects w h o w ear a re m o va ble partial de nt ure.  W hilst t he se q ue ntial use of t he 3 pr o d ucts h as 
n ot bee n pre vi o usl y e v al uate d, cli nical data d o es e xist o n f or m ulati o ns ver y si milar t o t h e 
de ntifrice a n d t he de ntal clea ni n g f oa m w h e n use d i n di vi d uall y . 
T he e x peri me ntal de ntifrice c o ntai ns sta n n o us fl u ori de, a n acti ve wit h a n e xte nsi ve hist or y of 
g u m -healt h effic ac y (Ma ki n, 2 0 1 3 ; Paras ke vas a n d Va n der Weij de n, 2 0 0 6 ; R ølla a n d Elli n gse n, 
1 9 9 4 ; T wet ma n et al, 2 0 0 3 ).  Ver y si milar f or m ulati o ns t o t he e x peri me ntal de ntifrice t o be 
e val uate d i n t his st u d y ( var yi n g o nl y i n differe nces i n fla v ori n gs), ha ve bee n e val uate d 
pre vi o usl y b ot h f or d e nti ne h y p erse nsiti vit y (Par ki ns o n et al, 2 0 1 3 ; Par ki ns o n et al, 2 0 1 5 ; 
Par ki ns o n et al, 2 0 1 6 ) a n d gi n gi vitis e n d p oi nts (Par ki ns o n et al, 2 0 1 8a ; Par ki ns o n et a l, 2 0 1 8 b).  
A d diti o nall y t his f or m ulati o n has bee n s h o w n n ot t o e x hi bit de ntal stai ni n g t hat has pre vi o usl y 
bee n o bser ve d wit h sta n n o us fl u ori de -base d d e ntifrices (Ne h me et al, 2 0 1 3 ).  Sta n n o us fl u ori de 
has bee n rec o g niz e d as safe a n d effecti ve f or t he treat me nt of gi n gi vitis b y t he U S F o o d a n d 
Dr u g A d mi nistrati o n ( F D A) (F D A, 2 0 0 3 ). 
T he u sa ge of t h e mar k ete d de nt ur e clea nser f oa m has bee n cli nicall y d e m o nstrate d t o re m o v e 
de nt ure pla q u e (
) a n d de nt ur e stai n (
 
).  T h ese st u dies de m o nstrate d t he clea ni n g a bilit y of t h e cl ea nser f oa m w he n 
use d as direct e d b y br us hi n g t he f o a m o n t he de nt ure.   
2. 3  
M e c h a ni s m of A cti o n/I n di c ati o n  
De ntifrices f u ncti o n b y facilitati n g  pl a q ue re m o v al t hr o u g h t o ot h br us hi n g.  A d diti o nall y, t h e 
pr o d uct ra n ge u n der i n vesti gati o n utilizes a n e x peri me ntal de ntifrice t hat c o ntai ns Sta n n o us 
fl u ori de ( S n F2), a well-k n o w n c he m ot hera p e utic a ge nt, i nc or p orat e d i nt o de ntifrices si nce t he 
1 9 4 0s f or its oral healt h be nefits (Ma ki n, 2 0 1 3 ; Miller et al, 1 9 9 4 ; Va n L o vere n, 1 9 9 0 ; Va n 
L o vere n, 2 0 0 1 ).  T he sta n n o us i o n ( S n2 +) is a br oa d-s pectr u m a nti micr o bi al wit h bacteri ostatic 
a n d bacterici dal pr o perties (Arc hila et al, 2 0 0 4 ; Bella m y et al, 2 0 1 2 ; He et al, 2 0 1 2 ; Ti na n off, 
1 9 9 5 ).  It has bee n s h o w n t o i nterfere wit h t he de vel o p me nt a n d mat urati o n of t he pla q ue bi ofil m, 
i n hi biti n g bacterial a d here nce a n d c ol o nizati o n of t he oral s urfaces, a n d p e netrati n g t he cell wall 
t o i nterfere wit h bacteri al meta b olis m (Ti na n off, 1 9 9 0 ; Wils o n a n d Pratte n, 1 9 9 9 ).  T hes e 
effects ha ve bee n s h o w n t o carr y t hr o u g h t o i n viv o effects o n a ra n ge of micr o bial acti vities, 
res ulti n g i n a nti-pla q u e b e nefits (Bacca et al, 1 9 9 7 ; Kast uri et al, 1 9 9 5 ; W hite et al, 1 9 9 5 ). 
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 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 1 2 4 0 1 
 
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 K C 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 8 2  
 
Usa ge of t he de nt ure cle a nser f oa m has bee n cli nicall y de m o nstra te d t o re m o ve de nt ure pla q ue 
(
) a n d d e nt ure stai n (
).  
T he m o de of acti o n is re p orte d t o be p h ysical, t hr o u g h br us hi n g, a u g me nt e d b y t he s urfacta nts 
prese nt i n t he f oa m.  
T he cli nical oral healt h efficac y of t he ra n ge of de ntal/ de nt ure pr o d ucts will be i n vesti gate d i n 
s u bjects wit h cli nicall y dia g n ose d mil d-m o derate gi n gi vitis.  
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 bjecti ves  
E n d p oi nts  
Pri m ar y  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s i n m ai nt ai ni n g g u m h e alt h b y r e d u ci n g gi n gi v al bl e e di n g 
(f oll o wi n g d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e Bl e e di n g I n d e x 
( BI), c o m p ar e d t o n o i nt er v e nti o n (e xi sti n g or al h y gi e n e) , w h e n u s e d 
t wi c e d ail y f or 1 2 w e e k s. 
BI at 1 2 w e e k s.  
S e c o n d ar y  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s  i n m ai nt ai ni n g g u m h e alt h b y r e d u ci n g gi n gi v al bl e e di n g 
(f oll o wi n g d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e n u m b er of 
bl e e di n g sit e s, c o m p ar e d t o n o i nt er v e nti o n ( e xi sti n g or al h y gi e n e) , 
w h e n u s e d t wi c e d ail y f or 6 a n d 1 2 w e e k s.  
N u m b er of bl e e di n g sit e s at 
6 a n d 1 2 w e e k s.  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s  i n m ai nt ai ni n g g u m h e alt h b y r e d u ci n g gi n gi v al 
i nfl a m m ati o n (f oll o wi n g d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e 
M o difi e d Gi n g i v al I n d e x ( M GI), c o m p ar e d t o n o i nt er v e nti o n (e xi sti n g 
or al h y gi e n e) , w h e n u s e d t wi c e d ail y f or 6 a n d 1 2 w e e k s. 
M GI at 6 a n d 1 2 w e e k s.  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s i n r e d u ci n g s u pr a-gi n gi v al pl a q u e f or m ati o n (f oll o wi n g 
d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e T ur e s k y Pl a q u e I n d e x 
( T PI), c o m p ar e d t o n o i nt er v e nti o n (e xi sti n g or al h y gi e n e) , w h e n 
u s e d t wi c e d ail y f or 6 a n d 1 2 w e e k s.  
T PI ( o v er all a n d 
i nt er pr o xi m al) at 6 a n d 1 2 
w e e k s.  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s  i n m ai nt ai ni n g g u m h e alt h b y r e d u ci n g gi n gi v al bl e e di n g 
(f oll o wi n g d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e Bl e e di n g I n d e x, 
c o m p ar e d t o n o i nt er v e nti o n ( e xi sti n g or al h y gi e n e) , w h e n u s e d 
t wi c e d ail y f or 6 w e e k s. 
BI at 6 w e e k s.  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s  i n m ai nt ai ni n g t h e cl e a nli n e s s of p arti al d e nt ur e s, a s 
m e a s ur e d b y t h e P arti al D e nt ur e Cl e a nli n e s s I n d e x ( P D CI), 
c o m p ar e d t o n o i nt er v e nti o n ( e xi sti n g or al h y gi e n e), w h e n u s e d 
t wi c e d ail y f or 6 a n d 1 2 w e e k s. 
P D CI s c or e s at 6 a n d 1 2 
w e e k s.  
T o e v al u at e t h e cli ni c al effi c a c y of a r a n g e of d e nt al/ d e nt ur e 
pr o d u ct s  i n r e d u ci n g s u pr a-gi n gi v al c al c ul u s f or m ati o n (f oll o wi n g 
d e nt al pr o p h yl a xi s), a s m e a s ur e d b y t h e c al c ul u s i n d e x 
( CI) c o m p o n e nt of t h e or al h y gi e n e i n d e x ( O HI), c o m p ar e d t o n o 
i nt er v e nti o n (e xi sti n g or al h y gi e n e) , w h e n u s e d t wi c e d ail y f or 6 a n d 
1 2 w e e k s.  
CI s c or e s at 6 a n d 1 2 w e e k s.  
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
C CI
C CI

