Clinical trial NCT03546491
Conditions: Dental Plaque
Sponsor: Procter and Gamble
Start date: 2018-05-08; Completion date: 2018-06-22
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The objective of the study is to evaluate anti-plaque efficacy of a preventive treatment gel in a modified 4-day plaque model.

Detailed description:

Arms: arm 1: 0.4% stannous fluoride arm 2: 0.243 % Sodium Fluoride
Interventions: intervention 1: Preventive Gel intervention 2: Marketed Control
Intervention descriptions: intervention 1: 0.4% Stannous Fluoride intervention 2: 0.243% Sodium Fluoride

Protocol documents:
Prot_SAP_000.pdf: 
Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 1 of 16 
The Procter & Gamble Company 
Cincinnati, Ohio USA 
A CLINICAL STUDY TO EVALUATE ANTI-PLAQUE EFFICACY OF A GEL IN A MODIFIED 4-DAY 
PLAQUE MODEL 
 
13 April 2018 
Protocol Number 2018009 
Signatures below indicate approval of the Protocol. 
Sponsor: 
The Procter & Gamble Company 
Worldwide Clinical Investigations—Oral 
8700 Mason-Montgomery Road 
Mason, OH 45040 
Principal or Coordinating Investigator 
Location, Phone, and Fax 
Dr. Tao He, DDS, PhD 
Oral Health Science Center 
8700 Mason-Montgomery Road 
Mason, OH 45040 
(Phone) 513-622-3160 
 
 
Investigator’s Agreement Statement: 
I have read, I understand, and I will conduct the study 
according to this Protocol and Good Clinical Practices. 
 
 
 
Tao He 
 
(D-Mon-Year) 
 
 
 
Signatures below indicate approval of the Protocol.  
Clinical Scientist/Medical 
Monitor 
Tao He, DDS, PhD 
Phone: (513) 622-2159 
 
 
 
 
Tao He 
 
(D-Mon-Yr) 
 
 
 
Clinical Trial Manager 
Aneta Wilberg, BS 
Phone: (513) 622-2777 
 
 
 
 
Aneta Wilberg 
(D-Mon-Yr) 
 
 
 
 
Statistician 
Rachelle Eusebio 
Phone: (513) 626-2306 
 
 
 
 
Rachelle Eusebio 
(D-Mon-Yr) 
 
 
 
 
Clinical Data Manager 
Marsha Gabbard, AA 
Phone: (513) 622-0114 
 
 
 
 
Marsha Gabbard 
(D-Mon-Yr) 
PII 
PII 
PII 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 2 of 16 
 
 
 
 
Section Head 
Oral Care Clinical 
Svetlana Farrell, DDS, PhD 
Phone: (513) 622-3680 
 
 
 
