In Situ Erosion Study to Investigate the Effectiveness of an Experimental Toothpaste

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03296072
• Collaborator: (none)
• Enrollment: 62
• Location: 1
• Arms: 3
• Actual Duration (Months): 2.1
• Patients Per Site Per Month: 29.5

Study Details

Study Description

Brief Summary

This will be a randomized, controlled, single center, single- blind, 3 period, 3 treatment, cross-over, in situ design which consists of placing pre-eroded bovine enamel specimens intra orally using a palatal appliance and testing the remineralizing performance of the experimental (dentifrice containing 0.254 Percent weight by weight [%, w/w] sodium fluoride (1150 parts per million [ppm] fluoride) and 5% KNO3 [potassium nitrate]), comparator (dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride) and placebo (Fluoride free placebo containing 5% KNO3 [0 ppm fluoride] ) dentifrices 2 and 4 hours (hrs) post treatment application, based on surface micro hardness measurements. This study will be carried out in healthy adults with a maxillary dental arch suitable for the retention of the palatal appliance.

Condition or Disease	Intervention/Treatment	Phase
Tooth Erosion	Drug: 0.254% w/w sodium fluoride and 5% KNO3; Drug: 0.454% w/w stannous fluoride; Drug: 5% KNO3	Phase 3

Detailed Description

The aim of this study is to investigate the performance of an experimental dentifrice formulation in promoting enamel remineralization and inhibiting post-treatment enamel demineralization in an in situ erosion model, in comparison with a fluoride-free placebo and with a marketed competitor dentifrice product. The study will have 4 visits, 1 screening visit to assess participants eligibility and 3 treatment visits to assess product efficacy, where the treatment product will be dispensed and used under the supervision of a suitably trained study site personnel. Prior to each treatment visit, there will be a washout period of a minimum of 3 days. During this period participants will use their own dentifrice for at least one day, and a fluoride free dentifrice (provided) for two days prior to the next scheduled visit (including in the morning of the scheduled visit) to minimize any carry-over effects of the fluoride toothpaste.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: Laboratory sample analyst will be blinded to treatment received. All study products will be overwrapped to conceal any labelling. The dispensing staff will not be involved in any clinical assessments or laboratory analysis during the study. Dental examiner will also be blinded to the treatment received.
• Primary Purpose: Treatment
• Official Title: A Randomized, Examiner Blind, Crossover, in Situ Erosion Study to Investigate the Efficacy of an Experimental Dentifrice in Remineralization of Previously Softened Enamel Compared to a Placebo Dentifrice
• Actual Study Start Date: Nov 13, 2017
• Actual Primary Completion Date: Jan 16, 2018
• Actual Study Completion Date: Jan 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test product Participants will apply a full ribbon of the test product (1.5 grams [g]) containing 0.254% w/w sodium fluoride and 5% KNO3.	Drug: 0.254% w/w sodium fluoride and 5% KNO3; Dentifrice containing 0.254% w/w sodium fluoride (1150 ppm fluoride) and 5% KNO3; plus 0.25% PVM/MA copolymer and 2.5% sodium lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 millilitres [mL] of tap water for 10 seconds before expectorating again.
Active Comparator: Comparator Product Participants will apply a full ribbon of the comparator product (1.5 g orally) containing 0.454% w/w stannous fluoride.	Drug: 0.454% w/w stannous fluoride; Dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.
Placebo Comparator: Placebo Product Participants will apply a full ribbon of the placebo (1.5 g orally) containing 5% KNO3.	Drug: 5% KNO3; Fluoride free placebo dentifrice containing 5% KNO3 (0 ppm fluoride), 0.25% PVM/MA copolymer and 2.5% lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.

Outcome Measures

Primary Outcome Measures

1. % Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel) [After 4 hrs following single exposure of treatment]

   The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.

Secondary Outcome Measures

1. % Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel) [After 4 hrs following single exposure of treatment]

   The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.

2. Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel) [After 4 hrs following single exposure of treatment]

   The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.

3. % SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride) [After 4 hrs following single exposure of treatment]

   The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.

4. % RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride) [After 4 hrs following single exposure of treatment]

   The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.

5. EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride) [After 4 hrs following single exposure of treatment]

   The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent.

• Male and female participants who, at the time of screening, are between the ages of 18 and 65 years, inclusive.