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To evaluate the clinical efficacy of a range of dental/denture 
products in reducing oral debris (following dental prophylaxis), as 
measured by the oral debris index component of the OHI, compared 
to no intervention (existing oral hygiene), when used twice daily for 6 
and 12 weeks. 
ODI scores at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in improving oral hygiene (following dental prophylaxis), as 
measured by the OHI score (composite score of calculus and oral 
debris indices), compared to no intervention (existing oral hygiene), 
when used twice daily for 6 and 12 weeks. 
OHI scores at 6 and 12 
weeks. 
Exploratory 
To evaluate subject’s perceptions of dental/denture cleaning at 6 
and 12 weeks. 
Scores from Cleaning 
Perceptions Questionnaire at 
6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the Bleeding Index, compared to no 
intervention (existing oral hygiene), when used twice daily for 6 and 
12 weeks. 
BI associated with abutment 
teeth at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the number of bleeding sites, 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
Number of bleeding sites 
associated with abutment 
teeth at 6 and 12 weeks.  
To evaluate the clinical efficacy of a range of dental/denture 
products in maintaining gum health by reducing gum problems 
associated with denture abutment teeth (following dental 
prophylaxis), as measured by the Modified Gingival Index, 
compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
MGI associated with 
abutment teeth at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival plaque formation associated 
with denture abutment teeth (following dental prophylaxis), as 
measured by the modified Turesky Plaque Index, compared to no 
intervention (existing oral hygiene), when used twice daily for 6 and 
12 weeks. 
TPI associated with 
abutment teeth (overall and 
interproximal) at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing supra-gingival calculus formation associated 
with denture abutment teeth (following dental prophylaxis), as 
measured by the calculus index (CI) component of the oral hygiene 
index (OHI), compared to no intervention (existing oral hygiene), 
when used twice daily for 6 and 12 weeks. 
CI associated with abutment 
teeth at 6 and 12 weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in reducing oral debris associated with denture abutment 
teeth (following dental prophylaxis), as measured by the oral debris 
index component of the OHI, compared to no intervention (existing 
oral hygiene), when used twice daily for 6 and 12 weeks. 
ODI associated with 
abutment teeth at 6 and 12 
weeks. 
To evaluate the clinical efficacy of a range of dental/denture 
products in improving oral hygiene associated with denture 
abutment teeth (following dental prophylaxis), as measured by the 
OHI score (composite score of calculus and oral debris indices), 
OHI associated with 
abutment teeth at 6 and 12 
weeks. 
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compared to no intervention (existing oral hygiene), when used 
twice daily for 6 and 12 weeks. 
To capture photographic images of RPDs for each of the scores in 
the PDCI scale to assist study site staff with consistent evaluation of 
the PDCI over the duration of the study, to assist with future studies 
that might use this scale, and to aid to interpretation of results 
(including publication of the study outcomes). 
Photographs of RPDs. 
Safety 
To assess the safety and tolerability of a range of dental/denture 
products when used twice daily for 12 weeks. 
Treatment emergent adverse 
events and incidents. 
This study will be considered successful if a statistically significant improvement in BI, 
compared to the no intervention group (existing oral hygiene) at an alpha level of 0.05, is 
observed following 12 weeks twice daily use of a range of dental/denture products. 
4 
STUDY DESIGN  
4.1 
Overall Design 
This will be a single-center, single-blind (to the examiner(s) performing the plaque, denture 
cleanliness, oral hygiene and gingivitis assessments), randomized, stratified (by denture 
material type and baseline mean overall MGI score), two-treatment, parallel group, 12 week 
clinical study in generally healthy, adult volunteers with one conventional RPD and generalized, 
mild-moderate, plaque-induced gum problems (as determined by clinical examination) and ≥4 
natural teeth in each arch that meet all study criteria at both the Screening and Baseline visits 
(including ≥ 30 evaluable surfaces for clinical evaluation of gum problems and plaque).  The 
study will examine the effects of the use of a range of dental/denture products (comprising use 
of a dentifrice, a mouthrinse and a denture cleanser) compared to the use of no intervention 
(existing oral hygiene).  There will be four visits to the study site: Screening, Baseline, and after 
6 and 12 Weeks products use.  Gum problems will be assessed using the Modified Gingival 
Index (MGI) (Lobene, 1986) and a Bleeding Index (BI) (Saxton and Ouderaa, 1989).  Plaque 
will be assessed by the Turesky modification of the Quigley & Hein Plaque Index (TPI) (Lobene 
et al, 1982), oral hygiene by the Oral Hygiene Index (OHI) (Greene and Vermillion, 1960) and 
the cleanliness of the denture assessed using the Partial Denture Cleanliness Index (PDCI) 
(Blair et al, 1995).  Additionally, the subject’s perceptions to denture/dental cleanliness will be 
determined through a questionnaire. 
Sufficient subjects will be screened in order to randomize approximately 150 (maximum 175) 
to ensure approximately 128 evaluable subjects complete the entire study. 
Study subjects will be aged at least 18 years, in good general health, non-smokers (defined as 
not having smoked [including e-cigarettes] for the previous 12 months), with generalized, mild-
moderate, plaque-induced gingivitis (as determined by clinical examination) and ≥ 4 natural 
teeth in each arch that meet all study criteria at both the Screening and Baseline visits (including 
≥ 30 evaluable surfaces for MGI, BI, OHI and TPI) and who wear a single conventional acrylic 
or cobalt chrome RPD. 
At the Screening visit (Visit 1), subjects will give their written informed consent to participate 
in the study.  Demographics, medical history, dental history, current medications will be 
recorded, followed by an oral and RPD examination and a gingival assessment.  Screening 
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assessments will include full oral soft tissue (OST) and oral hard tissue (OHT) examinations 
(including dentition exclusions and gingival status), the fit of the RPD and whether it is well-
made.  Inclusion and Exclusion criteria as well as Subject eligibility will be assessed.  Subjects 
will be instructed to continue to brush using their usual dentifrice and following their usual 
dental/denture cleaning routine between screening and baseline. 
Within 1-28 days of Screening (Visit 1), eligible subjects will return to the site for the Baseline 
visit (Visit 2) with overnight plaque (subjects will abstain from any oral/denture hygiene for a 
minimum of 12 hours [maximum 18 hours] i.e. overnight, immediately before the visit).  
Subjects will have their medications recorded and will undergo, in the following order, 
completion of the questionnaire, removal of their denture with PDCI assessment, RPD 
photography (for a subset of subjects only in accordance with Section 8.2.5) then undergo a full 
OST examination and assessments of gingival inflammation (MGI followed by BI).  Following 
the MGI and CI assessments, and after rinsing with approximately 20ml of water, subjects will 
have their dental plaque disclosed before undergoing the TPI, ODI and BI assessments (in that 
order). 
Eligible subjects will continue in the study.  Subjects with a mean overall BI, MGI or TPI scores 
outside the study range will no longer be eligible to continue in the study and will be 
discontinued from the study at this visit.  To control inter-examiner variability, the same suitably 
qualified examiner will be used throughout the study for each of the dental assessments as far 
as possible.  The same examiner can perform more than one assessment, but as far as possible 
the same examiner must perform each of these assessments for all subjects throughout the study. 
Eligible subjects will be stratified based on denture material type (acrylic or cobalt chrome) and 
baseline mean overall MGI score (low: <2.0; high >2.0) to ensure a balance in treatments across 
the strata, and then randomized into one of two treatment groups.  A dental prophylaxis will be 
performed by a suitably qualified member of site staff for each eligible subject using a standard 
fluoride-free dental prophylaxis paste followed by flossing.  Subject’s teeth will be disclosed 
using a disclosing solution to check for residual plaque.  A second clinician will check to ensure 
all plaque has been removed.  Any residual plaque & calculus remaining will be removed by 
the second clinician by dental polishing with a standard fluoride-free dental prophylaxis paste, 
to bring the subject to a confirmed score of zero visible plaque (TPI=0).  The subject’s RPD 
will also be cleaned by a suitable qualified member of clinical staff using the supplied denture 
cleaning paste and brush so that there is no visible plaque and no matter adherent to the dental 
probe on light scraping (i.e. a PDCI score of 0). 
Following dental prophylaxis and RPD cleansing, subjects randomized to use of the range of 
dental/denture products will receive their assigned study products (including sundry items), a 
diary and instructions on product usage.  These subjects, under supervision, will brush their 
teeth with the dentifrice provided, in their usual manner for two timed minutes, clean their RPD 
with the supplied denture foam cleanser and brush in accordance with the product usage 
instructions and then rinse their mouths with the mouthrinse for 1 timed minute.  The subjects 
will then re-fit their RPD in their mouth.  Subjects will continue to use their supplied products 
twice per day, recording each use in their study diary.  Subjects randomized to the no 
intervention group will continue with their usual dental/denture cleansing habits.  All 
randomized subjects will receive general oral care advice and should record details of each of 
their tooth brushing/ mouth rinsing and denture cleansing activities in their study diary along 
with any new medications taken or change to their existing medication. 
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Subjects will return to the study site 6 and 12 weeks after randomization (Visits 3 and 4, 
respectively) having abstained from oral hygiene for a minimum of 12 hours (maximum of 18 
hours) i.e. from overnight, immediately before each assessment visit, if possible, at 
approximately the same time of day as the baseline visit.  The study products will be collected 
(from subjects randomized to the Interventional product range only), and these and the diary 
reviewed for treatment compliance.  Subjects randomized to the no intervention group will have 
their diary reviewed to ensure these subjects have continued with their usual oral hygiene.  
Subjects will complete the questionnaire, remove their denture which will be assessed using the 
PDCI.  They will then have a full OST examination and then undergo, in the following order, 
MGI, CI, plaque disclosure, TPI, ODI then BI assessments.  At Visit 3, subjects randomized to 
the interventional range of products will receive another supply of assigned study products and 
undergo supervised use of the study products per the usage instructions and all subjects will 
have their diary returned to them.  At Visit 4, subjects will return all study materials, undergo 
an OHT examination and have a dental prophylaxis and their denture cleaned if deemed 
appropriate by the investigator/examiner and/or requested by the subject.   
At Visits 2, 3, 4, repeatability data will be generated for MGI & TPI assessments from replicate 
examinations on the same subject.  Depending on subject visit scheduling, every effort will be 
made to complete one repeatability examination for each clinical measure during each clinical 
session, that is, at least one in the morning and at least one in the afternoon on each assessment 
day.  Repeatability examinations will be separated by a minimum of 10 minutes and, where 
possible, separated by another subject.   
All evaluable teeth (in relation to the inclusion/ exclusion general dentition criteria) will be 
assessed for MGI, CI, TPI, ODI and BI at baseline, 6 and 12 weeks. 
To aid study compliance, all subjects currently active in the study will receive an SMS (text 
message) reminder from the study site before a scheduled visit (Visits 2-4) to remind them of 
the requirement for no oral hygiene on the morning prior to their visit. 
4.2 
Rationale for Study Design 
The clinical design employed here is typical of many studies conducted to evaluate the clinical 
efficacy of oral healthcare products in the treatment of gum problems, albeit this design is 
generally employed in non-denture wearers.  Owing to the lack of clinical measures to probe 
oral health, gingivitis and plaque measurements (e.g. bleeding index, modified gingival index, 
Turesky plaque index) will be utilized in this study as markers of general oral health.  Study 
subjects with a pre-specified level of gum problems are randomized to either the intervention 
range of products group or a no intervention group; efficacy is determined after professional 
dental cleaning and a period of twice-daily brushing.  Dental prophylaxis removes all visible 
calculus and stain from the surface of the teeth (plaque retentive factors that could influence 
plaque accumulation) and ensures study subjects enter the treatment period with no visible 
plaque (TPI = 0).  This clinical study design has been chosen as this is recommended by the 
dental research communities and is consistent with American Dental Association (ADA) 
guidelines for such studies (ADA, 2016). 
A parallel group design has been selected as most appropriate for this investigation owing to 
the difficulties in ensuring an adequate latent period between study periods in a cross-over 
design. 
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Twelve weeks is deemed sufficient time to evaluate product effectiveness in this clinical design 
as demonstrated by numerous previous studies e.g. (Parkinson et al, 2018a; Parkinson et al, 
2018b) and as recommended by ADA guidelines (ADA, 2016). 
The application of twice daily tooth brushing, mouth rinsing and denture cleansing (morning 
and evening), the dose of the study products, method and duration of application are based on 
widely recommended oral hygiene practice, and typical consumer habits and is also in 
accordance with current or intended product labels.  To facilitate compliance with product usage 
throughout the study, and to enable staff to confirm correct dosing, a supervised brushing for 
subjects randomized to the intervention group will be performed on site at the end of Visits 2 
and 3; subjects will also be required to record each use of study product in the diary provided.  
Additionally, a timer will be provided to the subjects to aid compliance with the product usage 
instructions. 
The MGI and the BI are established clinical measures of gingival inflammation and gingival 
bleeding, respectively (i.e. gingival health); the TPI is an established clinical measure of supra-
gingival plaque accumulation.  The OHI is an established and well-used clinical measure of 
overall dental cleanliness.  To avoid inter-examiner variability, a single examiner will be 
responsible for the conduct of each clinical assessment for the duration of the study.  To assess 
examiner reproducibility across the treatment period, repeat MGI and TPI assessments will be 
performed on selected subjects at Visits 2-4.  Due to the invasive nature of the index, 
repeatability assessments are not feasible for the BI.  TPI and MGI are both recommended 
indices for the evaluation of plaque and gingivitis by the ADA (ADA, 2016).  Eligible subjects 
should have a mean whole mouth BI ≥ 0.1 to ≤ 1.3, a mean whole mouth MGI ≥ 1.75 to ≤ 2.30 
and a mean overall TPI score >1.5 at the Baseline visit.  These requirements are to ensure that 
appropriate subjects with mild-moderate gingivitis are recruited and are consistent with 
previous clinical studies of similar design (Parkinson et al, 2018a; Parkinson et al, 2018b) and 
follows FDA recommendation (FDA, 2005). 
Early stages of gum disease, prior to loss of tissue attachment, is considered to be an essentially 
reversible condition (Chapple et al, 2018) and the generally accepted treatment option for the 
dental practitioner is to administer an oral prophylaxis (Lamont et al, 2018), which, in this study, 
is administered to all subjects at Visit 2 (baseline) and offered to all subjects at the end of the 
study.  Therefore, assigning subjects with mild-moderate gingivitis to continued use of their 
existing oral hygiene is expected to result in improvement in their condition based upon the 
prophylaxis administered.  However, it would be inappropriate to recruit subjects with severe 
gingivitis/periodontitis into this study since these subjects should undergo immediate 
appropriate medical treatment.  A minimum of 4 teeth per arch is required in this study since it 
is considered a practical minimum number of teeth required to support an RPD adequately. 
According to the International Conference on Harmonisation (ICH) guidelines (ICH, Nov 2016), 
for a study to be classified as truly double-blind, not only does the examiner (and any 
appropriate member of staff who may be involved in the dispensing of products, analysis of 
data etc.) need to be blind to the treatment a subject receives, but the products under test must 
be identical in every way (color, flavor, rheology, appearance, packaging).  Given the subjects 
in the no intervention group will continue with their current oral hygiene practice and not be 
assigned any product to use, the level of blindness for this study is described as ‘examiner blind’ 
only.  The same examiner will be used for each clinical index throughout the study to eliminate 
the possibility of inter-examiner variability. 
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The effects of smoking on periodontal health are well documented in the scientific literature. 
Smoking decreases blood flow within the gingival microvasculature and interferes with 
neutrophil function, suppressing the inflammatory response to dental plaque and masking the 
clinical signs of periodontal disease (Kinane, 2001; Lie et al, 1998; Machuca et al, 2000; Obeid 
and Bercy, 2000; Shearer et al, 2005).  A 14-day experimental gingivitis model reported much 
less gingival bleeding in smokers compared to non-smokers, even though plaque levels and the 
composition of the oral microflora were similar between the two groups (Lie et al, 1998). 
Smokers (and tobacco users) will therefore be excluded from this investigation of product 
efficacy for the treatment of plaque-induced gingivitis.  The RPD wearers that are going to be 
recruited for this study should be subjects who do not frequently use denture cleansers (defined 
as those subjects who do not use marketed denture cleanser tablets or liquids more frequently 
than once per month).  These subjects form the largest group of the partial wearers, about 51% 
as shown in a GSK global segmentation study (GSK data on file) and thus will represent the 
behavior of the most typical partial denture wearer.  Subjects should not be taking medication 
which alters gingival appearance/bleeding and in accordance with ADA guidelines (ADA, 2016) 
their use within one month (28 days) prior to Baseline is prohibited. 
Gender is a known modifier of the initiation and outcome of conditions related to gingival health 
(Alam et al, 2012) and hormonal fluctuations through the female menstrual cycle may also 
influence response to dental plaque (Machuca et al, 1999; Raber‐Durlacher et al, 1994) and 
lead to increased variability in the clinical assessment of gingival health (Kovar et al, 1985).  In 
this study, both male and female subjects will be randomized to study product (in accordance 
with ADA guidelines (ADA, 2016)); gender will be included as a factor in the statistical analysis 
(Analysis of Covariance [ANCOVA]). 
Eligible subjects will be stratified according to their baseline mean overall MGI score (low: 
<2.0; high >2.0) and according to their denture type (acrylic or cobalt chrome) to ensure 
treatment groups are balanced.  Only subjects with an acrylic or cobalt/chrome RPD will be 
allowed in this study.  Whilst other materials (e.g. flexible nylon) can be used in the manufacture 
of RPDs, these are far less commonly utilised, and are therefore excluded from this study. 
Whilst the individual products being tested in this study are not contra-indicated for pregnancy 
and use of them would not be expected to cause harm either to the mother or foetus, pregnant 
females will be excluded from this study due to the increased prevalence and severity of 
gingivitis and periodontal disease along with increased amounts of calculus and plaque 
observed with pregnancy.  The severity of these conditions is known to vary during the course 
of pregnancy (Samant et al, 1976), and thus pregnancy would be a confounding factor of the 
objectives in this study.  Pregnant females and those intending to become pregnant are thus 
excluded in this study. 
In order for the clinical site to be able to remind subjects of the protocol requirements, subjects 
will be required to own a cell phone capable of receiving text messages. 
4.3 
Justification for Dose 
Use of the intervention range of products under investigation will involve subjects removing 
their RPD, brushing their natural teeth with the dentifrice, brushing their denture with the 
supplied denture foam then rinsing their mouth with a mouthrinse.  This will be performed twice 
daily (morning and evening).  
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The application of twice daily brushing, with a brush length of dentifrice is based on consumer 
habit and common practice within oral care clinical trials.  Subjects will apply a full ribbon of 
dentifrice to the study toothbrush and brush their teeth in their usual manner for two timed 
minutes twice daily (morning and evening).  Two minutes is chosen as the brushing time since 
this is the length of time typically advocated by dental professionals (NHS, 2019).  The denture 
cleanser will be applied to the RPD external to the mouth and brushed for 90s prior to thorough 
rinsing under running tap water twice-daily.  The mouthrinse dose is typical (10ml) and will be 
swished in the mouth twice daily for 1 minute after toothbrushing.  This aligns with common 
practice and the FDA anti-caries monograph (FDA, 1995).  The dosing of the range of products 
is in agreement with the proposed product labelling (for the dentifrice and mouthrinse) and the 
current product labelling (for the denture cleanser foam). 
Subjects in the non-intervention group will continue with their existing oral hygiene practices.  
This has been chosen as the relevant control for this study since the study objectives are to 
evaluate the improvement in overall oral hygiene through use of the interventional range of 
products and therefore comparing to a group that continues with their existing oral hygiene 
practice is appropriate. 
No dose modification is permitted in this study.  Any variation from the product usage 
instructions should be communicated to study site personnel and recorded as a deviation on the 
CRF. 
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 
(last subject last visit date). 
The end of this study is defined as the date of the last subject last visit date. 
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
This study will recruit healthy volunteers of either gender aged 18 years or older with mild-
moderate plaque-induced gingivitis who wear one removable partial denture.  The individual 
products used by subjects in the intervention group, when marketed, will be indicated for the 
general population who wear removable partial dentures and who are therefore at risk of further 
tooth loss.  The inclusion criteria allows for investigation of subjects typical to the indicated 
population. 
Sufficient subjects will be screened to randomize at least 150 (maximum 175) subjects (equally 
distributed across the two treatment groups) to ensure approximately 128 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, 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 
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considered appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether a subject is suitable for this protocol.   
5.2 
Inclusion Criteria 
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study. 
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 and 75 
years, inclusive. 
3. A subject who is willing and able to comply with scheduled visits, treatment plan, and 
other study procedures.  
4. A subject with good general and mental health with, in the opinion of the investigator or 
medically qualified designee no clinically significant or relevant abnormalities in medical 
history or upon oral examination, or a condition, that would impact the subject’s safety, 
wellbeing or the outcome of the study, if they were to participate in the study. 
5. A subject who is a cell phone owner with text messaging capabilities. 
6. Dental Criteria: 
a. A subject with a minimum of 4 natural teeth in each arch. 
b. A subject with a minimum of 30 scorable surfaces for MGI, BI, OHI and TPI. 
(A scorable surface is defined as a surface that has at least 2/3 of the surface gradable 
for each clinical index. Third molars, orthodontically banded/bonded, fully crowned 
or extensively restored or grossly carious teeth are not included in the tooth or 
scorable surface count.  Third molars can be included if, as a result tooth loss, they 
are functioning as second molars.  Tooth surfaces with calculus deposits which, in the 
opinion of the clinical examiner, would interfere with the assessments of the selected 
clinical indices are also excluded.) 
c. A subject with a minimum of 2 scorable abutment teeth, defined as teeth proximal to 
the RPD or impinged by an RPD clasp or rest. 
d. A subject with generalized mild-moderate plaque-induced gingivitis present at the 
screening visit (in the opinion of the clinical examiner from a gross visual 
examination).  
e. A subject with a mean whole mouth BI ≥ 0.1 to ≤ 1.3, a mean whole mouth MGI ≥ 
1.75 to ≤ 2.30 and a mean overall TPI score >1.5 at the Baseline visit. 
f. A subject who habitually wears one conventional removable partial denture 
constructed of acrylic or cobalt chrome which is acceptable according to the well-
made and well-fit assessments. 
5.3 
Exclusion Criteria 
A subject with any of the following characteristics/conditions will not be included in the study: 
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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 GSK CH 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 an acute or chronic medical or psychiatric condition that may increase the 
risk associated with study participation or investigational product administration or may 
interfere with the interpretation of study results and, in the judgment of the investigator, 
would make the subject inappropriate for entry into this study. 
4. A subject who is pregnant (self-reported) or intending to become pregnant over the 
duration of the study. 
5. A subject who is breastfeeding. 
6. A subject with known or suspected intolerance or hypersensitivity to the study materials 
(or closely related compounds) or any of their stated ingredients.  
7. A subject who smokes (defined as having smoked or used nicotine products (including e-
cigarettes, chewing tobacco, gutkha, pan-containing tobacco, nicotine replacement 
therapies) during the previous 12 months). 
8. A subject who is unwilling or unable to comply with the Lifestyle guidelines described in 
this protocol. 
9. A subject with a recent history (within the last year) of alcohol or other substance (e.g. 
illicit drug) abuse. 
10. A subject who has previously been enrolled in this study. 
11. A subject who, in the opinion of the investigator, should not participate in the study. 
12. Medication Exclusions: 
a. A subject who has taken or is currently taking antibiotics at the Screening visit or in 
the 14-day period prior to the Baseline visit or requiring antibiotic use prior to dental 
prophylaxis or other dental procedure. 
b. A subject who is currently taking, on a regular daily basis, an anti-inflammatory, anti-
coagulant or any other systemic medication (e.g. calcium channel blockers, aspirin 
therapy, ibuprofen, warfarin) or has a medical condition which, in the opinion of the 
Investigator, could affect the gingival condition. 
c. A subject who has used an antibacterial mouth rinse (e.g. chlorhexidine, Listerine), 
dentifrice (e.g. stannous fluoride) or use of any oral care product that, in the opinion 
of the investigator, could interfere with plaque accumulation or clinical measures 
within 28 days preceding the baseline visit. 
13. Oral and Dental Exclusions 
a. A subject with a condition or who is taking medication which, in the opinion of the 
investigator is causing xerostomia. 
b. A subject who, in the opinion of the investigator, has a periodontal condition that 
could be adversely affected by lack of immediate periodontal intervention. 
c. A subject who has received treatment for periodontal disease within 12 months of 
Screening and/or scaling or root surface debridement within 3 months of Screening, 
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which, in the opinion of the Investigator, could compromise study outcomes or the 
oral health of the subject if they were to participate in the study. 
d. A subject who has numerous restorations in a poor state of repair. 
e. A subject with a severe oral condition (e.g. acute necrotizing ulcerative gingivitis, 
severe 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. 
f. A subject who has had tooth bleaching treatment or a dental prophylaxis within 4 
weeks of screening. 
g. A subject who frequently use commercially-available denture cleansers, e.g. denture 
cleanser tablets, denture cleaning pastes (defined as those subjects who use a 
commercially available cleanser more frequently than once per month).  
h. A subject who currently use denture adhesives (defined as those subjects who have 
used an adhesive in the 28 day period prior to baseline). 
i. A subject who displays evidence of dental fluorosis that might interfere with clinical 
assessments, as determined by the investigator. 
j. A subject with gingivitis which, in the opinion of the investigator, is not expected to 
respond to treatment with an over-the-counter dentifrice. 
k. A subject who has an overdenture or orthodontic appliance. 
5.4 
Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.  Eligible subjects will be stratified based on denture material type (acrylic or cobalt 
chrome) and baseline mean overall MGI score (low: <2.0; high >2.0) to ensure a balance in 
treatments across the strata, and then randomized into one of two treatment groups (intervention 
/no intervention). 
There will be four strata according to denture material type (acrylic or cobalt/chrome) and 
baseline mean overall MGI score (Low≤2.0/High>2.0): 
• Stratum 1: Denture material is acrylic, Baseline MGI <2.0 
• Stratum 2: Denture material is acrylic, Baseline MGI >2.0 
• Stratum 3: Denture material is cobalt chrome, Baseline MGI <2.0 
• Stratum 4: Denture material is cobalt chrome, Baseline MGI >2.0 
Subjects will be allocated to one of the 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 
During the entire study (screening – subject’s last study visit): 
• Subjects will abstain from chewing gum and consuming confectionery containing xylitol 
(e.g. mints).  
• Subjects should abstain from interproximal cleaning (use of dental floss, waterpick and 
toothpicks).  Use of toothpicks is permitted to remove impacted food only. 
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• Subjects will abstain from use of antimicrobial mouthrinses or dentifrices and any over-
the-counter dental whiteners during the course of the study except those products supplied. 
• Subjects will be requested to not have any elective dental /denture procedures (including 
dental prophylaxis and tooth whitening) other than those performed within the study 
(excluding emergency dental treatment). 
• Subjects randomized to the intervention group should only use the dentifrice, mouth rinse, 
denture cleanser and toothbrushes provided and must abstain from use of all other oral 
hygiene products from the baseline visit.  They should abstain from interproximal cleaning 
(as defined above). 
• Subjects randomized to the no intervention group will be instructed to continue with their 
current dental/denture cleaning habits at baseline (excluding interproximal cleaning as 
defined above).  These subjects should endeavor to maintain their current oral/denture 
hygiene practice and not introduce any change throughout the entire study.  Any changes 
to a subject’s oral hygiene practices/products used that, in the opinion of the investigator 
or designee, are significant and consistent should be documented in the CRF as deviations. 
5.5.2 
Prior to Visits 2, 3 and 4: 
• Subjects must abstain from undergoing any oral hygiene (including denture cleansing) for 
a minimum of 12 hours (maximum of 18 hours) i.e. overnight immediately before an 
assessment visit (Visits 2, 3 and 4) until the visit is complete. 
• Subjects must abstain from eating for at least 4 hours, and from drinking for at least 1 hour 
prior to all clinical assessments and until all assessments are complete.  Small sips of 
water to aid in the taking of permitted medications and to relieve thirst are allowable. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized in the study. 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 
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Protocol Number: 212401 
 