 
(Name) 
(D-Mon-Yr) 
PII 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 3 of 16 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................... 4 
PROTOCOL BODY .................................................................................................................... 5 
1. 
Background Information ................................................................................................................... 5 
2. 
Study Objective ................................................................................................................................ 5 
3. 
Overall Study Design and Plan ........................................................................................................ 5 
4. 
Inclusion Criteria .............................................................................................................................. 8 
5. 
Exclusion Criteria ............................................................................................................................. 9 
6. 
Continuance Criteria ........................................................................................................................ 9 
7. 
Identity of Investigational Product(s) ................................................................................................ 9 
8. 
Method of Assigning Subjects to Treatment Groups ..................................................................... 10 
9. 
Product Usage ............................................................................................................................... 10 
10. Blinding, Labeling, and Shipping Plan ........................................................................................... 11 
11. Determination of Sample Size ....................................................................................................... 11 
12. Safety Variables ............................................................................................................................. 11 
13. Efficacy Variables ........................................................................................................................... 12 
14. Hypothesis ..................................................................................................................................... 13 
15. Statistical and Analytical Plans ...................................................................................................... 13 
APPENDIX ............................................................................................................................... 14 
Advertising ........................................................................................................................................... 14 
Confidentiality ...................................................................................................................................... 14 
Data Collection .................................................................................................................................... 14 
Source Documents .............................................................................................................................. 14 
Good Clinical Practices ....................................................................................................................... 14 
Informed Consent ................................................................................................................................ 15 
Institutional Review ............................................................................................................................. 15 
Monitoring ............................................................................................................................................ 15 
Protocol Amendments/Changes ......................................................................................................... 15 
Study Medication Dispensing, Storage and Accounting ..................................................................... 16 
Study Termination ............................................................................................................................... 16 
Subject Consent .................................................................................................................................. 16 
 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 4 of 16 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
AE(s) 
Adverse Event(s) 
CFR 
Code of Federal Regulations 
CRF(s) 
Case Report Form(s) 
DPIA 
Digital Plaque Image Analysis  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
TMQHPI 
Turesky Modified Quigley Hein Plaque Index 
OST  
Oral Soft Tissue Exam  
SOP(s) 
Standard Operating Procedure(s) 
 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 5 of 16 
PROTOCOL BODY 
1. Background Information 
Oral hygiene products containing chemotherapeutic ingredients such as stannous fluoride have 
been shown to provide anti-plaque and anti-gingivitis benefits. Optimization of the delivery of the 
ingredients to the oral cavity is key to enhance the therapeutic benefits. The present study is 
designed to evaluate the plaque control benefit of an 0.4% SnF2 preventive treatment gel. 
2. Study Objective 
The objective of the study is to evaluate anti-plaque efficacy of a preventive treatment gel in a 
modified 4-day plaque model. 
3. Overall Study Design and Plan 
This will be a controlled, examiner-blind, randomized, 2-treatment, 3-period cross-over 4-day 
partial brushing plaque study. Up to 32 subjects will be enrolled into the study.  Prior to the 
treatment phase of the study, each subject will have a full mouth, supragingival dental prophylaxis 
and be provided with acclimation product.  Before the treatment period, subjects will be randomly 
assigned to a treatment sequence.  At the baseline visit of each period, an Oral Soft Tissue Exam 
(OST), a digital plaque image (DPIA), and a plaque exam using Turesky Modified Quigley-Hein 
Plaque Index (TMQHPI) will be conducted, followed by a polishing on both the lingual and buccal 
surfaces of the teeth. During the treatment phase, subjects will be asked to brush with Crest 
Cavity Protection on their lingual surfaces for 30 seconds, then without expectoration, subjects 
will be instructed to swish with the slurry left in their mouth for 60 seconds.  After that, subjects 
will be asked to spit out the slurry and rinse their mouth with 20 ml water. Subjects assigned to 
the Treatment Gel l Leg will have the  gel applied by site staff. Only subjects assigned to the 
treatment gel will be asked to stay at the site for 15 minutes following the gel application.  On Day 
4, subjects will return for an OST Exam, a digital plaque image (DPIA), and a final plaque exam 
(TMQHPI). At period 2 Day 3, 10 minutes after product usage ,the subjects will be asked to 
provide 5 ml of saliva into a labeled vial. There will be a washout period of approximately 7 days 
between treatment periods to prevent treatment carryover. 
 
 
 
 
 
 
 
 
 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 6 of 16 
                                      Table 1:  Study Schedule by Procedure Type and Visit 
 
*  Period 3 only, or as subjects discontinue participation 
** Period 2 only 
 
Prophylaxis and Acclimation 
Written informed consent will be obtained from each subject and they will be given a copy.  
Personal medical history information will be obtained, reviewed, and retained as site source 
documentation.  Demographic information and inclusion/exclusion criteria will be obtained and 
documented on the appropriate case report form (CRF).  Subjects will receive a dental 
prophylaxis.  Subjects will be given acclimation/washout products to use for the duration of the 
acclimation period.  Subjects will be instructed to brush all of their teeth as they normally do twice 
a day using Crest Cavity Protection dentifrice and an ADA reference manual toothbrush.  
Subjects will be reminded to abstain from chewing gum, flossing, using toothpicks, eating, 
drinking, or performing any oral hygiene after 11:00 p.m. the evening before the Baseline visit of 
each treatment period.  
 
