Clinical trial NCT03965039
Conditions: Dentin Hypersensitivity
Sponsor: Procter and Gamble
Start date: 2019-07-08; Completion date: 2019-10-03
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study is to evaluate the efficacy (changes in dentinal hypersensitivity) and safety (oral soft tissue evaluation) after use of one of four dentifrices in subjects with pre-existing hypersensitivity over an 11-week period.

Detailed description:

Arms: arm 1: Brush twice daily arm 2: Brush Twice Daily arm 3: Brush Twice Daily arm 4: Brush Twice Daily
Interventions: intervention 1: Dipotassium oxalate toothpaste intervention 2: Stannous fluoride toothpaste intervention 3: Potassium nitrate toothpaste intervention 4: Sodium monofluorophosphate toothpaste
Intervention descriptions: intervention 1: Experimental dipotassium oxalate (3%) toothpaste intervention 2: Marketed stannous fluoride (0.454%) toothpaste intervention 3: Marketed potassium nitrate (5%) toothpaste intervention 4: Marketed sodium monofluorophosphate (0.76%) toothpaste

Protocol documents:
Prot_SAP_000.pdf: 
Clinical Study Protocol Study No. 2019079 
CONFIDENTIAL 
Page 1 of 16 
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The Procter & Gamble Company 
Cincinnati, Ohio USA 
A RANDOMIZED CLINICAL STUDY TO ASSESS THE EFFECTS OF VARIOUS DENTIFRICE 
TECHNOLOGIES ON DENTINAL HYPERSENSITIVITY 
23 May 2019 
Protocol Number 2019079 
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. Pejmon Amini 
Silverstone Research Group 
6707 West Charleston, Suite 4 
Las Vegas, NV 89146 
 
 
Investigator’s Agreement Statement: 
I have read, I understand, and I will conduct the study 
according to this Protocol and Good Clinical Practices. 
 
 
 
Dr. Pejmon Amini, DDS 
(D-Mon-Year) 
 
 
 
Signatures below indicate approval of the Protocol. 
Clinical Scientist/Medical 
Monitor 
Malgorzata Klukowska, 
DDS, PhD 
Phone: (513) 622-3726 
 
 
 
 
Malgorzata Klukowska 
(D-Mon-Yr) 
 
 
 
Clinical Trial Manager 
Jill Peters, MBA 
Phone: (513) 622-2489 
 
 
 
 
Jill Peters 
(D-Mon-Yr) 
 
 
 
 
Statistician 
Yuanshu Zou, PhD 
Phone: (513) 622-0555 
 
 
 
 
Yuanshu Zou  
(D-Mon-Yr) 
 
 
 
 
Clinical Data Manager 
Marsha Gabbard, AA 
Phone: (513) 622-0114 
 
 
 
 
Marsha Gabbard 
(D-Mon-Yr) 
 
 
 
 
Associate Director 
Global Oral Care Clinical 
Operations  
Svetlana Farrell, DDS, PhD 
Phone: (513) 622-3680 
 
 
 