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SP1963/SOP-208661: Template Version: 14 Mar 2019 
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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.   
5.8 
Rater/Clinical Assessor Qualifications 
The assessor(s) performing the MGI, TPI and BI, OST, OHT, PDCI, OHI well-made and well-
fit assessments and who perform the dental prophylaxis will be a suitably qualified dental 
professional.  The assessor(s) performing the MGI, TPI and BI assessments should have a 
demonstrable history of use of these indices in clinical trials.  The assessor(s) performing the 
well-made and well-fit assessments will have expert knowledge of prosthodontics. 
6 
INVESTIGATIONAL/STUDY PRODUCTS 
For the purposes of this study, per International Conference on Harmonization (ICH) guidelines, 
and GSK policy, investigational product is defined as a pharmaceutical form of an active 
ingredient, a non-medicinal product (marketed or investigational), or a placebo, being tested or 
used as a reference (positive or negative control), in a clinical trial.  This includes a product 
with a marketing authorization when used or assembled (formulated or packaged) in a way 
different from the approved form, or when used for an unapproved indication, or when used to 
gain further information about an approved use.  
6.1 
Investigational/Study Product Supplies 
The following study products will be supplied by the Clinical Supplies Department, GSK CH: 
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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 1 2 4 0 1 
 
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 K C 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 0  of 8 2  
 
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 
 
I nter ve nti o n Gr o u p 
N o I nter ve nti o n 
Gr o u p  
Pr o d uct Descri pti o n  
Ra n ge of De nt al/ De nt ure Pr o d ucts  
N/ A  
S u bjects will 
c o nti n ue wit h 
t heir e xisti n g oral 
h y gie ne  
Pr o d uct N a mes 
( F o r m ul ati o n 
C o des)  
E x peri me ntal De ntifrice c o ntai ni n g 0. 4 5 4 % 
sta n n o us fl u ori de ( 
) 
C O R E G A P urfrisc h Rei ni g u n gssc ha u m 
De nt ure F oa mi n g Clea ns er –  Ger ma n 
Mar ket place ( 
)  
E x peri me ntal M o ut hri nse c o ntai ni n g 9 0 p p m 
s o di u m fl u ori de ( 
) 
N/ A  
D ose  
A stri p of de ntifrice (f ull br us h hea d) br us he d 
f or 2 ti me d mi n utes, 2 p u m ps of de nt ure 
clea nser f oa m br us h e d o nt o R P D f or 9 0 ti me d 
sec o n ds a n d 1 0 ml of m o ut hri nse f or s wis he d 
ar o u n d t he m o ut h f or 1 ti m e d mi n ute.  
N/ A  
R o ute of 
A d mi nistr ati o n  
De ntifrice a n d m o ut hri nse a p plie d t o picall y 
orall y.  De nt ure clea ns er a p plie d t o de nt ure 
e xter nal t o t he m o ut h pri or t o ri nse off.  
N/ A  
D osi n g I nstr ucti o ns  
As per t he Pr o d uct Us a ge I nstr u ct i o ns 
N/ A  
 