Periods 1, 2, & 3: 
Baseline – Day 0, Morning 
PROCEDURES 
ACCLIMATION
/ 
PROPHYLAXIS 
 
PERIODS 
1, 2, & 3 
WASHOUT 
PERIOD 
DAY 0 
DAY 1 
 
DAY 2 
DAY 3 
DAY 4 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
Continuance Criteria 
 
X 
 
 
 
 
 
 
 
X 
 
Acclimation/Washout Product Distribution 
X 
 
 
 
 
 
 
 
 
X 
 
Prophylaxis 
X 
 
 
 
 
 
 
 
 
 
 
 Oral Soft Tissue Exam 
 
X 
 
 
 
 
 
 
 
X 
 
Digital Plaque Imaging (DPIA) 
 
X 
 
 
 
 
 
 
 
X 
 
Plaque Exam (TMQHPI) 
 
X 
 
 
 
 
 
 
 
X 
 
Lingual/Buccal Polish 
 
X 
 
 
 
 
 
 
 
 
 
Supervised Test Product Usage 
 
X 
 
X 
 
X 
 
X 
 
 
 
At-Home Product Usage 
 
 
X 
 
X 
 
X 
 
X 
 
 
Saliva Collection 
 
 
 
 
 
 
 
X** 
 
 
 
General Comments 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
AEs  
 
 
 
X 
 
X 
 
X 
 
X 
 
Product Return 
 
X 
 
 
 
 
 
 
 
X* 
 
Subject Accountability 
 
 
 
 
 
 
 
 
 
X* 
 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 7 of 16 
Subjects will return their acclimation products and continuance criteria will be assessed.  Subjects 
will have an OST exam. Then subjects will swish with fluorescein for 1 minute, rinse with 
phosphate buffer and have a digital plaque image taken. Immediately following the imaging, the 
subjects will swish their mouth with red disclosing solution for 60 seconds and expectorate.  
Subjects will receive a Turesky modification of the Quigley-Hein Index plaque exam followed by a 
polishing on the lingual and buccal surfaces of their teeth.  At Period 1, subjects will be randomly 
assigned to a treatment sequence. Morning product usage during the treatment period will be 
supervised at the clinic.  Subjects will be instructed to brush only their lingual surfaces for 30 
seconds, then without expectoration, subjects will be instructed to swish with the slurry left in their 
mouth for 60 seconds.  After brushing, the subjects will be instructed to rinse their mouth with 
water. Subjects assigned to the treatment gel will have the gel applied on their maxillary buccal 
and lingual teeth.. Only the subjects assigned to the treatment gel will be instructed to stay at the 
clinic for 15 minutes following the gel application.   Prior to leaving the clinic, subjects will be 
instructed to use their assigned products in the evening at home and to abstain from chewing 
gum, flossing, or using toothpicks until they have completed their plaque exam on Day 4. 
Evening:  Subjects will perform the second product usage at their homes. 
Day 1 
Morning:  Subjects will return to the test site to perform a supervised product usage, as previously 
described. 
Evening: Subjects will perform the second product usage at their homes. 
Day 2 
Morning:  Subjects will return to the test site to perform a supervised product usage, as previously 
described. 
Evening: Subjects will perform the second product usage at their homes. 
Day 3 
Morning:  Subjects will return to the test site to perform a supervised product usage, as previously 
described. At the morning visit on Day 3 visit, subjects will be reminded to abstain from eating, 
drinking and oral hygiene after 11:00 PM. 
Only at Period 2 Day 3 the subjects will be provided with a labeled sterile tube and asked to 
collect 5 ml of unstimulated saliva 10 minutes after product usage. After the saliva is collected the 
tube will be stored on ice. 
Evening: Subjects will perform the second product usage at their homes. 
Final Visit – Day 4, Morning 
Subjects will bring their treatment products with them to the visit.  Continuance criteria will be 
assessed. Subjects will receive an OST exam. Then subjects will swish with fluorescein for 1 
minute, rinse with phosphate buffer and have a digital plaque image taken. Immediately after the 
imaging, the subjects will swish their mouth with red disclosing solution for 60 seconds and 
expectorate.  Subjects will receive a Turesky modification of the Quigley-Hein Index plaque exam.  
Subjects will be allowed to brush the dye off their teeth prior to leaving the clinic. Subjects will 
then be re-issued their acclimation/washout kit and instructed on brushing during the Washout 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 8 of 16 
period.  Finally, subjects will be reminded 1) to perform the evening brushing before 11:00 PM the 
night before their next Baseline visit, 2) to abstain from chewing gum, flossing, using toothpicks, 
eating, drinking, or performing any oral hygiene after 11:00 PM the night before their next 
Baseline visit, and 3) to bring their acclimation/washout kits to their next Baseline visit. 
   