 
Svetlana Farrell 
(D-Mon-Yr) 
PII 
PII 
PII 


Clinical Study Protocol Study No. 2019079 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................... 3 
PROTOCOL BODY .................................................................................................................... 4 
1. 
Study Objective ................................................................................................................................ 4 
2. 
Overall Study Design and Plan ........................................................................................................ 4 
*Questionnaire will be analyzed outside of the database. ............................................................... 5 
Screening/Baseline Visit 1 ............................................................................................................... 5 
Day 3, Visit 2 .................................................................................................................................... 5 
Week 2 (+/- 2 days), Visit 3 .............................................................................................................. 5 
Week 4 (+/- 2 days), Visit 4 .............................................................................................................. 6 
Week 8 (+/- 2 days), Visit 5 .............................................................................................................. 6 
Week 11 (+/- 2 days), Visit 6 ............................................................................................................ 6 
Subject Accountability ...................................................................................................................... 6 
General Comments and Adverse Event Recording ......................................................................... 6 
3. 
Inclusion Criteria .............................................................................................................................. 7 
4. 
Exclusion Criteria ............................................................................................................................. 7 
5. 
Continuance Criteria ........................................................................................................................ 8 
6. 
Identity of Investigational Product(s) ................................................................................................ 8 
7. 
Method of Assigning Subjects to Treatment Groups ....................................................................... 8 
B&A Program ................................................................................................................................... 9 
8. 
Product Usage ................................................................................................................................. 9 
9. 
Blinding, Labeling, and Shipping Plan ............................................................................................. 9 
10. Determination of Sample Size ....................................................................................................... 10 
11. Safety Variables ............................................................................................................................. 10 
Safety Observations and/or Measurements................................................................................... 10 
Oral Examination ............................................................................................................................ 10 
12. Efficacy Variables ........................................................................................................................... 10 
Yeaple Probe Calibration ............................................................................................................... 10 
Tactile Threshold Determination .................................................................................................... 10 
Cold Air Challenge ......................................................................................................................... 11 
Schiff Index Sensitivity Scale ......................................................................................................... 11 
13. Hypothesis ..................................................................................................................................... 11 
14. Statistical and Analytical Plans ...................................................................................................... 11 
APPENDIX ............................................................................................................................... 13 
Adverse Event Reporting .................................................................................................................... 13 
Advertising ........................................................................................................................................... 13 
Data Collection .................................................................................................................................... 13 
Case Report Forms ............................................................................................................................. 13 
Source Documents .............................................................................................................................. 14 
Protocol Amendments/Changes ......................................................................................................... 14 
Good Clinical Practices ....................................................................................................................... 14 
Institutional Review ............................................................................................................................. 14 
Investigator Final Report ..................................................................................................................... 14 
Records Retention ............................................................................................................................... 15 
Serious Adverse Event Reporting ....................................................................................................... 15 
Study Medication Dispensing and Storage ......................................................................................... 15 
Subject Consent .................................................................................................................................. 15 


Clinical Study Protocol Study No. 2019079 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
AE(s) 
Adverse Event(s) 
B&A 
Balance & Assignment 
CFR 
Code of Federal Regulations 
CRF(s) 
Case Report Form(s) 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
SOP(s) 
Standard Operating Procedure(s) 
 


Clinical Study Protocol Study No. 2019079 
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PROTOCOL BODY 
1. Study Objective 
The objective of this study is to evaluate the efficacy (changes in dentinal hypersensitivity) and 
safety (oral soft tissue evaluation) after use of one of four dentifrices in subjects with pre-existing 
hypersensitivity over an 11-week period.  
2. Overall Study Design and Plan 
This is a randomized, controlled, single center, double-blind study to assess efficacy (the changes 
in dentinal hypersensitivity) and safety (oral soft tissue evaluation) of four dentifrices with different 
desensitizing technologies over 8 weeks of assigned product use, followed by three weeks of 
washout product use (Colgate Cavity Protection).  After informed consent, approximately 150 
subjects with a history of tooth sensitivity will be evaluated to enroll a target population of 
approximately 120 healthy adult volunteers with current dentinal hypersensitivity.  Subjects will 
be randomized to either an experimental potassium oxalate dentifrice, marketed potassium nitrate 
dentifrice, marketed stannous fluoride dentifrice, or a regular anticavity dentifrice (negative 
control). Subjects will use assigned product for 8 weeks. After 8 weeks, all subjects will use 
Colgate Cavity Protection and come back 3 weeks later (Week 11) to have their dentinal 
hypersensitivity re-evaluated.    Dentinal hypersensitivity will be measured by a standard thermal 
challenge (cold air response measure via Schiff Index) and probing force (calibrated Yeaple 
probe).  Measurements will be taken at Baseline (before any treatment), Day 3, Week 2, Week 4, 
Week 8 and Week 11.  Safety will be assessed from clinical examination of the oral soft tissue. A 
digital image of the oral soft tissue and hard tissue may be taken, at the discretion of the examiner. 
PROCEDURE 
VISIT 1 
SCREENING/BASELINE 
VISIT 2 
DAY 3 
VISIT 3 
WEEK 2        
(2 DAYS) 
VISIT 4 
WEEK 4 
 (2 DAYS) 
VISIT 5 
WEEK 8 
 ( 2 DAYS) 
VISIT 6 
WEEK 11  
( 2 DAYS) 
Informed Consent 
X 
 