T he d ose a n d fre q u e nc y (t wice p er d a y, m or ni n g a n d e v e ni n g) of a p plicati o n of t he i n di vi d ual 
pr o d ucts i n t he i nter ve nti o nal gr o u p is c o nsiste nt wit h la bel i nstr ucti o ns  ( de nt ure clea ns er f oa m), 
t he i nte n de d la bel i nstr ucti o ns ( de ntifrice a n d m o uthri nse) a n d t he te ntati ve F D A a nti -gi n gi vitis 
m o n o gra p h (F D A, 2 0 0 3 ) f or t h e de ntifri ce a n d t h e a nti-caries m o n o gra p h f or t he m o ut hri nse 
(F D A, 1 9 9 5 ). 
S u bjects ra n d o mize d t o t he n o i nter ve nti o n gr o u p will n ot be s u p plie d a n y pr o d ucts a n d will 
c o nti n ue wit h t heir e xisti n g de ntal/ de nt ure h y gie ne practices a n d s h o ul d e n dea v or n ot ma ke 
c ha n ges t o eit her t h eir est a blis he d ha bits n or t o t he pr o d ucts t he y use f oll o wi n g scree ni n g. A n y 
c ha n ges t o t heir oral h y gi e ne practices s h o ul d be rec or de d b y t he partici pa nt i n t heir diar y car d, 
a n d t h ose dee me d si g nifica nt a n d c o nsiste nt b y t he i n vesti gat or or t heir desi g ne e s h o ul d be 
detaile d i n t he C R F as de viati o ns.  
T he S u n dr y Ite ms t o be s u p plie d are det aile d i n Ta ble 6 -2 . 
T a bl e 6 -2  
S u n dr y It e m s  
Ite m 
S u p plie d 
B y  
P ac k 
Desi g n  
Dis pe nsi n g Det ails  
Ret ur n/ Dis p os al 
Det ails  
Use d 
S a m ples  
U n use d 
S a m ples  
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
C CI
C CI
C CI

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Wisdom 
Denture 
Brush 
GSK CH Commercial 
packaging 
To clean dentures (for use 
at the study site and by the 
subjects randomized to the 
intervention range of 
products to clean dentures 
at home). 
Destroyed 
at site 
according 
to site 
disposal 
procedures.  
Return 
Countdown 
Timer 
GSK CH 
Individual 
commercial 
pack – 1 per 
subject 
To accurately measure 
toothbrushing, mouth 
rinsing and denture 
cleansing activities.  To be 
used by subjects 
randomized to the 
intervention range of 
products only. 
Subject to 
keep or 
destroyed 
at site 
using site 
disposal 
procedures. 
Return 
Dentu 
Creme 
Denture 
cleansing 
paste  
GSK CH 
Individual 
commercial 
pack 
To clean dentures at the 
study site only by the 
dental professional 
Return. 
Return 
Aquafresh 
Clean 
Control 
toothbrushes 
GSK CH 
Individual 
commercial 
pack – 2 per 
subject 
To apply dentifrice to the 
teeth and facilitate 
toothbrushing.  To be used 
by subjects randomized to 
the intervention range of 
products only. 
Destroyed 
at site 
according 
to site 
disposal 
procedures.  
Return 
Dosing cups GSK CH N/A 
For dosing of mouthrinse.  
To be used by subjects 
randomized to the 
intervention range of 
products only. 
Destroyed 
at site 
following 
site 
procedures.  
Return 
Trace plaque 
disclosing 
solution 
GSK CH 
Individual 
commercial 
pack 
To disclose the presence of 
dental plaque at the study 
site only 
To be 
destroyed 
at site 
according 
to site 
procedures. 
Return 
Detailed instructions for the return 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 dentifrice will be supplied in individual tubes.  The experimental mouthrinse 
will be supplied in individual bottles.  The denture foam will be supplied in individual 
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dispensers with the commercial labels either removed or overwrapped to hide the identity of 
the product. 
The content of the product labels will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the GSK CH Global Clinical Supplies group. 
Each study label will contain, but not be limited to, protocol number, directions for use and 
storage requirements.  
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 
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 the clinical site staff 
should ensure the dispensing procedures are completed accurately.  Initial dispensing of study 
products should occur at Visit 2 with additional re-dispensing at Visit 3.  The dispensing should 
be performed in a room away from other subjects and blinded study staff (especially the 
examiner performing the efficacy and safety assessments, who will be prevented from viewing 
subjects once they have their study products).  The study site will be provided with opaque bags 
in which the study products, diaries and product usage instructions will be placed in the bag 
prior to the subject leaving the dispensing area.  Subjects randomized to the no intervention 
group will have just their diaries in the opaque bag. 
Subjects should be advised as to correct product usage in accordance with the Product Usage 
Instructions at each visit.  All randomized subjects should receive standard oral care advice at 
Visit 2 (section 8.2.1).   
6.2 
Administration 
Subjects randomized to the intervention group will undertake first usage of the range of 
dental/denture products under supervision at the clinical site.  These subjects will be instructed 
to self-administer their assigned range of products twice per day (morning and evening) per the 
Product Usage Instructions provided to the subject and will use their products under supervision 
again at Visit 3 to ensure adherence to the 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, 
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• 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 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. 
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. 
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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. 
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. 
All unused product should be returned to the study site by the subjects at each visit. 
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. Please see table of sundry items for return or destruction details.  
Detailed instructions for the return 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. 
6.5 
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. 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. 
The investigator’s knowledge of the product allocation should not influence the decision to 
enroll a subject or affect the order in which subjects are enrolled. 
This study is described as single-blind (to the examiner(s) performing the plaque and gingivitis 
assessments). 
To ensure the examiner remains blinded throughout the study, staff involved in the 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.  Subjects randomized to the interventional group 
will have the study products, sundry items and their diary and usage instructions contained 
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within the bag, whilst the subjects randomized to the no intervention group will have their diary 
in the bag. 
Dispensing staff will not be involved in any efficacy/safety assessment procedures during the 
study. 
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. 
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 or incident associated with breaking the blind must be recorded and reported as 
specified in this protocol. The study site may also be required to inform the Institutional Review 
Board / Ethics Committee (IRB/EC) if the blind is broken.  
6.7 
Compliance 
A diary will be supplied to promote compliance and to capture details of product use throughout 
the study period.  Subjects randomized to the no intervention group should record their 
dental/denture cleansing events in the diary.  All subjects should also record, in the diary, 
additional information such as AEs or changes in medications used.  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.  Additionally, all subjects 
currently active in the study will receive an SMS (text message) reminder from the study site 
prior to a scheduled visit (Visits 2-4) to remind them of the requirement for no oral hygiene on 
the morning prior to their visit. 
During study site visits (Visits 2&3) subjects randomised to use of the interventional range of 
products will have correct product usage demonstrated to them by the study site staff.  Subjects 
will then undergo supervised product usage which will be witnessed by the study site staff and 
incorrect application will be corrected. 
Subjects randomised to the interventional range of products will be supplied with a dosing cup 
to ensure accurate dosing of the mouthrinse.  These subjects will also be asked to bring their 
assigned study products at each visit, so that the compliance assessments can be made based 
upon observation of the amount of product used and so they can undergo supervised product 
application at Visit 3. 
The number of any missed or additional applications or doses for subjects in the intervention 
group 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. 
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For subjects in the non-intervention group, changes to their oral hygiene behavior compared to 
their behavior as recorded at screening which are deemed significant and consistent by the 
investigator or their designee will be captured as protocol deviations in the CRF. 
Subjects randomized to use of the interventional range of products will be instructed 
in/reminded of the correct usage of the product at visits 2 and 3 by the dispensing staff with 
subsequent supervised product usage at these visits. 
Failure of any subject to follow the oral care advice given at Visit 2 (see section 8.2.1) will not 
be considered as a deviation except where this failure is covered by other inclusion/exclusion 
criteria, lifestyle considerations or product usage instructions detailed within this protocol. 
6.8 
Concomitant Medication/Treatment(s) 
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. 
Details of any relevant dental, medical or surgical history (within the last year), including 
allergies or drug sensitivity, will be recorded in the CRF.  The use of concomitant medications 
is permitted in this study except for the use of anti-biotics, anti-inflammatory or anti-coagulants 
drugs as per the exclusion criteria, and any medications that in the opinion of the investigator 
would interfere with the conduct of this study per the inclusion/ exclusion criteria.  Occasional 
use of anti-inflammatory drugs (e.g. ibuprofen) is allowable, if in the opinion of the investigator, 
the use would not affect the gingival condition. 
Medication/treatments taken within 28 days of signing the informed consent form will be 
documented as a prior medication/treatment.  Medications/treatments taken on and after Visit 
2 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 
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 
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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 and subject’s consent, which could include an OST and OHT 
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. 
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 
Visit 1/Screening 
Screening procedures will be conducted by the Investigator, or suitably qualified designee. 
Subjects will be screened within 1-28 days prior to randomization to confirm that they meet the 
subject selection criteria for the study.   
The following Screening procedures will be completed, in the following order (wherever 
possible), and the findings recorded in the CRF: 
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1. Informed Consent 
2. Demographics 
3. Review of medical history (including smoking/tobacco use status) and prior 
medication/treatment  
4. Review of current/concomitant medication 
5. Review of dental history 
6. Well-fit assessment of the RPD 
7. Subject removes RPD 
8. Well-made assessment of the RPD 
9. Full OST and OHT examinations 
10. Gross gingival assessment 
11. Review of the inclusion/exclusion criteria 
12. Subject eligibility 
13. RPD is returned to subject 
14. AEs and Incidents recorded 
8.1.1 
Screening Procedures 
8.1.1.1 
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. 
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8.1.1.2 
Demographics 
The following demographic information will be recorded in the CRF: year of birth, gender and 
race.  Ethnicity and race of subjects will be recorded in accordance with FDA Guidance for 
Industry: Collection of Race and Ethnicity Data in Clinical Trials, 2005. 
8.1.1.3 
Medical History and Prior Medication/Treatment 
Details of relevant medical and surgical history (in the last year), including allergies or drug 
sensitivity, will be documented in the CRF. 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 28 days and prior to signing the informed 
consent form, will be documented in the CRF. 
The smoking/tobacco usage status of the subject should be recorded. 
8.1.1.4 
Dental History 
The dental history of the subjects should be taken.  Examples of the questions that should be 
solicited are given in Appendix 15.3. 
8.1.1.5 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information will be documented in the CRF.  The OST, OHT, 
gross gingival assessment, well-made and well-fit assessments should be performed by suitably 
qualified examiners as described in Section 5.8. 
8.1.1.6 
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. 
8.2 
Study Period 
8.2.1 
Visit 2/Day 0 – Baseline 
Procedures will be conducted by the Investigator, or suitably qualified designee. 
Subjects will undergo, in the following order (wherever possible), and findings documented in 
the CRF: 
1. Changes in health, medication and non-drug treatments/procedures will be documented in 
the CRF. 
2. 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. 
3. Subject completes the questionnaire. 
4. Subject removes RPD. 
5. RPD is assessed for PDCI. 
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6. For a subset of subjects, photographic images of their RPD will be taken. 
7. Subject undergoes a full OST examination. 
8. Subject undergoes MGI assessment including a repeat assessment if required. 
9. Subject undergoes a CI assessment. 
10. Subject undergoes plaque disclosure and TPI including a repeat assessment if required. 
11. Subject undergoes ODI assessment. 
12. Subject undergoes BI assessment. 
13. Review of the inclusion/exclusion criteria. 
14. Subject eligibility assessed. 
15. Subjects will be stratified and randomized to treatment group. 
16. Subject’s RPD will be cleaned by the study site and the subject will undergo a full sub and 
supra-gingival prophylaxis with confirmation of a TPI score of zero by a second suitably 
qualified member of site staff. 
17. The subject’s RPD will be returned. 
18. Intervention group only - study products will be dispensed, including sundry items, 
product usage instructions and diary.  Subject to perform supervised product usage and 
study staff to review instructions on correct product use with the subject for at home use. 
19. No intervention group only – subject to receive only the diary. 
20. All randomized subjects will receive standard oral care advice to brush their teeth twice 
per day with a fluoridated toothpaste, to remove their partial denture while sleeping, to 
clean their denture and to visit their dentist regularly. 
21. AEs and incidents recorded. 
8.2.2 
Visit 3/Day 42 ±3  
Procedures will be conducted by the Investigator, or suitably qualified designee. 
Subjects will undergo, in the following order (wherever possible), and findings documented in 
the CRF: 
1. Changes in health, medication and non-drug treatments/procedures will be documented in 
the CRF. 
2. 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. 
3. Study products and diaries collected from subjects.  Staff will complete visual checks of 
the returned lead-in toothbrush/toothpaste and review the completed diary. Any suspected 
over or under use and the number of any missed or additional product usage will be 
documented in the CRF. 
4. Subjects compliance with treatment and denture cleaning assessed through examination of 
subject diary and product usage. 
5. Subject completes the questionnaire. 
6. Subject removes RPD. 
7. RPD is assessed for PDCI. 
8. For a subset of subjects an image(s) of their RPD will be taken.  This is only to be 
performed at this visit should insufficient images of acceptable quality not have been 
obtained at Visit 2. 
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9. Subject undergoes a full OST examination. 
10. Subject continuance assessed. 
11. Subject undergoes MGI assessment including a repeat assessment if required. 
12. Subject undergoes CI assessment. 
13. Subject undergoes plaque disclosure and TPI assessment including a repeat assessment if 
required. 
14. Subject undergoes ODI assessment. 
15. Subject undergoes BI assessment. 
16. The subject’s RPD will be returned. 
17. Intervention group only - study products will be dispensed, including sundry items, 
product usage instructions and their diary returned to subject.  Subject to perform 
supervised product usage and study staff to review instructions on correct product use with 
the subject for at home use. 
18. No intervention group only – subject to receive only their returned diary. 
19. AEs and incidents recorded. 
8.2.3 
Visit 4 /Day 84 ±3 
Procedures will be conducted by the Investigator, or suitably qualified designee. 
Subjects will undergo, in the following order (wherever possible), and findings documented in 
the CRF: 
1. Changes in health, medication and non-drug treatments/procedures will be documented in 
the CRF. 
2. 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. 
3. Study products and diaries collected from subjects. 
4. Subjects compliance to treatment and denture cleaning assessed through examination of 
subject diary and product usage. 
5. Subject completes the questionnaire. 
6. Subject removes RPD. 
7. RPD is assessed for PDCI. 
8. For a subset of samples an image(s) of their RPD will be taken.  This is only to be 
performed at this visit should insufficient images of acceptable quality not have been 
obtained at Visit 2/3. 
9. Subject undergoes a full OST examination. 
10. Subject undergoes a full OHT examination. 
11. Subject continuance assessed. 
12. Subject undergoes MGI assessment including a repeat assessment if required. 
13. Subject undergoes CI assessment. 
14. Subject undergoes plaque disclosure and TPI assessment including a repeat assessment if 
required. 
15. Subject undergoes ODI assessment. 
16. Subject undergoes BI assessment. 
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17. Subject undergoes an optional dental prophylaxis and RPD cleanse. 
18. The subject’s RPD will be returned 
19. AEs and incidents recorded. 
20. Study conclusion. 
8.2.4 
Study Procedures 
8.2.4.1 
Diary Review 
The diary should be reviewed for treatment compliance at every visit by the investigator, or 
suitably qualified designee. Any subject comment captured in the diary which is considered an 
adverse event will be assessed and reported as per the defined procedure in this protocol. 
Adverse event reporting procedures are summarized in Section 10. 
Any comments relating to medications/treatments provided in the diary will be reviewed by the 
investigator or medically qualified designee with the subject prior to the subject leaving the site 
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. 
The number of toothbrushing, mouthrinsing and denture cleaning occasions for all subjects 
since their previous visit should be recorded in the CRF. 
8.2.5 
Photography of RPD – subset of subjects only 
At Visit 2-4, photographs of the RPDs from a subset of subjects (chosen at the examiner’s 
discretion) are to be taken to demonstrate the range of scores of the PDCI.  The photographs 
are to assist study site staff with consistent evaluation of the PDCI over the duration of the 
study, to assist with future studies that might use this scale, and to aid interpretation of results 
(including publication/dissemination of the study outcomes). 
Extra oral digital photographs will be taken of the occlusal, fit and side views of each RPD 
immediately after the PDCI assessment.  No plaque disclosing agent should be used.   
This procedure should be performed by appropriately trained/experienced staff.  It is expected 
that approximately 3 separate RPDs be photographed per score of the PDCI index (0-4) 
wherever possible.  RPDs for photography should be chosen at the examiner’s discretion with 
the aim of ensuring clear photographs demonstrating the visual state of the RPD for each scale 
score of the PDCI.  For the zero PDCI score only it is acceptable to photograph RPDs that have 
undergone the denture cleansing procedure at Visit 2 (i.e. the photographs will be obtained 
immediately prior to return of the RPD to the subject).  It is expected that sufficient numbers of 
photographs will be obtained at Visit 2, however should insufficient photographs for all scores 
be taken at this visit (e.g. insufficient RPDs available that demonstrate a specific score) then it 
is acceptable to take additional photographs at Visits 3 and 4.  Photographs may be obtained 
from subjects randomized to either treatment groups.  It is accepted that there may be 
insufficient RPDs available for each of the PDCI scores. 
Photographs will be obtained using a digital camera with sufficient resolution and adequate 
lighting to convey the denture cleanliness.  Photographs should be taken with a black 
background and the image should contain a prominent numeral depicting the PDCI score at the 
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periphery of the photograph.  Images should be obtained as soon as possible after the PDCI 
grading. 
Digital photographs and their filenames will not contain any personally identifiable information. 
The digital file should be appropriately named to identify the subject screening number and the 
associated PDCI score.  The only photographs that will be taken will be of dentures outside of 
the mouth.  No images of subjects will be obtained.  No analysis of any kind will be performed 
on these images. 
8.2.6 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information will be documented in the CRF.  The MGI, TPI, 
CI, ODI, BI, OST, OHT and PDCI assessments and the prophylaxis should be performed by 
suitably qualified examiners as described in Section 5.8. 
8.2.7 
Supervised Product Application 
Subjects randomized to the interventional group will be instructed on how to use the study 
products at Visits 2&3.  Written product usage instructions will also be provided, and these 
should be read by the subject immediately prior to undergoing supervised use of the products.  
A member of the study site staff should observe this supervised application and advise/correct 
any incorrect product usage. 
8.2.8 
Dental Prophylaxis and RPD Cleansing 
A suitably qualified member of clinical staff will provide professional dental prophylaxis for 
each subject using a standard prophylaxis polishing paste followed by flossing to ensure teeth 
are free of all supra and gingival calculus and plaque, both visually and by tactile assessment 
using a dental explorer.  A second suitably qualified examiner will then visually check that all 
plaque has been removed following plaque disclosure.  Subjects will have their plaque disclosed 
and any residual plaque remaining will be removed by the second clinician by dental polishing 
with a standard prophylaxis polishing paste to bring the subject to zero plaque (TPI=0). 
Each RPD will be cleaned by a suitably qualified member of the clinical staff to zero plaque 
state, assessed by visual examination, by using the supplied denture brush and denture cleansing 
paste followed by rinsing thoroughly with tap water before returning to the subject.  No 
disclosing agent will be used whilst cleaning the RPD. 
In addition, at the final study visit, subjects will be offered a dental prophylaxis and RPD 
cleaning by a suitably qualified member of the clinical staff if determined appropriate in the 
opinion of the investigator or suitably clinically qualified designee. 
8.2.9 
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, AEs or incidents at the 
end of the study, the GSK CH medical monitor (or designated representative) should be notified 
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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.  
8.2.10 
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, 
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. 
9.1.1 
OST Examination 
The screening clinician will perform an initial oral soft tissue examination in agreement with 
Section 9.3.1 in order to record any abnormalities and assess the subject’s eligibility for 
enrollment into the study. 
9.1.2 
OHT Examination 
The screening clinician will perform a visual examination of the oral hard tissues in agreement 
with Section 9.3.2 in order to record any abnormalities and assess the subject’s eligibility for 
enrollment into the study. 
9.1.3 
Gross Gingival Health Assessment 
The screening dentist will determine gingival health by visual examination of the subject’s oral 
soft tissue.  Subjects considered to have generalized mild-moderate gingivitis will continue in 
the study. 
9.1.4 
Evaluation of Well Fit Partial Denture 
The clinical assessment of denture fit will be made by an examiner with expert knowledge of 
removable prosthodontics.  Higher values indicate a more favorable prosthesis. 
Retention Criteria 
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0= Inadequate retention that cannot be adjusted.  Prosthesis displaces and rocks when 
torque forces are applied. 
1=Inadequate retention that can be adjusted by laboratory clasp adjustment. 
2=Retention is adequate but there is slight displacement when torque forces are applied.  
It can be adjusted. 
3=Retention is adequate and does not displace when torque forces are applied. 
Stability Criteria 
0=Poor stability due to inadequate saddle area extension and appliance fit that cannot 
be adjusted. 
1=Partial denture is not stable due to inadequate saddle area that can be corrected by 
laboratory reline. 
2=Partial denture is slightly unstable but can be adjusted. 
3=Saddle area is properly covered, and partial denture has adequate stability. 
Fit and Function 
0=Prosthesis has poor fit and causes tissue irritation.  Occlusion is worn out and 
appliance induces tooth movement. 
1=Prosthesis does not have adequate fit and function that might lead to future tooth and 
tissue damage. 
2=The fit and function of the appliance is of acceptable quality. 
3=Prosthesis is satisfactory in function, design and fit. 
Sum score 0-5= Clinically unacceptable retention and stability 
Sum score 6-9= Clinically acceptable retention and stability 
9.1.5 
Criteria for a Well Made Removable Partial Denture 
The clinical assessment of the suitability of the RPD will be made by an examiner with expert 
knowledge of removable prosthodontics.  The investigator will evaluate each partial denture to 
see if there is adequate occlusal relationship with opposing dentition, missing teeth and/or clasps 
and quality of the denture itself, such as finish, porosity, tissue surface, polish, quality of 
occlusal surface.   
Overall Rating will be rated as: 
Acceptable:  All factors rated “Acceptable” 
Unacceptable:  Any factor is rated “Unacceptable” 
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. 
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9.2.1 
Subject Questionnaire 
On assessment days (visits 2-4), the subject will complete a questionnaire that aims to assess 
the subject’s perceptions of dental/denture cleaning.  The study staff should be mindful that 
whilst the questionnaire does not solicit safety information, any information on safety outcomes 
recorded by subjects on a questionnaire should be evaluated by the investigator to ensure all 
AEs and incidents are recorded.  To ensure that the examiner who performs the gingival and 
plaque assessments is blinded to the assignment of treatment, the examiner will not have access 
to these questionnaires. 
The questionnaire should be completed by the subject prior to any clinical assessments being 
performed. 
A member of site staff will provide verbal instructions to subjects on correct completion prior 
to administration of the questionnaire and should part of the questionnaire not be completed, or 
ambiguous response be given (i.e. more than one answer is given for a question) these be 
clarified with the subject before they leave the study site. All subject responses should be 
entered into the CRF. 
9.2.2 
Partial Denture Cleanliness Index (PDCI) 
The cleanliness of the partial denture should be evaluated by the clinical examiner using the 
PDCI at Visits 2-4 based on the modification of the Clinical Categorization of Denture 
Cleanliness Index, (Blair et al, 1995).  The RPD should have been removed from the subjects’ 
mouth prior to the assessment.  This assessment should be performed as soon as possible after 
removal of the RPD from the mouth and prior to RPD photography (if performed).  No plaque 
disclosing agent should be used.  A suitable dental probe will be used to gently scrape the 
surfaces of the RPD and the PDCI scored using the descriptors detailed in Table 9-1.  All 
surfaces of the RPD should be assessed and the highest score applicable recorded.   
 