Washout Period 
After the Day 4 plaque examination, subjects will return to using the acclimation/washout 
products provided twice a day for approximately 7 days. 
 
Subject Accountability 
Subjects will complete their participation in this study at the end of Period 3.  A Subject 
Accountability CRF will be completed for each subject as they complete the study or discontinue 
participation in the study.  If, for any reason, a subject does not complete the study, an 
explanation will be entered on the CRF.  All data gathered on the subject prior to discontinuation 
will be made available to the Sponsor. 
 
General Comments and Adverse Event Recording 
General comments and AEs may be recorded at any time during the study.  All serious AEs will 
be recorded.  In addition, non-serious AEs will be recorded.  Any subject reported AE that 
remains unresolved by study end should be followed up until resolution by the Investigator and 
the resolution should be documented as source documentation by the Investigator.  Examiner 
reported AEs will be followed-up at the discretion of the Medical Monitor.  If a subject is 
unreachable to determine whether the AE has been resolved, the attempts to contact the subject 
should be documented as source documentation by the Investigator. 
 
4. Inclusion Criteria 
In order to be included in the study, each subject must: 
• 
Provide written informed consent prior to participation and be given a signed copy of the informed 
consent form; 
• 
Be 18 years of age or older; 
• 
Agree not to participate in any other oral/dental product studies during the study; 
• 
Agree to delay any elective dentistry (including dental prophylaxis) until the study has been 
completed; 
• 
Agree to refrain from the use of any non-study oral hygiene products (subjects who are regular 
flossers will be allowed to floss during acclimation and wash-out periods); 
• 
Agree to use an oral hygiene product that contains stannous fluoride; 
• 
Agree to refrain from any form of non-specified oral hygiene during the treatment period, including 
the use of products such as floss, toothpicks for plaque removal, and chewing gum; 
• 
Agree to refrain from any oral hygiene, eating and drinking after 11:00 PM the evening before 
plaque measurements on Day 0 and Day 4 of the treatment periods; 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 9 of 16 
• 
Agree to return for all scheduled visits and follow study procedures; 
• 
Possess a minimum of 20 natural teeth with scorable facial and lingual surfaces, of which at least 
4 are molars; and, 
• 
Be in good general health, as determined by the Investigator/designee based on a review of the 
health history/update for participation in the study. 
5. Exclusion Criteria 
Subjects are excluded from study participation if they: 
• 
Have a medical condition requiring pre-medication prior to dental procedures; 
• 
Have taken antibiotics within 2 weeks of the acclimation period or anticipate taking antibiotics at 
any time during the study; 
• 
Have a history of allergies or hypersensitivity to dyes or dentifrices that contain stannous fluoride; 
• 
Have removable or orthodontic appliances which interfere with obtaining 20 gradable teeth; 
• 
Have previously demonstrated an inability to comply with study visit requirements; 
• 
Have rampant caries, open or untreated caries, severe gingivitis or advanced periodontitis 
requiring prompt treatment; or, 
• 
Present with any disease or condition(s) that could be expected to interfere with examination 
procedures or the subject’s safe completion of the study. 
6. Continuance Criteria 
Subjects may be excluded from the study or the analysis if they: 
• 
Have taken antibiotics since their Baseline Visit; 
• 
Have participated in any other oral/dental product studies since their Baseline Visit; 
• 
Have received any non-study dentistry (including dental prophylaxis) since their Baseline Visit; 
• 
Have used any oral hygiene products other than the assigned study products (subjects who are 
regular flossers will be allowed to floss during acclimation and washout periods); 
• 
Performed any oral hygiene, ate, or drank after 11:00 PM the night before their visit; 
• 
Have used floss, toothpicks, or chewing gum since their Baseline visit; 
• 
Have been unable or unwilling to comply with product usage instructions for any reason.   
 
Subjects may withdraw or be withdrawn from the study at any time.  Subjects who are withdrawn 
from the study after randomization to treatment and product assignment will not be replaced. 
 