 
 
 
 
Medical History Review 
X 
 
 
 
 
 
Confidentiality Disclosure 
Agreement (CDA) 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Questionnaire* 
X 
 
 
 
X 
 
Documentary Image 
(optional) 
X 
X 
X 
X 
X 
X 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
Continuance Criteria 
 
X 
X 
X 
X 
X 
Oral Examination 
X 
X 
X 
X 
X 
X 
Tactile Challenge 
X 
X 
X 
X 
X 
X 
Cold Air Challenge  
X 
X 
X 
X 
X 
X 
Product Distribution 
X 
 
 
 
X 
 
Wash-out Product 
Distribution  
 
 
 
 
X 
 
Product Usage 
Instructions 
X 
 
 
 
X 
 


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Post Treatment Oral 
Exam 
X 
 
 
 
 
 
Product Return  
 
 
 
 
X 
X 
General Comments 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
Subject Accountability 
 
 
 
 
 
X 
*Questionnaire will be analyzed outside of the database.   
Screening/Baseline Visit 1 
Subjects will be asked to read and sign duplicate copies of the informed consent form which will 
be witnessed by site staff.  Subjects will be given one signed copy of the informed consent form 
and the other signed copy will be maintained as site source documentation.  Subjects will be 
asked to complete a confidentiality disclosure agreement.  Personal medical history information 
will be reviewed and retained as site source documentation. Subjects will be asked to complete 
a questionnaire regarding their tooth sensitivity.  All screening data collected will be recorded on 
site source documentation.  Demographic information and entrance criteria will be assessed.  A 
comprehensive oral examination will then be conducted to evaluate the oral and perioral region, 
including hard and soft tissues.  Tactile sensitivity will be assessed using a standard calibrated 
Yeaple probe beginning at 10 g probing force.  Approximately 5 minutes later, thermal sensitivity 
will be assessed using a standard cold air challenge (Schiff Index).  For each subject, 2 test teeth 
will be selected by the clinician for the study.  Eligibility will be determined via a Schiff score >1 
and Yeaple probe score between 10-20 g.  If the qualifying eligible teeth are in the same quadrant, 
the two test teeth should be separated by at least 2 other teeth.  Data for subjects with 2 qualifying 
teeth will be transcribed from source documents into the study database.   
Qualifying subjects will be randomly assigned to either an experimental potassium oxalate 
dentifrice, marketed potassium oxalate dentifrice, marketed stannous fluoride dentifrice, or a 
regular anticavity dentifrice (negative control) to use at home daily for the first 8 weeks of the 
study.  Subjects will complete their first brushing supervised onsite.  Subjects will then receive a 
post-treatment oral examination approximately 5 minutes after brushing.   
Screening and Baseline may be conducted at separate visits based on logistical considerations. 
All general comments, and AE’s if any, will be recorded on the appropriate eCRF.   
Day 3, Visit 2 
Subjects will return to the site after 3 days. Continuance criteria will be assessed.  A 
comprehensive oral examination will then be conducted to evaluate the oral and perioral region, 
including hard and soft tissues.  Tactile sensitivity will be assessed using a standard calibrated 
Yeaple probe beginning at 10 g probing force.  Approximately 5 minutes later, thermal sensitivity 
will be assessed using a standard cold air challenge (Schiff Index). All general comments and 
AEs, if any, will be recorded on the appropriate eCRF.   
Week 2 (+/- 2 days), Visit 3 
Subjects will return to the site after 2 weeks. Continuance criteria will be assessed.  A 
comprehensive oral examination will then be conducted to evaluate the oral and perioral region, 
including hard and soft tissues.  Tactile sensitivity will be assessed using a standard calibrated 