Table 9-1 
The Partial Denture Cleanliness Index (PDCI) from (Blair et al, 1995). 
PDCI Score 
Description 
0 
No visible plaque; no matter adherent to the dental probe on light scraping  
1 
No visible plaque; matter adherent to the dental probe on light scraping 
2 
Deposits of plaque just visible on careful examination without need to confirm by 
scraping 
3 
Deposits of plaque clearly visible 
4 
Gross plaque deposits (“velvet appearance”) 
9.2.3 
Modified Gingival Index (MGI) 
The MGI is a non-invasive modification of the original GI (Loe and Silness, 1963) which 
focuses on the visual symptoms of gingivitis (redness, texture, edema) (Lobene, 1986). The 
MGI will be assessed for the facial and lingual/palatal gingiva of all evaluable teeth, four sites 
per tooth (facial surface - papilla and margin; lingual/palatal surface - papilla and margin).  Only 
natural teeth can be assessed.  This means no crowns, bridges, and teeth with fillings (surface 
that has 50% of the surface gradable or no more than 50% of the surface filled) which, in the 
examiner’s judgment, would prevent an accurate grading should be assessed.  Third molars 
should not to be assessed unless, as a result tooth loss, they are functioning as second molars 
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whereby they can be assessed.   The scoring of the MGI will be performed under dental office 
conditions using a standard dental light for illuminating the oral cavity. 
The MGI scoring system will be as described in Table 9-2. 
Table 9-2 
The Modified Gingival Index (MGI) 
Score 
Description 
0 
Absence of inflammation 
1 
Mild inflammation: slight change in color, little change in texture of any portion of the 
marginal or papillary gingival unit 
2 
Mild inflammation: criteria as [1] but involving the entire marginal or papillary gingival unit 
3 
Moderate inflammation: glazing, redness, edema, and/or hypertrophy of the marginal or 
papillary gingival unit 
4 
Severe inflammation: marked redness, edema and/or hypertrophy of the marginal or 
papillary gingival unit, spontaneous bleeding, congestion, or ulceration 
The MGI will be assessed by the same examiner on all evaluable teeth at Baseline/Visit 2, Visit 
3 and Visit 4. 
9.2.4 
Bleeding Index (BI) 
The BI (Saxton and Ouderaa, 1989) assesses the number of bleeding points elicited on probing 
as a measure of gingival condition.  The gingivae will be air dried and then the examiner will 
use an Oulix color coded periodontal PCPII 5B Hufreidy or blunt-ended Community 
Periodontal Index (CPI) probe to assess bleeding.  The probe will be gently inserted into the 
gingival crevice to a depth of approximately 1 millimeter (mm) and then run around the tooth 
(at angle of ~ 60º to the long axis of the tooth), gently stretching the epithelium while sweeping 
from interproximal to interproximal along the sulcular epithelium.  Minimum force should be 
used to avoid damage to the gingival tissue.  The BI will be assessed on the facial and lingual 
gingival surfaces of each scorable tooth.  Only natural teeth can be assessed.  This means no 
crowns, bridges, and teeth with fillings (surface that has 50% of the surface gradable or no more 
than 50% of the surface filled) which, in the examiner’s judgment, would prevent an accurate 
grading should be assessed.  Third molars should not to be assessed unless, as a result tooth 
loss, they are functioning as second molars whereby they can be assessed.   The scoring of the 
MGI will be performed under dental office conditions using a standard dental light for 
illuminating the oral cavity. 
Three scores (according to the scale below) should be recorded bucally/labially (distal, body, 
mesial sites) and three scores lingually/palatally (distal, body, mesial sites).  All scorable teeth 
in one quadrant should be probed first (approximately 30 seconds) before recording the number 
of gingival units which bleed.  The scoring system is described in Table 9-3. 
Table 9-3 
The Bleeding Index (BI) 
Score 
Description 
0 
Absence of bleeding on probing 
1 
Bleeding observed within 30 seconds of probing 
2 
Bleeding observed immediately on probing 
Sites with a score of 1 or 2 will be classified as ‘bleeding’ sites.  The BI will be assessed by the 
same examiner on all evaluable teeth at Baseline/Visit 2, Visit 3 and Visit 4. 
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A repeatability exercise will not be performed for BI. Due to the invasive nature of the BI 
assessment it is not feasible to conduct a repeatability exercise.   
9.2.5 
Turesky Plaque Index (TPI) 
Supra-gingival plaque will be assessed for the facial and lingual/palatal surfaces of all scorable 
teeth, six sites per tooth (mesiobuccal, buccal, distobuccal, mesiolingual/palatal, lingual/palatal 
and distolingual/palatal), using the six site modification of the Turesky Modification of the 
Quigley Hein Plaque Index (TPI) (Lobene et al, 1982), which is weighted towards plaque 
accumulation in the gingival area of the tooth.  
To perform the assessment, the dental plaque will first be disclosed with a plaque disclosing 
solution, rinse with water and expectorate in accordance with the manufacturer’s instructions.  
The same disclosure procedure should be adopted as closely as possible throughout the study. 
Only natural teeth can be assessed.  This means no crowns, bridges, and teeth with fillings 
(surface that has 50% of the surface gradable or no more than 50% of the surface filled) which, 
in the examiner’s judgment, would prevent an accurate grading should be assessed.  Third 
molars should not to be assessed unless, as a result tooth loss, they are functioning as second 
molars whereby they can be assessed.  The TPI will be assessed on the facial and lingual 
surfaces of each scorable tooth. Three scores should be recorded bucally/ labially (distal, body, 
mesial sites) and three scores lingually/ palatally (distal, body, mesial sites).  Disclosed plaque 
will be scored as described in Table 9-4.  The TPI will be assessed by the same examiner on all 
evaluable teeth at Baseline/Visit 2, Visit 3 and Visit 4.  
Table 9-4 
Turesky Plaque Index 
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 
9.2.6 
Oral Hygiene Index 
The Oral Hygiene Index (Greene and Vermillion, 1960) is a composite index based upon a 
calculus and an oral debris assessment.  The Calculus Index (CI) should be performed after the 
MGI and prior to plaque disclosure, whilst the Oral Debris Index (ODI) should be performed 
after the TPI assessment.  Due to the invasive nature of the ODI assessment it is not feasible to 
conduct a repeatability exercise.   
As originally utilized this assessment was performed on a segment basis (6 segments per mouth).  
However, in this study the assessments will be performed on a per tooth surface basis.  This is 
required since the presence of RPDs in the mouth may mean that entire segments are not 
scorable. 
The OHI for each subject will be calculated as the sum score of the mean CI and the mean ODI 
and thus the range of the OHI is 0-6.  
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Each natural tooth will be assessed for ODI and CI.  No crowns, bridges, and teeth with fillings 
(surface that has 50% of the surface gradable or no more than 50% of the surface filled) which, 
in the examiner’s judgment, would prevent an accurate grading should be assessed.  Third 
molars should not to be assessed unless, as a result tooth loss, they are functioning as second 
molars whereby they can be assessed. 
9.2.6.1 
Calculus Index 
The extent of calculus on each tooth surface (buccal and lingual) will be determined by visual 
examination.  Only definite deposits of hard calculus will be recorded.  The CI will be assessed 
on the facial and lingual surfaces of each scorable tooth.   
The CI will be assessed by the same examiner for all subjects throughout the study on all 
evaluable teeth at Baseline/Visit 2, Visit 3 and Visit 4.  The CI will be scored as described in 
Table 9-5 and Figure 9-1.  The CI for each subject will be calculated as the mean score of all 
tooth surfaces (facial/lingual). 
Table 9-5 
The calculus index – from (Greene and Vermillion, 1960) 
Score 
Description 
0 
No calculus present 
1 
Supragingival calculus covering not more than one third of the exposed tooth surface 
2 
Supragingival calculus covering more than one third but not more than two thirds of the 
exposed tooth surface or the presence of individual flecks of subgingival calculus 
around the cervical portion of the tooth or both 
3 
Supragingival calculus covering more than two thirds of the exposed tooth surface or a 
continuous band of subgingival calculus around the cervical portion of the tooth or both 
Figure 9-1 
Diagram demonstrating the calculus index – from (Greene and 
Vermillion, 1960).  Copyright obtained, no further reproduction is 
permitted. 
 