• Participant who is willing and able to comply with scheduled visits, treatment plan, and other study procedures.

• Good general and mental health with, in the opinion of the investigator or medically qualified designee. No clinically significant and relevant abnormalities in medical history or oral examination.

• Male participant able to father children and female participant of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for 5 days after the last dose of assigned treatment.

• Good oral health without lesions of the oral cavity that could interfere with the study evaluations.

• Maxillary dental arch suitable for the retention of the palatal appliance

• Unstimulated salivary flow rate of at least 0.2 mL/minute and a stimulated salivary flow rate of at least 0.8 mL/minute.

• Understands and is willing, able and likely to comply with all study procedures and restrictions.

Exclusion Criteria:

• Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are GSK employees directly involved in the conduct of the study.

• Participation in other studies involving investigational drug(s) within 30 days prior to screening visit.

• Participation in other studies involving investigational oral care or cosmetic products within 30 days prior to screening visit.

• 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 participant inappropriate for entry into this study.

• Pregnant female participant (self - reported).

• Breastfeeding female participant.

• Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. Unwilling or unable to comply with the lifestyle guidelines described in this protocol.

• Medication that may interfere significantly with the saliva flow in the judgment of the investigator. Should new medications that may interfere with the saliva flow be added, a second salivary flow test will be performed.

• Participant with any condition that would impact on their safety or wellbeing or affect their ability to understand and follow study procedures and requirements.

• Any sign of grossly carious lesions (active), moderate or severe periodontal conditions, or severe tooth wear. Participant presenting at screening with minor caries may continue in the study if their carious lesions are repaired prior to the first treatment visit of the study.

• Wears oral appliance or orthodontia (besides participants wearing permanent lower retainers, which are eligible).

• Recent history (within the last year) of alcohol or other substance abuse. Participant who has previously been enrolled in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Nov 7, 2017
• Statistical Analysis Plan - Feb 27, 2018

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03296072
• Other Study ID Numbers: 208166
• First Posted: Sep 28, 2017
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tooth Erosion; Listerine; Fluorides; Sodium Fluoride; Tin Fluorides

Study Results

Participant Flow

Recruitment Details	Participants were recruited from one center in United States of America.
Pre-assignment Detail	A total of 68 participates were screened, out of which 62 participants were randomized in the study and 6 participants were not randomized as all the 6 participants did not meet study criteria.

Arm/Group Title	Test Product/Comparator Product/Placebo Product	Test Product/Placebo Product/Comparator Product	Comparator Product/Test Product/Placebo Product	Comparator Product/Placebo Product/ Test Product	Placebo Product/Test Product/Comparator Product	Placebo Product/Comparator Product/Test Product
Arm/Group Description	Participants in this arm received test product (0.254% weight by weight [w/w] sodium fluoride [NaF; 1150 parts per million {ppm} fluoride] and 5% potassium nitrate [KNO3]) followed by comparator (0.454% w/w stannous fluoride [SnF2; 1100 ppm fluoride]) and placebo product (5% KNO3 [0 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 grams [g]) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing,for a timed period of 95 seconds. After expectorating the slurry, participants gently rinsed their mouths with 15 milliliters [mL] of tap water for 10 seconds before expectorating again.	Participants in this arm received test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) followed by placebo (5% KNO3 [0 ppm fluoride])and comparator product (0.454% w/w SnF2[1100 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.	Participants in this arm received comparator product (0.454% w/w SnF2[1100 ppm fluoride]) followed by test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) and placebo product(5% KNO3 [0 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.	Participants in this arm received comparator product (0.454% w/w SnF2[1100 ppm fluoride]) followed by placebo (5% KNO3 [0 ppm fluoride])and test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.	Participants in this arm received placebo product (5% KNO3 [0 ppm fluoride]) followed by test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) and comparator product (0.454% w/w SnF2 [1100 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.	Participants in this arm received placebo product (5% KNO3 [0 ppm fluoride]) followed by comparator (0.454% w/w SnF2[1100 ppm fluoride]) and test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.
Period Title: Treatment Period 1
STARTED	10	11	10	10	10	11
COMPLETED	10	11	10	10	10	11
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	11	10	10	10	11
COMPLETED	10	11	10	10	10	11
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	11	10	10	10	11
COMPLETED	10	11	10	10	10	11
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	11	10	10	10	11
COMPLETED	10	11	10	10	10	11
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	11	10	10	10	11
COMPLETED	10	11	10	10	10	11
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Participants
Arm/Group Description	All randomized participants were included for baseline evaluation. Participants applied a full ribbon of the test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3), comparator (0.454% w/w SnF2[1100 ppm fluoride]) and placebo product (5% KNO3 [0 ppm fluoride]) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, participants gently rinsed with 15 mL of tap water for 10 seconds before expectorating again.
Overall Participants	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.4 (13.38)
Sex: Female, Male (Count of Participants)
Female	45 72.6%
Male	17 27.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 6.5%
Not Hispanic or Latino	58 93.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 8.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	14 22.6%
White	42 67.7%
More than one race	1 1.6%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	% Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel)
Description	The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Placebo Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Percentage SMHR]	29.67 (1.12)	21.98 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	7.69
	Confidence Interval	(2-Sided) 95%; 5.18 to 10.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