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Yeaple probe beginning at 10 g probing force.  Approximately 5 minutes later, thermal sensitivity 
will be assessed using a standard cold air challenge (Schiff Index). All general comments and 
AEs, if any, will be recorded on the appropriate eCRF. 
Week 4 (+/- 2 days), Visit 4 
Subjects will return to the site after 4 weeks. Continuance criteria will be assessed.   A 
comprehensive oral examination will then be conducted to evaluate the oral and perioral region, 
including hard and soft tissues.  Tactile sensitivity will be assessed using a standard calibrated 
Yeaple probe beginning at 10 g probing force.  Approximately 5 minutes later, thermal sensitivity 
will be assessed using a standard cold air challenge (Schiff Index). All general comments and 
AEs, if any, will be recorded on the appropriate eCRF 
Week 8 (+/- 2 days), Visit 5 
Subjects will return to the site after 8 weeks and will bring their kit box with them.  Continuance 
criteria will be assessed, and subjects will be asked to complete a post-treatment questionnaire.  
A comprehensive oral examination will then be conducted to evaluate the oral and perioral region, 
including hard and soft tissues.  Tactile sensitivity will be assessed using a standard calibrated 
Yeaple probe beginning at 10 g probing force.  Approximately 5 minutes later, thermal sensitivity 
will be assessed using a standard cold air challenge (Schiff Index). All general comments and 
AEs, if any, will be recorded on the appropriate eCRF.  Subjects will return treatment products 
and will be given a new kit box with washout product to use for three weeks. 
Week 11 (+/- 2 days), Visit 6 
Subjects will return to the site after 11 weeks and will bring their kit box with them.  Continuance 
criteria will be assessed.  A comprehensive oral examination will then be conducted to evaluate 
the oral and perioral region, including hard and soft tissues.  Tactile sensitivity will be assessed 
using a standard calibrated Yeaple probe beginning at 10 g probing force.  Approximately 5 
minutes later, thermal sensitivity will be assessed using a standard cold air challenge (Schiff 
Index). All general comments and AEs, if any, will be recorded on the appropriate eCRF.  Subjects 
will receive a bottle of Crest Kids Anti-Cavity fluoride rinse to take home and use at their discretion.  
Subjects will return wash-out products, and a subject accountability form will be completed.   
Subject Accountability 
A subject accountability form will be completed for each subject.  If, for any reason, a subject 
does not complete the study, an explanation will be entered on the Subject Accountability 
eCRF.  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 oral-related AEs will be recorded.  Any recorded 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.  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.   
Optional Documentary Image 


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Subjects may have a documentary image of their oral cavity taken to document any research 
findings, at the discretion of the examiner.   
3. Inclusion Criteria 
In order to be included in the study, each subject must: 
1. be at least 18 years of age; 
2. provide written informed consent prior to participation and be given a signed copy of the 
informed consent form; 
3. sign a Confidentiality Disclosure Agreement (CDA); 
4. be in good general health as determined by the Investigator/designee;  
5. agree not to participate in any other oral/dental product studies during the course of this study; 
6. agree to delay any dentistry (including dental prophylaxis) until the study has been completed; 
7. agree to refrain from the use of any non-study oral hygiene products*;  
8. exhibit adequate oral hygiene (i.e., brush teeth daily and exhibit no signs of oral neglect); 
9. have an absence of extensive calculus above the gum line; 
10. agree to return for all scheduled visits and follow study procedures; and 
11. have two teeth with a Schiff sensitivity score > 1 in response to air challenge and a Yeaple 
probe score of 10-20 g in response to tactile challenge. (If these two eligible teeth are located 
in the same quadrant, they have to be separated by 2 other teeth.) 
 
* Regular floss users will be permitted to continue flossing in their customary manner. However, 
those subjects who do not report regular floss use will not be permitted to floss for the duration 
of the study.  
4. Exclusion Criteria 
Subjects are excluded from study participation where there is evidence of: 
1. having taken anti-inflammatory, analgesic, or psychotropic drugs, chronically; 
2. chronic medical debilitating disease associated with constant or intermittent episodes of daily 
pain; 
3. any home-care bleaching, whitening products or have had a professional bleaching treatment 
within 4 weeks of the Baseline visit; 
4. dental prophylaxis within 2 weeks prior to Baseline visit; 
5. having received professional desensitizing treatment or having used over-the-counter 
desensitizing products within 6 weeks of the Baseline visit; 
6. having periodontal surgery, orthodontic treatment, or teeth restored in the preceding three 
months; 
7. having teeth or periodontium with pathology or defects likely to cause pain; 
8. having a history of allergies or hypersensitivity to ingredients in commercial dental products or 
cosmetics; 
9. self-reported pregnancy or lactation; 
10. having self-reported eating disorders, uncontrolled gastroesophageal reflux disease (GERD or 
Acid Reflux), excessive dietary or environmental exposure to acids, or other systemic 
conditions that are predisposing to dentinal hypersensitivity; 
11. history or presence of kidney disorders, kidney stones, have celiac disease, inflammatory 
bowel disease (ulcerative colitis or Crohn's disease), chronic pancreatitis, have had intestinal 