9.2.6.2 
Oral Debris Index 
The extent of oral debris (defined as soft foreign matter on the surface of teeth) on each tooth 
surface (buccal and lingual) will be determined by running the side of a number 5 explorer 
(Shephard’s crook) or similar probe along the buccal, labial and lingual surfaces and noting the 
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occlusal or incisal extent of the debris as it is removed from the tooth surface.  The ODI will be 
scored in accordance with Table 9-6 and Figure 9-2. 
The ODI will be assessed on the facial and lingual surfaces of each scorable tooth.  The ODI 
will be assessed by the same examiner for all subjects throughout the study.  The ODI for each 
subject shall be calculated as the mean score of all tooth surfaces (facial/lingual). 
Table 9-6 
The oral debris index – from (Greene and Vermillion, 1960) 
Score 
Description 
0 
No debris or stain present 
1 
Soft debris covering not more than one third of the tooth surface, or 
the presence of extrinsic stains without other debris regardless of surface area covered 
2 
Soft debris covering more than one third, but not more than two thirds, of the exposed 
tooth surface 
3 
Soft debris covering more than two thirds of the exposed tooth surface 
 
Figure 9-2 
Diagram demonstrating the oral debris index – from (Greene and 
Vermillion, 1960).  Copyright obtained, no further reproduction is 
permitted. 
 
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 oral 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 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.  
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Any abnormality or worsening of a pre-existing condition observed by the clinical examiner or 
reported by the subject from the OST examination carried out at Screening will be recorded as 
an AE. 
Findings from the examination performed at screening will be used to determine subject 
eligibility. 
9.3.2 
Oral Hard Tissue Examination (OHT) 
Where possible, this procedure should be conducted by a single dental examiner or clinically 
qualified designee for all subjects.  The OHT examination will be accomplished by direct 
observation, using retraction aids as appropriate and will identify any grossly carious lesions or 
signs of erosive wear, enamel irregularities, tooth fracture, gross decay, decalcification and 
faulty restorations. The presence of any implants, fixed or removable dentures, fixed or 
removable orthodontic braces/bands, fixed orthodontic retainers, full crowns or veneers will be 
recorded. Observations will be listed as either absent or present, and conditions noted as present 
will be described in the CRF. Any change observed by the clinical examiner or reported by the 
subject from the OHT examination carried out at Screening will be recorded as an AE. 
Findings from this examination at Screening will be used to determine subject eligibility. 
9.3.3 
Repeatability Assessments – subset of subjects only 
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. Given both the MGI and the TPI allow accurate repeat 
assessment, repeat assessments will be performed for both clinical measures throughout the 
treatment period (Visits 2-4) to monitor consistency of scoring.  
Depending on subject visit scheduling, every effort will be made to perform at least 2 repeat 
assessments 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 (maximum 60 minutes) between original and 
repeat assessments for a given subject.  No other procedure should be carried out on that subject 
between the first and the repeat assessment. 
Scores from the first assessment must not be visible to the examiner/scribe when the repeat 
assessment is carried out. 
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). 
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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. 
• 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: 
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• 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 
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).  
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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.  
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 
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Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 2 4 0 1 
 
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 K C 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 5  of 8 2  
 
re p orte d usi n g c o n cise m e dical ter mi n ol o g y o n t he C R F as well as o n t he f or m f or c ollecti o n of 
S A E i nf or mati o n.  
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 retaine 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 ar 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 ci rc 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 he 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 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
P P D
P P D

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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 
causality in light of follow-up information and send an SAE follow-up report with the updated 
causality assessment.  
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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 1 2 4 0 1 
 
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 K C 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 8 2  
 
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 ga t 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 n e 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 arra 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 ata 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 d y, 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 ment 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 u st 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 uir 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 otificati 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.  
G S K C H wi ll 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 g ulat 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. 
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 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 1 2 4 0 1 
 
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 K C 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 8  of 8 2  
 
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 master 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 o r 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 wi ll 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 male s u bject w h o be c o mes pre g na nt w hile partici pati n g will be wit h dra w n fr o m t he st u d y.  
1 0. 9  
D efi niti o n of a n d Pr o c e d ur e f or R e p orti n g M e di c al D e vi c e 
I n ci d e nt s 
Me dical de vi ces are bei n g pr o vi de d b y G S K C H f or use i n t his st u d y; t h e me dical de vices i n 
t his st u d y are t he d e nt ure brus hes a n d t he de nt ure clea nsi n g f oa m.  
1 0. 9. 1  
D efi niti o n of a n I n ci d e nt  
A me dical de vic e i nci de nt is a n y malf u n cti o n or deteri or ati o n i n t he c haracteristics a n d/ or 
perf or ma n ce of a d e vice as well as a n y i na de q uac y i n t he la beli n g or t he i nstr ucti o ns f or use 
w hic h,  directl y or i n directl y, mi g ht lea d t o or mi g ht ha ve le d t o t he deat h of a s u bject/ user/ ot her 
pers o n or t o a seri o us det eri orati o n i n his/ her state of healt h.  
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
P P D
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 212401 
 
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 59 of 82 
 
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 
(serious and non-serious), the appropriate AE CRF page and SAE form will be completed and 
reported as per the AE and SAE reporting sections. 
The Incident Report Form will be completed as thoroughly as possible and signed by the 
investigator before transmittal to GSK CH.  It is very important that the investigator describes 
any corrective or remedial actions taken to prevent recurrence of the incident. 
The completed Incident Report Form should be scanned and emailed to the GSK CH Clinical 
Operations Safety Reporting email box with the study number and subject number in the subject 
line of the email immediately and under no circumstance should this exceed 24 hours after 
study site personnel learn of the event. If there is an SAE, the completed SAE form should be 
sent together with this report form.  However, if a copy of the SAE report is sent with this form, 
this does not replace the procedure to report an SAE.  The original Incident Report Form will 
be retained in the investigator study master file.  
The GSK CH Study Manager should be notified of the situation by telephone or email. 
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 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 1 2 4 0 1 
 
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 K C 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 6 0  of 8 2  
 
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 wi ll 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 nn el 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 he 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  
All c o m m u nicati o ns re gar di n g a me di cal de vice i nci de nt s h o ul d be directe d t o war ds t he G S K 
C H st u d y ma na ger.  T he st u d y ma na ger will asses s if f oll o w u p acti o n is re q uire d. 
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.  
1 0. 9. 4  
R e g ul at or y a n d Et hi c s R e p orti n g R e q uir e m e nt s f or I n ci d e nt s  
T o f ulfill re g ulat or y re p orti n g o bli gati o ns w orl d wi de, t he i n vesti gat or is res p o nsi ble f or t he 
detecti o n a n d d oc u me ntati o n of e ve nts meeti n g t h e defi niti o ns of i nci de nt or malf u ncti o n t hat 
occ ur d uri n g all peri o ds of t he st u d y i n w hic h t h e me dical de vice is us e d.  
T he i n vesti gat or will pr o m ptl y re p ort all i nci de nts occ urri n g wit h a n y me di cal de vice pr o vi de d  
f or use i n t he st u d y i n or der f or t h e s p o ns or t o f ulfill t he le gal res p o nsi bilit y t o n otif y a p pr o priate 
re g ulat or y a ut h orities a n d ot her e ntities a b o ut certai n safet y i nf or mati o n relati n g t o me dical 
de vices bei n g use d i n cli nical st u dies.  
T he i n vesti gat or , or res p o nsi ble pers o n acc or di n g t o l ocal re q uir e me nts (e. g. t he hea d of t he 
me dical i nstit uti o n), will c o m pl y wit h t he a p plica ble l ocal re g ulat or y re q uire me nts relati n g t o 
t he re p orti n g of i nci de nts t o t he I R B/I E C. 
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 212401 
 
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 61 of 82 
 
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 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.  
To protect the privacy of subjects, no Personal Information (PI) (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.  
212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 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 1 2 4 0 1 
 
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 K C 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 6 2  of 8 2  
 