7. Identity of Investigational Product(s) 
 
DENTIFRICE/GEL 
TOOTHBRUSH 
ACCLIMATION/ WASHOUT 
(MARKETED) 
Crest Cavity Protection Regular 
Flavor Toothpaste Sodium Fluoride 
(0.243% sodium fluoride) 
ADA, soft, manual toothbrush 
 
NEGATIVE CONTROL DENTIFRICE 
(MARKETED) 
Crest Cavity Protection Regular 
Flavor Toothpaste Sodium Fluoride 
(0.243% sodium fluoride) 
TREATMENT GEL 
 0.4% Stannous Fluoride Gel  
 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 10 of 16 
8. Method of Assigning Subjects to Treatment Groups 
Study Design 
n 
Number of Treatment 
Periods 
 Treatment Sequences 
Crossover 
32 
3 
ABB 
BAA 
BBA 
AAB 
 
Treatment Sequence Schedule 
Eligible subjects will be randomly assigned to one of the treatment sequences.  Subjects will be 
assigned to a treatment sequence in the order they come to the site for their first Product Usage 
Visit using a Treatment Sequence Schedule.  The site will keep the Treatment Sequence 
Schedule while the study is on-going.  Should a subject miss a treatment period, that treatment in 
the sequence will be skipped. Subjects who drop from the study prior to the randomization to the 
treatment sequence might be replaced. 
9. Product Usage 
 
Investigational Dentifrice/Gel:  
Frequency per 
day 
Twice daily  AM – Supervised at the clinic  
PM -  At home  
Amount of 
Product 
A Full Brush Head of Toothpaste 
Brushing 
30 seconds (lingual surfaces only) 
Rinsing 
60 seconds (swishing with left-over paste in 
mouth) 
Rinse-off 
Rinse with 20 ml water for 30 seconds  
Gel *  
 0.5g of gel on maxillary/buccal and  
 0.5g of gel on maxillary/lingual  
*Only subjects assigned to the gel treatment 
 
Acclimation/Washout Product Use 
During the acclimation and washout periods, subjects will brush their teeth thoroughly twice 
daily as they normally do with the products provided.  Subjects will rinse their mouth with water 
after brushing to remove excess paste. 
Dentifrice usage (Treatment Periods) 
 
AM treatment product usage will be supervised by clinic staff. 
Subjects will be asked to only brush their lingual surface with their assigned dentifrice for 30 
seconds.  Without expectoration, subjects will be instructed to swish with the slurry left in their 
mouth for 60 seconds.  After that, subjects will be asked to spit out the slurry and rinse their 
mouth with 20 ml of water and swish for 30 seconds. Subjects assigned to the gel treatment will 
have the gel applied by a dental professional. Site staff will weigh out 0.5 g of gel and place the 
gel on a polyethylene strip. One strip will be applied on the maxillary buccal and one strip on the 
maxillary lingual side in the mouth. Once the gel has been applied the strip will be immediately 


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 11 of 16 
removed and discarded. Subjects will be instructed to stay at the clinic for 15 minutes following 
the gel application. All subjects will be asked not to eat or drink anything for 30 minutes following 
use of the test products. 
PM treatment usage will be at subject’s home. 
Subjects will be asked to only brush their lingual surface with their assigned dentifrice for 30 
seconds. Without expectoration, subjects will be instructed to swish with the slurry left in their mouth 
for 60 seconds.  After that, subjects will be asked to spit out the slurry and rinse their mouth with 
20 ml water and swish for 30 seconds. Subjects assigned to the gel treatment will be instructed to 
use only the assigned paste. The gel will not be used at the subject’s homes. 
10.  Blinding, Labeling, and Shipping Plan  
Acclimation Kit Boxes 
Subjects will receive 2 tubes of Crest Cavity Protection dentifrice (over-labeled to blind the 
product), one ADA soft manual toothbrush and written usage instructions.  Subjects will use the 
dentifrice for acclimation and washout periods.  A new brush will be distributed at the beginning 
of each washout period.  These items will be shipped in subject kit boxes to the investigational 
site and distributed to the subjects by site personnel.   
Dentifrice Treatment Legs 
Product will be supplied in subject kit boxes.  Each kit will contain 1 over-labeled tube of the 
assigned toothpaste, ADA soft manual toothbrush, and subject instructions.  The shipping 
containers will be labeled with the "ship to" clinical site address and a "content statement" listing 
study number and subject numbers contained within.  Supplemental product (4 boxes) will be 
provided.   
11. Determination of Sample Size 
Up to 32 subjects will be enrolled in the study.  Thirty subjects completing this study will provide 
at least 80% power to detect a mean difference of 0.15 between treatments for the whole mouth 
average TMQHPI score using two-sided testing with a 5% significance level.  This estimate 
assumes the model mean square error is 0.05 or smaller in a 3-period design. 
12. Safety Variables 
Safety Observations and/or Measurements 
Adverse event data will not be solicited by the clinical investigation staff.  However, all 
volunteered AEs that have the potential to be product-related, will be recorded in the AE CRF.  
Safety will be assessed by the absence of irreversible side effects associated with use of the test 
product.  
Oral Examination 
Assessment of the oral soft tissue is conducted via a visual examination of the oral cavity and 
perioral area utilizing a standard dental light, dental mirror, and gauze.  The structures examined 
include the gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal mucosa, 
tongue, floor of the mouth, labial mucosa, mucobuccal/mucolabial folds, lips, and perioral area.  