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or weight-loss surgery, or if have stomach or intestinal problems that keep them from absorbing 
certain foods or nutrients; 
12. any diseases or condition that might interfere with the safe participation in the study;  
13. inability to undergo study procedures;  
14. having severe xerostomia; 
15. having had active caries within the 12 months; 
16. having high risk for caries development (rampant caries, multiple dental restorations, crowns 
with compromised margin) per examiners discretion; 
17. teeth will be excluded from study measurements if they: 
• 
have deep, defective, or facial restorations; 
• 
have full crowns, extensive caries, cracked enamel, or are abutment teeth for fixed or 
removable prosthesis; 
• 
present with tendency for spontaneous bleeding; 
• 
have been scaled/root planed or restored within the past 3 months. 
5.    Continuance Criteria 
Subjects may be excluded from the study or the analysis due to: 
1. started taking anti-inflammatory, analgesic, or psychotropic drugs, chronically; 
2. developed chronic medical debilitating disease associated with constant or intermittent 
episodes of daily pain; 
3. a dental prophylaxis or other dentistry since the last visit;  
4. use of any non-study oral hygiene products since the last visit; 
5. reported pregnancy since the last study visit;  
6. participation in any other oral care study since the last visit; or  
7. being unable or unwilling to comply with study procedures since the last study visit.  
6. Identity of Investigational Product(s) 
 
Control: Colgate Cavity Protection toothpaste (0.76% sodium monofluorophosphate) and 
Oral-B® Indicator soft toothbrush.  
 
Experimental Potassium oxalate toothpaste and Oral-B® Indicator soft toothbrush. 
 
Crest Pro-Health Sensitive and Enamel Shield (0.454% stannous fluoride) toothpaste, and 
Oral-B® Indicator soft toothbrush. 
 
Sensodyne Extra Whitening toothpaste (5% potassium nitrate) and Oral-B® Indicator soft 
toothbrush. 
Week 8-11 Washout Product: 
 
ColgateCavity Protection Toothpaste (0.76% sodium monofluorophosphate) and Oral-B® 
Indicator soft toothbrush.  
7. Method of Assigning Subjects to Treatment Groups 
Study 
Design 
N 
n/group 
B&A 
Program 
PRA 
Block 
Size 
Strata 
Cut-offs 
Parallel 
120 
30 per 
group 
 