A n y c h a n ges or c orrecti o ns t o data will be perf or me d i n t he Electr o nic D ata Ca pt ure ( E D C) 
S yste m, a n d it will i ncl u d e rati o nale f or c ha n ges. T he E D C s yste m has a n a u dit trail, w hic h will 
pr o vi de a c o m plete rec or d of t he c ha n ges a n d c orrecti o ns e n d orse d b y t he I n vesti gat or.  
A d verse e v e nts will be c o de d usi n g Me di cal Di cti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
a n d a n y c o n c o mita nt me dicati o ns ter ms (if a p plica ble) usi n g a n i nter nal v ali date d me dicati o n 
dicti o nar y, 
 
1 1. 2. 1  
D at a Q u eri e s  
Pr o gra m me d e dit c hec ks will be ge n erat e d a ut o maticall y, as t he d ata are bei n g e nt ere d i nt o t he  
s yste m. Re p orts a n d listi n gs o n t he C R F data will als o be r u n, i n a d diti o n t o t he q ueries alrea d y 
pr o gra m me d a n d ge n erate d b y t he s yste m, t o raise ma n ual q ueries as nee d e d f or site 
clarificati o n or c orrecti o n. T he Cli nical Dicti o nar y De vel o p me nt a n d Ma n a g e me nt Gr o u p will 
raise q u eries as n ee d e d o n safet y data t o c o de t he ter ms ( A Es a n d Dr u gs or c o nc o mita nt 
me dicati o n) a p pr o priatel y.  
T he st u d y m o nit or will perf or m o n g oi n g re vie w t he of t he C R Fs i n acc or da n ce wit h t he 
m o nit ori n g pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h orize d site pers o n nel are 
acc urate, c o m plet e, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g c o n d uct e d i n acc or da n ce wit h t he 
c urre ntl y a p pr o ve d p r ot oc ol a n d a n y ot her st u d y a gree m e nts, I C H G C P, a n d all a p plica bl e 
re g ulat or y re q uire me nts. 
A n y q u eries will be ge nerate d i n t he E D C S yste m t o t he I n vesti gat or or desi g nee, e na bli n g t he 
err ors t o be a d dress e d i n parallel wit h Data Ma n a ge m e nt re vie w. T h e s t u d y m o nit or ca n als o 
r u n re p orts a n d listi n gs o n t he C R Fs, t o raise ma n ual q ueries as nee d e d f or site clarificati o n or 
c orrecti o n.  
1 1. 3  
Pr o c e s si n g P ati e nt R e p ort e d O ut c o m e s  
Pa per b ase d p atie nt re p orte d o utc o me ( P R O) dat a ma y be c ollecte d fr o m a diar y, q uesti o n nair e, 
or ot her s pecifie d d oc u m e nt, etc. a n d e ntere d i nt o t he data ma na ge me nt s yste m ( D M S).    
Electr o nic Patie nt re p orte d o utc o me (e P R O) data ma y b e c ollecte d usi n g electr o nic de vi ces a n d 
tra nsferre d el ectr o nicall y t o G S K C H or T hir d-part y D M v e n d or.  
All P R O s o urce data s h o ul d be re vie we d b y t h e st u d y staff a n d t he st u d y m o nit or t o e ns ure 
acc urate tra nscri pti o n of data a n d t hat a n y p ote nti al A Es or c o n c o mita nt m e dicati o ns re p orte d 
o n t hese d o c u me nts are disc usse d wit h t he s u bj ect a n d tra ns cri be d acc uratel y t o t he C R F a n d/ or 
D M S.   P R Os t hat are classe d as s o urce data will be retai ne d b y t he i n v esti gat or a n d tr ue/certifie d 
c o pies ma y be se nt t o a d esi g nat e d ve n d or or G S K C H as re q uire d.  
T o pr otect t he pri vac y of s u bjects, n o Pers o nal I nf or mati o n ( PI) (i ncl u di n g  t he s u bject's n a me 
or i nitials or birt h date) is t o be rec or de d o n a n y P R O/e P R O t hat will be f or war de d t o G S K C H 
or T hir d -Part y V e n d or.  
1 1. 4  
E xt er n al D at a  
E xter nal Data are s u bject data o btai ne d e xter nall y t o t he C R F. T hese data are ge n erate d fr o m 
la b orat or y i nstr u me nts, c o m p uters or ot her s o urces a n d t he n tra nscri be d i nt o a file a n d f or mat 
2 1 2 4 0 1 | Pr ot oc ol 2 1 2 4 0 1 Cli nical Pr ot oc ol 3 0 J ul 2 0 2 0 | T M F- 3 5 1 1 7 | 4. 0
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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 1 2 4 0 1 
 
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 K C 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 6 3  of 8 2  
 
a gree d u p o n b y G S K C H t o i de ntif y t he s u bject a n d ti me p oi nt refere nce d i n t he C R F a n d/ or 
pr ot oc ol.  
A n a gree d q ualit y c o ntr ol pr ocess will be perf or m e d a gai nst t he tra ns cr i be d data t o t he s o urce 
t o e ns ure t he acc urac y of t he tra nscri pti o n. T he tra nscri be d data is tra ns mitte d i n a n a gree d u p o n 
f or mat t o G S K C H. 
Rec o nciliati o n will be perf or me d bet w ee n t he tra nscri be d data a n d t he cli nical data base t o 
e ns ure s u bject a n d ti me p oi nt refere n ce d i n t h e Cli nical Data base m atc h bef ore Cli nical 
Data base Freeze (l oc ki n g of t he data bas e) ca n occ ur.  
1 2  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S  
1 2. 1  
S a m pl e Si z e D et er mi n ati o n  
A s uffici e nt n u m ber of  s u bjects will be scree ne d t o ra n d o mize at least 1 5 0 ( ma xi m u m 1 7 5) 
s u bjects t o e ns ure a p pr o xi matel y 1 2 8 e v al ua ble s u bjects c o m plete t he e ntire st u d y 
1 2. 2  
St ati sti c al M et h o d s a n d A n al yti c al Pl a n  
A d diti o nal details of t he pr o p ose d statistical a nal ysis will be d o c u me nte d i n t he statistical 
re p orti n g a n d a nal ysis pla n ( R A P), w hic h will be writte n f oll o wi n g fi nalizati o n of t he pr ot oc ol 
a n d pri or t o t h e data b ase l oc k a n d st u d y u n bli n di n g.  T he R A P creati o n a n d statistical a nal ysis 
will be perf or me d b y S y n e os Healt h.  
1 2. 2. 1  
D efi niti o n of A n al y si s P o p ul ati o n s  
T he m o difie d i nte nt t o treat ( mI T T) p o p ul ati o n is defi ne d as t h ose s u bjects w h o are ra n d o mize d, 
recei v e at least o ne d ose of st u d y pr o d uct a n d ha ve at least o ne p ost-baseli ne effi cac y 
meas ure me nt p erf or m e d.  
T he Per Pr ot oc ol ( P P) p o p ulati o n will be a s u b set of t he mI T T p o p ulati o n.  S u bjects wit h a 
pr ot oc ol vi olati o n t hat is dee me d t o affect effi cac y f or all efficac y assess me nts will be e x cl u de d 
fr o m t he P P p o p ulati o n.  S u bjects wit h a pr ot oc ol vi olati o n t hat is dee me d t o affect effi cac y f or 
o nl y s o me ( b ut  n ot all) of t he efficac y assess me nts will be part of t he P P p o p ulati o n, b ut t heir 
data will be e x cl u de d fr o m t he assess me nt at w hic h t he pr ot oc ol vi olati o n occ urre d.  
Efficac y a n al ysis will be base d o n t he mI T T p o p ul ati o n.  A P P a nal ysis will be perf or me d o nl y 
if 1 0 % or m ore mI T T s u bjects are e x cl u de d fr o m P P p o p ulati o n. 
T he Safet y p o p ulati o n is defi ne d as all s u bjects w h o are ra n d o mize d a n d h a ve recei ve d at least 
o ne d ose of st u d y pr o d ucts.  
T he re p eata bilit y p o p ulati o n is defi ne d as all s u bjects w h o ha ve a  re p eat cli nical assess me nt 
( M GI or T PI) at a n y visit. 
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12.2.2 
Exclusion of Data from Analysis  
Subjects who deviate from the protocol will be identified and excluded from analyses as agreed 
by the biostatistician and clinical scientist or designee. 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. 
12.2.3 
Demographic and Baseline Characteristics 
The Safety population will be used for demographic and baseline characteristics. Descriptive 
statistics (number of subjects, mean, standard deviation, median, minimum and maximum for 
continuous variables, and frequency and percentage for categorical variables) will be provided 
for demographic, baseline characteristics and dental history.  Medical history will be listed. 
12.2.4 
Study Drug/Product Compliance and Use of Other Therapies 
12.2.4.1 Study Drug/Product Compliance 
The number of subjects exposed to each treatment will be tabulated for the safety population. 
Treatment deviations for individual subjects will be listed and summarized.  The mean number 
of toothbrushing, mouth rinsing and denture cleaning occasions will be summarized by visit 
and treatment group for the safety population. 
12.2.4.2 Prior and Concomitant Medications 
Prior medications, concomitant medications, and other concomitant non-drug therapies will be 
listed for the safety population. 
12.2.5 
Primary Analysis 
The mITT population will be used for the primary analysis.  The primary efficacy endpoint will 
be the Bleeding Index (BI) score after 12 weeks of study treatments.  The BI score will be 
calculated as the average index values over all tooth sites.  An ANCOVA model will be used 
for the primary analysis with treatment, gender, denture material type (acrylic or cobalt chrome), 
and baseline mean overall MGI score (low, high) as factors and the baseline BI score as a 
covariate. The adjusted means of the two treatments, the proportionate reduction for each 
treatment group, and the treatment difference will be provided together with 95% CI and P-
values.  
The null and alternative hypotheses to be tested in the primary analyses are; 
H0: There is no treatment difference in mean BI score after 12 weeks  
H1: There is a treatment difference in mean BI score after 12 weeks 
The assumption of normality and homogeneity of variance in the ANCOVA model will be 
investigated and if violated, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric tests will be performed, and results will be 
compared with the ANCOVA results. If the inferences from the two analyses are similar, then 
both sets of results will be reported and emphasis will be made on the ANCOVA results. In 
case of discrepancies between inferences of the ANCOVA and non-parametric analysis, results 
will be drawn from the non-parametric analysis. 
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A PP analysis will be performed on the primary analysis only if 10% or more mITT subjects 
are excluded from the PP population. 
12.2.6 
Secondary Analyses 
The mITT population will be used for all secondary analyses.  For all of the secondary analyses, 
Normality assumptions in ANCOVA models will be checked and accounted for in the same 
way as for the primary variable. 
12.2.6.1 Number of bleeding sites at Week 6 and Week 12 
Number of bleeding sites will be calculated as the average number of sites with a BI score of 1 
or 2. At each post-baseline visit, the average number of bleeding sites will be analyzed using 
an ANCOVA model with treatment, gender, denture material type (acrylic or cobalt chrome), 
and baseline mean overall MGI score (low, high) as factors and the baseline score as a covariate. 
The adjusted means of the two treatments, the proportionate reduction for each treatment group, 
and the treatment difference will be provided together with 95% CI and P-values.  
12.2.6.2 MGI score at Week 6 and Week 12 
The MGI score will be calculated as the average index value over all tooth sites.  At each post-
baseline visit, the MGI score will be analyzed using an ANCOVA model with treatment, 
gender, and denture material type (acrylic or cobalt chrome) as factors and the baseline MGI 
score as a covariate. Since the baseline MGI score is included as a covariate, the baseline mean 
overall MGI score (low, high) is not required. The adjusted means of the two treatments, the 
proportionate reduction for each treatment group, and the treatment difference will be provided 
together with 95% CI and P-values. 
12.2.6.3 Overall TPI at Week 6 and Week 12 
The overall TPI score will be calculated as the average index value over all tooth sites. At each 
post-baseline visit, the overall TPI score will be analyzed using an ANCOVA model with 
treatment, gender, denture material type (acrylic or cobalt chrome), and baseline mean overall 
MGI score (low, high) as factors and baseline overall TPI score as a covariate. The adjusted 
means of the two treatments and the treatment difference will be provided together with 95% 
CI and P-values.  
12.2.6.4 Interproximal TPI at Week 6 and Week 12 
The Interproximal TPI score will be calculated as the average index value over all interproximal 
tooth sites.  The Interproximal TPI score will be analyzed in a similar manner to the overall TPI 
score. 
12.2.6.5 BI score at Week 6 
The BI score at Week 6 will be analyzed using the same ANCOVA model as used for the 
primary analysis. The adjusted means of the two treatments, the proportionate reduction for 
each treatment group, and the treatment difference will be provided together with 95% CI and 
P-values. 
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12.2.6.6 CI score at Week 6 and Week 12 
The CI score will be calculated as the average index value over all tooth sites. At each post-
baseline visit, the CI score will be analyzed using an ANCOVA model with treatment, gender, 
denture material type (acrylic or cobalt chrome), and baseline mean overall MGI score (low, 
high) as factors and the baseline CI score as a covariate. The adjusted means of the two 
treatments and the treatment difference will be provided together with 95% CI and P-values.  
12.2.6.7 ODI score at Week 6 and Week 12 
The ODI score will be calculated as the average index value over all tooth sites. At each post-
baseline visit, the ODI score will be analyzed using an ANCOVA model with treatment, gender, 
denture material type (acrylic or cobalt chrome), and baseline mean overall MGI score (low, 
high) as factors and the baseline ODI score as a covariate.  The adjusted means of the two 
treatment, and the treatment difference will be provided together with 95% CI and P-values.  
12.2.6.8 OHI score at Week 6 and Week 12 
The OHI for each subject will be calculated as the sum score of the CI and the ODI. At each 
post-baseline visit, the OHI score will be analyzed using an ANCOVA model with treatment, 
gender, denture material type (acrylic or cobalt chrome), and baseline mean overall MGI score 
(low, high) as factors and the baseline OHI score as a covariate. The adjusted means of the two 
treatments and the treatment difference will be provided together with 95% CI and P-values.  
12.2.6.9 PDCI score at Week 6 and Week 12 
The PDCI score will be calculated as the average index values over all subjects. At each post-
baseline visit, PDCI score will be analyzed using an ANCOVA model with treatment, gender, 
denture material type (acrylic or cobalt chrome), and baseline mean overall MGI score (low, 
high) as factors and baseline PDCI score as a covariate.  The adjusted means of the two 
treatments and the treatment difference will be provided together with 95% CI and P-values. 
12.2.7 
Safety Analysis 
All AEs will be coded using MedDRA.  AEs will be categorized as oral and non-oral by the PI, 
or suitably qualified delegate, prior to database lock.  Treatment-emergent adverse event (Oral 
AEs as well as all AEs) will be summarised.  The number of AEs and number of subjects with 
AEs will be listed and tabulated by treatment group.  The results of OST exams will be tabulated.  
Incidents will be listed.  The safety analysis will be performed on the Safety population. 
12.2.8 
Exploratory Analyses 
The following endpoints are all considered exploratory.  The analysis of these endpoints will 
be performed in a similar manner to the primary or secondary analysis described above.  
 