Clinical Study Protocol Study No. 2018009 
CONFIDENTIAL 
Page 12 of 16 
Assessment of the oral hard tissues will be conducted via a visual examination of the dentition 
and restorations utilizing a standard dental light, dental mirror, and air syringe.  All abnormal 
findings will be recorded and categorized by their location; hard tissue findings will be categorized 
as “other.”  An AE will be recorded if a new abnormal finding is noted after product distribution or 
any previously noted abnormal finding increases in severity during the treatment period. 
13. Efficacy Variables 
Fluorescein Plaque Disclosing Procedure and Digital Plaque Image Analysis (DPIA) Collection 
System and Analysis  
 
Fluorescein Plaque Disclosing Procedure 
• 
Rinse for 10 seconds with 25 ml of phosphate buffer; 
• 
Rinse for 1 minute with 5.0 ml of 1240 ppm fluorescein in phosphate buffer; 
• 
Rinse 3 times for 10 seconds with 25 ml of phosphate buffer. 
Digital Plaque Imaging Analysis Collection 
The photographic system consists of a high-resolution digital camera.  Two Long Wave UV flash 
lights located on each side of a camera provides the lighting.  The unit is connected to a personal 
computer, which records and analyzes the images.  Prior to daily use, the system is standardized 
to assure proper operation.  Additionally, a color standard is centered and imaged prior to 
imaging the subjects.  A digital image of the maxillary and mandibular anterior facial surfaces is 
captured.  Tooth and plaque pixels are quantified in the digital image and the percent plaque area 
on the teeth is calculated. 
Each image is collected in a darkened room.  The subject sits on a stool in front of a chin rest 
used to hold the head still. The subject places the chin on the chin rest and then positions two 
sterile plastic retractors to retract the lips and cheeks.  It is also acceptable for the subject to 
position the retractors, and then place the chin on the chin rest.  The subject is instructed to 
retract the lips and cheeks (toward the ears) as far as possible.  The incisal edges of the front 
teeth are placed about 5mm – 10mm from each other and centered in the camera.  Prior to 
exposure the subject is instructed to draw air through the teeth and to position the tongue away 
from the teeth so that the tongue is not visible.  The image is taken of the lips, teeth and gums 
only; the whole face is not visible in the image.  Each image is saved in a file with the subject ID 
number. 
Plaque Examination 
The plaque deposits on the teeth will be scored on six surfaces (distobuccal, midbuccal, 
mesiobuccal, distolingual, midlingual and mesiolingual) of all 28 teeth (excluding 3rd molars, 
crowns and surfaces with cervical restorations) according to the Quigley-Hein Index as modified by 
Turesky et al which emphasizes plaque in contact with the gingiva.  Buccal, lingual, and whole 
mouth average plaque scores will be calculated for each subject and tooth surfaces by totaling 
the scores and dividing by the number of gradable sites examined.  Scoring criteria are shown in 
Table 3.   
 