Yes 
4 
Pre-treatment Schiff 
Index 
 
≤2.5 or >2.5 


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Pre-treatment Yeaple 
Probe 
 
Age 
 
Gender 
 
 
=10 or >10 
 
<40 or ≥40 
 
Male or Female 
B&A Program 
Eligible subjects will be stratified based on the Pre-treatment Schiff Index and Yeaple probe 
sensitivity scores, age, and gender.  Within strata, subjects will be randomly assigned to one of 
the treatment groups using an encoded program supplied by the Sponsor. This assignment 
process and the distribution of test products will be conducted in a protected area that will ensure 
blinding of the examiner to the identity of the test products. Product distribution and product return 
will be recorded on the Product Distribution Log provided by the Sponsor.  Subjects from the 
same household will be assigned to the same treatment group. 
8. Product Usage 
Subjects will be instructed to brush twice daily.  Subjects will be instructed to apply at least a 1-
inch strip of the toothpaste onto the toothbrush and to brush thoroughly for 1 minute and 
expectorate.   
All subjects will be instructed to use only the assigned products in place of normal oral hygiene 
for the duration of the study. 
9. Blinding, Labeling, and Shipping Plan 
The identity of the toothpaste will be disguised.  Kit boxes will contain 2 tubes of toothpaste, 1 
toothbrush, 1 timer and subject instructions.  Week 8 kit boxes will contain 1 tube of toothpaste, 
and subject instructions (subjects will use the same timer from previous kit box) for the 3-Week 
washout period.   
The kit boxes will be labeled with a unique kit number. Control and test kit boxes will be identically 
sized; the kit box labels will be identical except for a unique kit number used for assignment. Kit 
box labels will also contain the study number, emergency phone number, distributor 
name/address, appropriate caution statements, content statement and other information as 
required by internal regulations and clinical SOPs. The shipping containers will be labeled with 
the clinical site address and a content statement listing study number and kit box numbers 
contained within.  Supplemental products will be provided to site.   
The site will be provided with a code breaker report in a sealed envelope.  The sealed code 
breaker report contains documents that list the kit box number or treatment code while the identity 
of the treatment products is hidden by an opaque scratch-off seal.  If the study blind needs to be 
broken, an individual subject’s investigational product may be ascertained by opening the sealed 
code breaker report, locating the subject’s kit box number or treatment code and scratching off 
the opaque seal to reveal the treatment identity.  The sealed code breaker report will be opened 
if a clinically serious AE occurs or management of the subject requires knowledge of the identity 
of the investigational product.  The Investigator should immediately inform the Sponsor that the 
code will be broken and record the date, time and reason for breaking the code in writing.  After 
the study is complete and the study database has been finalized and locked, the site will return 


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the code breaker report to the Sponsor using the self-addressed, stamped envelope provided by 
the Sponsor. 
10. Determination of Sample Size 
Power analyses were conducted with α=0.05, using a 2-sided test. Up to 120 subjects will be 
enrolled in the study assuming ~5% dropout rate. Data were utilized from a similarly designed 
study with the same examiner and endpoints (2018095). Twenty-eight subjects per group 
completing this trial should provide at least 90% power to detect a difference in Schiff mean scores 
of at least 0.80 units between treatments assuming the variability(s) of Schiff score is 0.88.  
Assuming the variability(s) of Yeaple score is 12.44, a sample size of 28 subjects per group should 
provide at least 90% power to detect a difference in Yeaple score of at least 10.97 units between 
treatments.  
11. Safety Variables 
 
Safety Observations and/or Measurements 
Safety will be assessed by the absence of irreversible side effects.   
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.  
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. 
12. Efficacy Variables 
 
Yeaple Probe Calibration 
The Yeaple probe will be calibrated each day subjects are seen and in accordance with the 
site’s internal SOPs.  The settings should be recorded, dated, and initialed by the person 
performing the calibration on an appropriate form.  A new form will not be necessary for each 
calibration; however, care should be taken so as not to use a different day's force settings.  This 
record will serve as the guide for the force setting for that day's examinations. 
Tactile Threshold Determination 
Tactile sensitivity at test teeth will be assessed at the Baseline, Week 2 and Week 4 and Week 
8 visits using the Yeaple probe test. A #16 explorer tip will be used with the Yeaple probe. The 
tip will be kept perpendicular to the root surface of the tooth being tested. The tip will be moved 
horizontally across the facial surface over the sensitive area. Two horizontal sweeps across the 
entire facial surface are made at each force setting. 
At Baseline (before treatment), testing will be performed beginning at 10 g.  The examiner will 
record tactile scores for responding teeth.  After treatment, testing will begin at 10 g and 


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increase by 10 g to a maximum of 50 g.  Each successive challenge shall increase until a "yes" 
response will be repeated.  If a second "yes" is not obtained, the force setting is increased to 
the next step and continued until a force is found which elicits two consecutive "yes" responses, 
which will be recorded as the threshold on the Tactile Sensitivity Score form.  If no sensitivity is 
found up to 50 g, 50 will be recorded as the threshold. 
 