Unless indicated otherwise, the following endpoints will be analyzed using the same 
ANCOVA model with mITT population as used for the primary or secondary analysis. 
• BI associated with abutment teeth at 6 and 12 weeks. 
• Number of bleeding sites associated with abutment teeth at 6 and 12 weeks. 
• TPI associated with abutment teeth (overall and interproximal) at 6 and 12 weeks. 
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• CI associated with abutment teeth at 6 and 12 weeks. 
• ODI associated with abutment teeth at 6 and 12 weeks. 
• OHI associated with abutment teeth at 6 and 12 weeks. 
• MGI associated with abutment teeth at 6 and 12 weeks.  MGI score will be calculated as 
the average index associated with the abutment teeth only.  At each post-baseline visit, the 
MGI score will be analyzed using an ANCOVA model with treatment, gender and denture 
material type (acrylic or cobalt chrome) as factors and baseline MGI score as a covariate.  
As baseline MGI score is included as a covariate, baseline mean overall MGI score (low, 
high) is not required.  Adjusted means of the two treatments, the proportionate reduction 
for each treatment group, and the treatment difference will be provided together with 95% 
CI and P-values. 
• Cleaning Perceptions Questionnaire at 6 and 12 weeks will be summarized and listed. 
Additional details of the proposed statistical analysis will be documented in the RAP. 
• RPD photographs - No analysis will be performed on these photographic images.  These 
will be incorporated into the clinical study report for illustration of the PDCI scale only. 
12.2.9 
Other Analyses 
The Kappa coefficients for MGI & TPI Repeatability Analysis will be performed using the 
repeatability population.  The repeat assessments will be compared to the original assessments.  
The repeat assessments will not be used in any efficacy analysis.  The first and second 
assessments on each analyzed site at a given visit will be cross-tabulated and a weighted Kappa 
coefficient (κ) will be calculated, along with the 95% confidence interval, to assess the intra-
examiner repeatability.  Repeatability will be deemed: 
• Excellent,  
if κ > 0.75 
• Fair to good,  
if 0.4 ≤ κ ≥ 0.75 
• Poor, 
 
if κ < 0.4 
All subjects who have repeatability data will be included in this analysis. 
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. 
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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. 
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. 
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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.  As per the Regulatory Determination for this study, the denture foam cleanser 
is categorized as a medical device and therefore a Non-significant Risk (NSR) application will 
be required as part of the IRB submission to conduct this study in the US. 
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 (ICH, Nov 2016), and applicable local regulatory requirements and laws. 
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.  
The investigator, or a person designated by the investigator, will obtain 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 
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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.  
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.   
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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. 
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs or other 
documents submitted to GSK CH, subjects should not be identified by their names or initials, 
but by an identification code. The investigator should keep a separate log of subjects’ codes, 
names and addresses.  Documents not for submission to GSK CH, e.g. subjects’ written consent 
forms, should be maintained by the investigator in strict confidence. 
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator for 25 years from the issue of the final Clinical Study Report (CSR) 
or equivalent summary, unless local regulations or institutional policies require a longer 
retention period. The minimum retention time will meet the strictest standard applicable to that 
site for the study, as dictated by any institutional requirements or local laws or regulations, GSK 
CH standards/procedures, and/or institutional requirements.   
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK CH of any changes in the archival 
arrangements, including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with the site. 
13.7 
Conditions for Terminating the Study  
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or study product safety problems, or at the discretion of GSK 
CH.  In addition, GSK CH retains the right to discontinue development of the products in the 
range of products under investigation at any time. For multicenter studies (if applicable), this 
can occur at one or more or at all sites.   
If a study is prematurely terminated, GSK CH will promptly notify the investigator.  After 
notification, the investigator must promptly contact all participating subjects and should assure 
appropriate therapy/ follow-up for the subjects.  As directed by GSK CH, all study materials 
must be collected and all CRFs completed to the greatest extent possible. Where required by 
the applicable regulatory requirements, GSK CH should inform the regulatory authority(ies) 
and the investigator should promptly inform the IRB/EC and provide the IRB/EC a detailed 
written explanation of the termination or suspension.  
If the IRB/EC terminates or suspends its approval/favorable opinion of a trial, the investigator 
should promptly notify the GSK CH and provide GSK CH with a detailed written explanation 
of the termination or suspension. 
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Upon completion or premature discontinuation of the study, the GSK CH monitor will conduct 
site closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations including GCP, and GSK CH Standard Operating Procedures. 
14 
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212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
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C CI

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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Nassani MZ, Tarakji B, Baroudi K, et al. Reappraisal of the removable partial denture as a 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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doi: https://doi.org/10.1016/j.jpor.2008.10.003. 
Theilade E, Wright WH, Borglum S, et al. Experimental gingivitis in man ii. A longitudinal 
clinical and bacteriological investigation. J Periodontal Res. 1966;1:1-13. 
Tinanoff N. Review of the antimicrobial action of stannous fluoride. J Clin Dent. 
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A systematic review. Acta Odontologica Scandinavica. 2003;61(6):347-55. 
van der Weijden GA, Hioe KP. A systematic review of the effectiveness of self-performed 
mechanical plaque removal in adults with gingivitis using a manual toothbrush. J Clin 
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PMID: 16128840. 
Van Loveren C. The antimicrobial action of fluoride and its role in caries inhibition. J Dent 
Res. 1990;69 Spec No:676-81; discussion 82-3. Epub 1990/02/01. doi: 
10.1177/00220345900690S131. PubMed PMID: 2179329. 
Van Loveren C. Antimicrobial activity of fluoride and its in vivo importance: Identification of 
research questions. Caries Res. 2001;35(Suppl. 1):65-70. 
Wagner B, Kern M. Clinical evaluation of removable partial dentures 10 years after insertion: 
Success rates, hygienic problems, and technical failures. Clinical oral investigations. 
2000;4(2):74-80. doi: 10.1007/s007840050119. 
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White D, Cox E, Liang N, et al. A new plaque glycolysis and regrowth method (pgrm) for the 
in vivo determination of antimicrobial dentifrice/rinse efficacy towards the inhibition of 
plaque growth and metabolism--method development, validation and initial activity screens. J 
Clin Dent. 1995;6:59-70. 
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15 
Appendix 
15.1 
Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviation 
Abbreviation 
Term 
AE 
adverse event 
ANOVA 
analysis of variance 
ANCOVA 
analysis of covariance 
BDR 
Blinded data review 
BI 
Bleeding Index 
CI 
confidence interval, calculus index 
CPITN 
community periodontal index of treatment needs 
CRF 
case report form 
CSA 
clinical study agreement 
EC 
ethics committee 
EDC 
Electronic data capture 
eCRF 
electronic case report form 
ePRO 
Electronic patient recorded outcome 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FRP 
Females of Reproduction Potential 
GSKCH 
GlaxoSmithKline consumer healthcare 
GCP 
Good Clinical Practice 
IB 
investigator’s brochure 
ICH 
International Conference on Harmonisation 
ID 
identification 
IEC 
Independent Ethics Committee 
IRB 
institutional review board 
IRT 
Interactive Response Technology 
LSLV 
last subject last visit  
MedDRA 
medical Dictionary for Regulatory Activities 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Abbreviation 
Term 
mITT 
Modified intent to treat 
MGI 
Modified gingival index 
N/A 
not applicable 
NSR 
Non-significant risk 
OHI 
Oral hygiene index 
ODI 
Oral debris index 
PDCI 
Partial Denture Cleanliness Index 
PI 
principal investigator 
PI 
Personal information 
PP 
Per protocol 
PRO 
Patient reported outcome 
QC 
quality control 
RAP 
Reporting and analysis plan 
RPD 
Removable partial denture 
RTM 
reduced transport medium 
SAE 
serious adverse event 
SOP 
standard operating procedure 
SRSD 
single reference study document 
SS 
safety statement 
TPI 
Turesky plaque index 
UK 
United Kingdom 
US 
United States 
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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15.2 
Product Usage Instructions 
Please remove your partial denture prior to brushing your teeth and rinsing your mouth. 
Twice per day (morning and evening), you should clean your teeth, then clean your denture, 
then rinse with mouthrinse in that order. 
 
Toothbrushing – Helps remove plaque to keep gums healthy and helps protect teeth from 
decay 
1.  Wet your supplied toothbrush with running tap water. 
2.  Apply the supplied toothpaste along the full length of the brush head. 
3.  Brush all of your teeth with the toothbrush for 2 (two) timed minutes in your usual way. 
4.  Spit out the toothpaste. 
 
Denture Cleanser Foam – Helps to clean bacteria and stain 
from your denture 
1.  Hold partial denture firmly. 
2.  Shake bottle. 
3.  Apply 2 (two) full pumps of foam wash onto partial 
denture, adjust amount if needed. 
4.  Brush for 90 seconds using the supplied denture cleaning 
brush. 
5.  Rinse partial denture thoroughly with running water before 
inserting in the mouth. 
 
Keep the denture foam out of the sight and reach of children.  
Do not use on natural teeth or in mouth.  Do not touch mouth 
or eyes after use.  Wash hands thoroughly after handling.  
May cause an allergic skin reaction, or irritation to the eyes 
and mucous membranes.  If on skin, wash off with plenty of 
water.  If skin or eye irritation occurs, or skin rash occurs: 
discontinue use, wash with plenty of water and get medical 
advice/attention and advise the study site.  In case of an 
allergic reaction, stop using the product and contact your doctor immediately and advise the 
study site.  Avoid breathing mist or vapour. 
 
Mouthrinse - Helps protect you from tooth decay 
1.  Pour out 10ml of the supplied mouthrinse. 
2.  Rinse your mouth with the mouthrinse for 1 timed minute, swishing the rinse vigorously 
around your mouth. 
3.  Spit out the mouthrinse. 
4.  Reinsert your partial denture. 
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15.3 
Dental History 
The Investigator, or medically qualified designee, will take a dental history from each subject 
and document in the CRF.  The dental history will solicit detail on the subject’s RPD, missing 
teeth and the subject’s current oral hygiene routine.  Examples of the type of questions that will 
be asked include:-  
 
• the age of the subjects current RPD 
• the location of the RPD, recorded as the tooth numbers the RPD has replaced 
• whether the subject normally sleeps with the RPD in place 
• the type of the RPD based upon the Kennedy classification 
• the material of the RPD framework (cobalt chrome or acrylic) 
• the subject’s overall satisfaction with their RPD 
• the cause of tooth loss leading to the RPD (e.g. caries, periodontal disease, trauma, other, 
unknown) 
• documentation of missing natural teeth, recorded using tooth numbers 
• identification of abutment teeth, recorded using tooth numbers 
• the toothpaste and mouthrinse the subject currently uses including frequency of use 
• current method of denture cleaning (including frequency, method and name of any 
products used (if any)) 
 
The Kennedy classification (Miller, 1970) describes the type of partial denture worn as: 
• Class I (bilateral free ended saddle; partially edentulous) 
• Class II (unilateral free ended saddle; partially edentulous) 
• Class III (unilateral bounded saddle; partially edentulous) 
• Class IV (bilateral bounded anterior saddle; partially edentulous) 
 
Examples of the 4 Kennedy classes are shown in Figure 15-1.  For complex RPDs described as 
e.g. Kennedy Class II with modification I, only the primary class will be recorded, i.e. as 
Kennedy Class II. 
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Protocol Number: 212401 
 
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Figure 15-1 
Examples of the 4 Kennedy classes of RPDs. 
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GSK Consumer Healthcare 
 
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Protocol Number: 212401 
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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212401 | Protocol 212401 Clinical Protocol 30 Jul 2020 | TMF-35117 | 4.0