2. Secondary Outcome

Title	% Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel)
Description	The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Placebo Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Percentage RER]	-23.65 (1.96)	-56.94 (1.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	33.29
	Confidence Interval	(2-Sided) 95%; 28.89 to 37.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

3. Secondary Outcome

Title	Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel)
Description	The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Placebo Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Microgram fluoride per square centimeter]	2.98 (0.09)	1.17 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95%; 1.59 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

4. Secondary Outcome

Title	% SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
Description	The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Comparator Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Percentage SMHR]	29.67 (1.12)	22.10 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	7.57
	Confidence Interval	(2-Sided) 95%; 5.07 to 11.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

5. Secondary Outcome

Title	% RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
Description	The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Comparator Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Percentage RER]	-23.65 (1.96)	-34.63 (1.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	10.98
	Confidence Interval	(2-Sided) 95%; 6.58 to 15.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

6. Secondary Outcome

Title	EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
Description	The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.
Time Frame	After 4 hrs following single exposure of treatment

Outcome Measure Data

Analysis Population Description

The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.

Arm/Group Title	Test Product	Comparator Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.	Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
Measure Participants	62	62
Least Squares Mean (Standard Error) [Microgram fluoride per square centimeter]	2.98 (0.09)	2.01 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Placebo Product
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANOVA
	Comments	From ANOVA with fixed factors for study period and treatment, and a random effect for participant.
Method of Estimation	Estimation Parameter	Difference of Least Square mean
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.

Adverse Events

Time Frame	4 hours
Arm/Group Title	Test Product		Comparator Product		Placebo Product
Arm/Group Description	Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.		Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.		Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.
All Cause Mortality
	Test Product		Comparator Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/62 (0%)
Serious Adverse Events
	Test Product		Comparator Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	Test Product		Comparator Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/62 (12.9%)		6/62 (9.7%)		10/62 (16.1%)
Gastrointestinal disorders
Dental caries	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Lip haematoma	1/62 (1.6%)	1	0/62 (0%)	0	0/62 (0%)	0
Mouth ulceration	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Oral Discomfort	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Oral Mucosal Erthyema	2/62 (3.2%)	2	0/62 (0%)	0	1/62 (1.6%)	1
Oral Pain	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Toothache	1/62 (1.6%)	1	0/62 (0%)	0	1/62 (1.6%)	1
Infections and infestations
Bronchitis	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Gastrointestinal Bactetial Overgrowth	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Herpes Zoster	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Nasopharyngitis	2/62 (3.2%)	2	1/62 (1.6%)	1	0/62 (0%)	0
Sinusistis	1/62 (1.6%)	1	0/62 (0%)	0	0/62 (0%)	0
Urinary Tract Infection	1/62 (1.6%)	1	0/62 (0%)	0	0/62 (0%)	0
Injury, poisoning and procedural complications
Arthopod Bite	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Burn Oral Cavity	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Contusion	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Joint Dislocation	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Palate Injury	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Tooth Fracture	0/62 (0%)	0	1/62 (1.6%)	1	0/62 (0%)	0
Traumatic Ulcer	1/62 (1.6%)	1	0/62 (0%)	0	0/62 (0%)	0
Mouth Injury	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1
Nervous system disorders
Periodic limb movement disorder	0/62 (0%)	0	0/62 (0%)	0	1/62 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.