Cold Air Challenge 
A one second application of cold air will be delivered onto each tooth tested from a standard 
dental unit syringe. 
Schiff Index Sensitivity Scale 
The examiner will record the Schiff Index score corresponding to the response to the cold air 
challenge.   
Schiff Index Sensitivity Scale 
SCORE 
CRITERIA 
0 
Tooth/Subject does not respond to stimulus 
1 
Tooth/Subject responds to stimulus, but does not request discontinuation of stimulus 
2 
Tooth/Subject responds to stimulus and requests discontinuation or moves from stimulus 
3 
Tooth/Subject responds to stimulus, considers stimulus to be painful, and requests 
discontinuation of the stimulus 
13. Hypothesis 
 
The following hypotheses will be tested for each post-treatment assessment. 
Null: 
 
 There is no mean score difference between treatment groups. 
Alternative:   
 
There is a mean score difference between treatment groups. 
 
For each treatment group, the following hypothesis will be tested for each post-treatment 
assessment. 
 
Null: 
 
The post-treatment mean is equal to the pre-treatment mean. 
Alternative:   
The post-treatment mean is not equal to the pre-treatment mean. 
The Schiff Index Sensitivity Scale at Week 4 will be of primary interest.  
14. Statistical and Analytical Plans 
The following statistical analyses will be performed for the sensitivity data (Schiff Index and 
Yeaple Tactile Sensitivity).  Sensitivity scores will be averaged amongst test teeth within each 
subject for each assessment before and after treatment.  For each treatment group and 
assessment, mean post-treatment assessments will be compared to pre-treatment using a 
statistical analysis for paired data that is either non-parametric or parametric (e.g., Wilcoxon 
signed rank test or one sample t-test).  For each post-treatment assessment, mean 
comparisons between treatment groups will be analyzed using analysis of covariance with the 


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baseline score as a covariate with either non-parametric or parametric methods.  If necessary, a 
mathematical transformation to the data may be performed to aid statistical assumptions 
associated with parametric analysis methods.  Statistical comparisons will utilize two-sided 
testing with a 5% significance level.  Demographic and safety data will also be summarized.  
Additional statistical methods may be used to further investigate these data. 


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APPENDIX 
Adverse Event Reporting 
Abnormal findings which may qualify as AEs are those that: 1) were not present at Baseline and 
occurred after product usages of any duration, or, 2) were present at Baseline and worsened in 
severity after product usage of any duration.  All AEs will be recorded on the CRF. If a question 
should arise about the causal relationship of an AE to product usage, the Medical Monitor will 
be contacted to make the determination of relatedness.  
An unexpected event is defined as one that is not identified in nature, severity, or frequency in 
the current safety assessment.  The events will be reported to the FDA as required, upon 
receipt of pertinent clinical data and completion of the required forms. 
Any clinically significant abnormal laboratory finding, serious or unexpected AE, or medical 
event which results in the withdrawal of a subject from the study, must be followed to resolution 
with appropriate medical management, or as deemed necessary (with the Sponsor’s 
agreement).   
Advertising 
Any advertisements used in recruitment of subjects must receive prior approval from P&G and 
the Investigator’s IRB.  A copy of the IRB-approved advertising and the documentation thereof 
must be provided to P&G. 
Data Collection 
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. 
Case Report Forms 
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. 