Table 3:  Turesky Modified Quigley-Hein Index 


Clinical Study Protocol Study No. 2018009 
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Page 13 of 16 
Score 
Description 
0 
No Plaque 
1 
Separate flecks of plaque at the cervical margin. 
2 
A thin, continuous band of plaque (up to 1 mm) at the cervical 
margin. 
3 
A band of plaque wider than 1 mm, but covering less than one 
third of the side of the crown of the tooth. 
4 
Plaque covering at least one third, but less than two thirds of the 
side of the crown of the tooth. 
5 
Plaque covering two thirds or more of the side of the crown of the 
tooth. 
8 
Non-gradable site 
9 
Missing tooth 
Examiner:  A. Das 
             Red Plaque Disclosing Dye Procedure and Preparation 
Approximately twenty (20) drops of undiluted plaque disclosing solution is dispensed directly from 
the manufacturer’s original bottle into plastic dosage cups. Study Subjects are given the dosage 
cup to swish the disclosing solution orally for 15 seconds and then expectorate. The Subjects 
then rinse with 10ml of tap water for 10 seconds and expectorate. 
Saliva Sample 
Subjects will be asked to expectorate approximately 2 mL of unstimulated saliva into a labeled 
tube.   The subjects will have up to 5 minutes to provide this amount. Collected samples will be 
kept on ice at the site and then frozen at -70C. The saliva samples will be analyzed for tin and 
fluoride outside of the study protocol.  
14. Hypothesis 
For TMQHPI plaque scores (whole mouth, buccal and lingual surfaces) and percent plaque area 
the following hypotheses will be tested. 
Null: 
 
The mean plaque score is equal between the treatments. 
Alternative: 
The mean plaque score is not equal between the treatments. 
15. Statistical and Analytical Plans 
The primary endpoint is the whole mouth average TMQHPI plaque scores. Plaque scores and 
percent plaque area will be analyzed separately for each surface using a general linear mixed 
model.  The statistical model will include treatment and period as fixed effects as well as subject 
as a random effect.  Carryover effect will be assessed and may be included in the model if 
reasonably appropriate.  Baseline may be used as a covariate.  Statistical comparisons will be 
two-sided with a significance level of 0.05.  Additional analyses of the data may be performed. 


Clinical Study Protocol Study No. 2018009 
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Page 14 of 16 
APPENDIX 
Advertising 
If the Oral Health Science Center chooses to advertise for subjects, whether in professional or 
consumer publications, radio, television, or any other means, all advertising must be approved by 
the IRB prior to use, documented, and retained. 
Confidentiality 
Subject files will be maintained in a locked location for the duration of the study.  The recipients 
will treat this information confidentially.  In the event of any publication regarding this study, 
subject identity will not be disclosed. 
Direct access to study records and source data/documentation, including subject medical 
records, will be provided as needed to appropriate parties for the purpose of trial-related 
monitoring, auditing, IRB/IEC review, and regulatory inspection.  Prior to participating in the study, 
subjects will consent, in writing, to the release of their medical records for said purposes. 
Data Collection 
The Data Manager will supply the paper and/or electronic CRFs to be used in this study.  It is the 
responsibility of the Investigator to maintain and submit accurate and timely CRFs to the Sponsor.  
All hard copy CRFs will be filled out legibly in ink.  
All questions should be answered.  For paper CRFs, if an entry requires correction, a single line 
will be placed through the entry so as not to obscure the original record, the corrected entry will 
be initialed and dated by the individual making the change, and a reason will be given for the 
change.  There will be no whiteouts or erasures.  For electronic CRFs, if an entry requires 
correction, the change is made directly to the CRF in the database, the user is prompted to 
provide a reason for the change, and the correction is logged in by an electronic audit trail. 
As necessary, the Data Manager may make specified allowable changes to the database without 
issuing a query to the site, as agreed upon by study site per this protocol. Examples of allowable 
changes include incorrect date formats, incorrect current year recorded (as in the start of a new 
year), and unambiguous spelling errors. Changes to common abbreviations and symbols to 
equivalent text to meet system or coding constraints (e.g., @ = at, ~ = approximately), may also 
be allowable. Values that are ambiguous or open to interpretation will be queried to the sites.  It is 
the responsibility of the Data Manager to ensure all changes are supported by information 
contained elsewhere and/or are unambiguous. 
Source Documents 
The Investigator has the responsibility for ensuring that all source documents (i.e., study and/or 
medical records) and CRFs are completed and maintained according to the study protocol and 
are available at the site.  Any CRF used as a source document must be identified as such in the 
Investigator Notebook. 
Good Clinical Practices 
This study is conducted in compliance with applicable sections of the US Federal Regulations 
governing informed consent (21 CFR 50), IRBs (21 CFR 56), study conduct (21 CFR 312) and 