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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 is 
available at the site. Any CRF used as a source document must be identified as such in the 
Investigator Notebook. 
Protocol Amendments/Changes 
Changes to the Protocol following IRB approval affecting the safety of subjects, scope or 
objectives of the investigation, or the scientific quality of the study will be documented as 
amendments.  Such changes will require the Sponsor, Investigator, and IRB approval prior to 
implementation, unless immediate action is required to safeguard subject safety.  Administrative 
or minor changes (e.g., typographical errors, changes in Sponsor personnel, etc.) will be 
documented as revisions but may not need to be submitted as amendments unless required by 
the IRB.  Any change in the Sponsor’s monitoring staff, Clinical Trial Manager or Medical Monitor 
during the conduct of the study, will be reported to the Investigator. 
Good Clinical Practices 
This study is classified non-AMG, non-MPG according to German study classification but 
conducted in compliance with applicable sections of the US Federal Regulations governing 
informed consent (21 CFR 50) and IRBs (21 CFR 56).  The conduct of this study will be in 
accordance with ICH-GCPs as published by the FDA, with the Commission Directive 2005/28/EC 
published by the European Union, and ISO 14155:2011. During the course of the trial, the clinical 
site will allow monitoring by the Sponsor (Clinical Trial Manager or designee) to check compliance 
with the Protocol, regulations and guidelines, adequacy of the equipment and facilities, and 
satisfactory data collection. 
Institutional Review 
Prior to study initiation, the Investigator must obtain institutional review and approval of the 
Protocol, the consent form, and other necessary study-related documents in compliance with 
the US Code of Federal Regulations, Title 21, Part 56 or the ICH-GCPs Consolidated 
Guidelines, Chapter 3 and in compliance with Procter & Gamble SOP QS-CL-05 (“Institutional 
Review Board/Independent Ethics Committee Review and Approval”). The Investigator will 
maintain any original authorization letter(s) and will be available for review by the Sponsor. IRB 
approval letters should include the study title, Sponsor study number, the address of the IRB, 
date of request, and the signature of the IRB chairperson or designate.  Additionally, the letter 
must acknowledge that both the Protocol and consent form have been approved by the IRB.  
The study will not begin until the Sponsor has received confirmation of IRB approval.  The IRB 
shall also review the investigation at least once a year during study execution. The Investigator 
will notify the IRB when the study is terminated and provide confirmation that the study has 
been closed with the IRB to the Sponsor. 
Investigator Final Report 
Following completion of the study, the Investigator shall submit a final report to the Sponsor 
describing the conduct of the study, deviations from planned conduct, early withdrawals and 
subject accountability, adverse events, and other information on study conduct.  The 
Investigator’s IRB may require more frequent status reports. 


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Records Retention 
The Investigator must retain the subject identification codes, informed consent documentation, 
clinical materials inventory, CRFs (paper or electronic media), medical records and other source 
data for a minimum of 2 years after the last regulatory approval has been received or the 
discontinuation of the study.  The Investigator must receive written authorization from the Sponsor 
before destroying any study document. The Investigator will make the records available for 
inspection and copying upon the request of an authorized employee of a government authority or 
the Sponsor, at reasonable times.  In the event the Investigator retires, relocates, or for any other 
reason withdraws from the responsibility for maintaining records for the period of time required, 
custody of the records may be transferred to another person who will accept responsibility for the 
records.  Notice of such a transfer must be given in writing to the Sponsor. 
The Research Participant’s identification codes are a unique identifier assigned by the Principal 
Investigator to each trial subject to protect the Research Participant’s identity and privacy.  The 
identification codes are used in lieu of the Research Participant’s name when the Principal 
Investigator reports all adverse events and other trial related data. These codes will be used on 
all study documents for the Research Participant’s confidentiality (In order to protect the 
confidentiality of information concerning Research Participants, as stated in section 2.11 of the 
International Conference on Harmonization Good Clinical Practice: Consolidated Guideline (ICH-
GCP).) 
Serious Adverse Event Reporting 
A serious adverse event is defined as an event, which suggests a definite hazard or handicap to 
the subjects. Serious adverse events are any events resulting in death, life threatening situation, 
disability or permanent damage, hospitalization or prolongation of existing hospitalization, or 
congenital anomaly/birth defects; events requiring intervention to prevent permanent 
impairment/damage; or other serious (important) medical events. 
When an Investigator is notified of a serious AE, the Investigator must promptly (within 24 
hours) notify the Sponsor (Clinical Trial Manager or the Medical Monitor) of the serious or 
unexpected event, regardless of causality.  Within 5 working days, a written and/or electronic 
report describing the circumstances of the event must be submitted to the Sponsor. The 
Investigator will be responsible for SAE reporting to the IRB.  
Study Medication Dispensing and Storage 
Study products will be 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) will be documented using forms provided by 
the Sponsor or suitable forms provided by the site. Study products will be returned to the Sponsor 
following the trial, or alternatively, they will be destroyed at the clinical site provided the site has 
an existing SOP for the destruction of clinical materials and prior written approval from the 
Sponsor. 
Subject Consent 
The Investigator will obtain written informed consent for each subject prior to 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 and in compliance with Procter & Gamble SOP QS-CL-04 (“Informed 
Consent Form, Ethics Approval and Investigator Use”). Subjects, or their legal guardian, are 


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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.