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the International Conference on Harmonization’s Good Clinical Practice Consolidated Guidelines, 
[ICH-GCPs, as published by the FDA on 9 May 1997, Federal Register, Volume 62, Number 90 
pages 25691-25709]).  During the course of the trial, the clinical site is monitored by P&G staff 
(Clinical Trial Manager or designee) to ensure compliance with the Protocol, regulations and 
guidelines, adequacy of the equipment and facilities, and satisfactory data collection.   
Informed Consent 
A subject consent form will comply with all applicable regulations governing the protection of 
human subjects.  The elements of informed consent and the documentation of informed consent 
are specified in 21 CFR 50.25 and 50.27 and/or ICH GCPs chapter 4.  Each subject must sign 
and date an informed consent to serve as a participant in the study.  A signed copy of the consent 
form will be given to the subject and a signed copy will be retained by the Oral Health Science 
Center.  Subjects may withdraw from participation in the study at any time.  Additionally, the 
Investigator may withdraw subjects from the study if it is in the best interest of the subjects.  The 
reason for all subject withdrawals from the study will be documented on the appropriate CRF. 
Institutional Review 
Prior to study initiation, the Investigator must obtain institutional review and approval of both the 
Protocol and the consent form, in compliance with the US Code of Federal Regulations, Title 21, 
Part 56 or the ICH-GCPs Consolidated Guidelines, Chapter 3.  The Investigator maintains any 
original authorization letter(s) and forwards copies to P&G.  IRB approval letters should include 
the study title, P&G study number, the address of the IRB, date of request, and the signature of 
the IRB chairperson/designate.  Additionally, the letter must acknowledge that both the Protocol 
and consent form have been approved by the IRB, with notification of any changes required.  The 
study does not begin until P&G has received written confirmation of IRB approval.  This IRB shall 
also review the investigation at least once a year during study execution.  The Investigator 
notifies the IRB when the study is terminated. 
Monitoring 
Prior to commencement of the study, an initiation meeting will be held with the appropriate Oral 
Health Science Center personnel to review the objectives and procedures of the clinical trial.  To 
assure accurate, complete, consistent, and reliable data, the Oral Health Science Center and 
study procedures will be monitored by a Clinical Trial Manager in accordance with 21 CFR 312 
and ICH GCPs Chapter 5. 
The Oral Health Science Center study coordinator is expected to contact the Clinical Trial 
Manager or designee as needed regarding study concerns and/or questions. 
Protocol Amendments/Changes 
Changes to the Protocol following Institutional Review Board (IRB) approval affecting the safety 
of subjects, scope/objectives of the investigation, or the scientific quality of the study are 
documented as amendments.  Such changes require P&G, Investigator, and IRB approval prior 
to implementation, unless immediate action is required to safeguard subject safety.  
Administrative/minor changes (e.g., typos, changes in P&G personnel [excluding medical 
monitor], etc.) are documented as revisions but do not have to be submitted as amendments 
unless required by the IRB.  Any change in P&G’s monitoring staff, Clinical Trial Manager or 
Medical Monitor during the conduct of the study, must be reported to the Investigator. 


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Study Medication Dispensing, Storage and Accounting 
Study products are stored in a secure area, under environmental condition as required by label 
instructions or as described in the Protocol, and dispensed only under the authorization of the 
Investigator.  The storage condition shall be properly documented.  Both the receipt and 
dispensation of all test products (used and unused) are documented using forms provided by 
P&G or suitable forms provided by the site.  Study products are returned to P&G following the 
trial, or alternatively, they are destroyed at the clinical site provided the site has an existing SOP 
for the destruction of clinical materials and prior written approval from P&G. 
Study Termination 
The study is terminated upon completion of all subject treatments and evaluation.  The study may 
be discontinued at any time. 
Subject Consent 
The Investigator obtains written informed consent for each subject prior to that subject’s 
participation in the study, per the US Code of Federal Regulations, Title 21, Parts 50.25 and 
50.27 and ICH-GCPs, Chapter 4, subpart 4.8.  Subjects, or their legal guardian, are required to 
read, sign and date an IRB approved consent form with the Investigator also maintaining a signed 
and dated copy.  The subject or legal guardian will be given a copy of the consent form.  All study 
procedures must be explained in non-technical terms.