Evaluation of Plaque Fluid Fluoride Retention From Fluoride Toothpastes

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00708305
• Collaborator: (none)
• Enrollment: 65
• Location: 1
• Arms: 4
• Duration (Months): 4
• Patients Per Site Per Month: 16.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the efficacy of different sodium fluoride (NaF) containing toothpastes in prevention of dental caries. Change from baseline fluoride data at various time points up to four hours after a single brushing with NaF containing toothpastes will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Dental Caries	Drug: Sodium Fluoride (NaF); Drug: Placebo	Phase 3

Detailed Description

Topical fluorides in a wide variety of delivery systems have been proven to be clinically effective in the prevention of dental caries. It is generally agreed that fluoride has its anti-caries effect mainly by decreasing the rate of enamel demineralization and enhancing the rate of enamel remineralization. There is a general consensus that level of fluoride in plaque fluid, may be directly related to the anti caries effects of fluoride. Also, fluoride levels in the oral fluids decrease rapidly after topical fluoride application, mainly due to the diluting and washing effect of saliva followed by periodic swallowing. To evaluate fluoride content, plaque samples will be collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride will be calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of Plaque Fluid Fluoride Retention From Fluoride Toothpastes
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NaF toothpaste (1450 parts per million [ppm] fluoride [F]) Participants brushed for one timed minute with 1.6g of NaF/silica and 0.4 percent carbopol toothpaste containing 1450ppmF as NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Drug: Sodium Fluoride (NaF); Different fluoride toothpastes containing between 1400ppmF - 1450ppmF of fluoride as NaF; Other Names: fluoride
Active Comparator: NaF toothpaste (1400ppmF) Participants brushed for one timed minute with 1.6g of NaF toothpaste containing 1400ppmF as NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Drug: Sodium Fluoride (NaF); Different fluoride toothpastes containing between 1400ppmF - 1450ppmF of fluoride as NaF; Other Names: fluoride
Active Comparator: Sodium monofluorophosphate (NaMFP)/ NaF toothpaste (1450ppmF)) Participants brushed for one timed minute with 1.6g of NaMFP/NaF toothpaste containing 1450ppmF from NaMFP and NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Drug: Sodium Fluoride (NaF); Different fluoride toothpastes containing between 1400ppmF - 1450ppmF of fluoride as NaF; Other Names: fluoride
Placebo Comparator: Placebo toothpaste (0ppmF) Participants brushed for one timed minute with 1.6g of fluoride free toothpaste. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Drug: Placebo; Fluoride free toothpaste (0ppmF)

Outcome Measures

Primary Outcome Measures

1. Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours [Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment]

   To evaluate fluoride content, plaque samples were collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride were calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis. AUC was determined from 0-4hours using trapezoidal rule and natural log transformation was applied due to failure of assumption of normal distribution of data.

Secondary Outcome Measures

1. Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours [Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment]

   To evaluate fluoride content, plaque samples were collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride were calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis. AUC was determined from 0-4 hours using trapezoidal rule and natural log transformation was applied.due to failure of assumption of normal distribution of data.

2. Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments [Plaque samples were collected at baseline, 15 minutes post single application of study treatment]

   Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

3. Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments [Plaque samples were collected at baseline, 30 minutes post single application of study treatment]

   Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

4. Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments [Plaque samples were collected at baseline, 1 hour post single application of study treatment]

   Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

5. Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments [Plaque samples were collected at baseline, 2 hour post single application of study treatment]

   Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

6. Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments [Plaque samples were collected at baseline, 4 hours post single application of study treatment]

   Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Age:Age 18 through 65 years.

2. General Health: Good general health with (in the opinion of the investigator) no clinically significant and/or relevant abnormalities of medical history or oral examination, specifically including diabetes or hypoglycemia.

3. Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions.

4. Consent: Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.

5. Oral: a) Currently living in the Indianapolis, Indiana area and not taking fluoride supplements. b) Have a normal stimulated (= 0.8 ml/min) and unstimulated (= 0.2 ml/min) salivary flow rate. c) Have a full complement of natural teeth with the exception of third molars and teeth extracted for orthodontic reasons. Participants natural teeth must have at least one surface free of restoration in each interproximal embrasure. d) Produce at least 6mg of plaque at Screening Visit 2.

Exclusion Criteria:

1. Pregnancy:Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. No pregnancy test will be required.

2. Breast-feeding:Women who are breast-feeding.

3. Medical History:Current or relevant history of any serious, severe or unstable physical or psychiatric illness that would make the subject unlikely to fully complete the study or any that increases the risk to the subject.

4. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.

5. Clinical Study/Experimental Medication:Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit 1 at the start of the study with the exception of those participating in GSKCH study Z3170476.

6. Medication: a) Currently taking antibiotics or have taken antibiotics in the two weeks prior to any treatment visit or during the study. b) Has a medical condition that would require prophylactic antibiotics prior to a dental cleaning.

7. Dental: a) Current active caries or moderate to severe periodontal disease that may compromise the health of the participants or the study. b) Current use of chlorhexidine mouthrinse.

8. Personnel: An employee of the sponsor or the study site who is directly involved in the conduct of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Dentistry	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00708305
• Other Study ID Numbers: T3508570
• First Posted: Jul 2, 2008
• Last Update Posted: Jan 1, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by GlaxoSmithKline: toothpaste; plaque fluid; fluoride
• Additional relevant MeSH terms: Dental Caries; Listerine; Fluorides; Sodium Fluoride

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the clinical site.
Pre-assignment Detail	There was a four-day wash out prior to each treatment period during which participants used the study fluoride-free toothpaste. Two to three days prior to the start of each treatment visit, participants attended the study site for a dental prophylaxis then discontinued all oral hygiene prior to study treatment visit.

Arm/Group Title	Sodium Fluoride (NaF) Toothpaste(1450 Parts Per Million(Ppm)F)	NaF Toothpaste (1400ppmF)	Sodium Monofluorophosphate (NaMFP)/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6 grams (g) of with NaF and 0.4% carbopol toothpaste (1450 ppm F as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6 g NaF toothpaste (1400 ppm F as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6 g NaMFP and NaF toothpaste (1450 ppm F - 1000 ppm F as NaMFP and 450 ppm F as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6 g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Period Title: Period 1
STARTED	16	16	17	16
COMPLETED	15	16	16	14
NOT COMPLETED	1	0	1	2
Period Title: Period 1
STARTED	15	15	16	15
COMPLETED	14	13	16	14
NOT COMPLETED	1	2	0	1
Period Title: Period 1
STARTED	15	14	14	14
COMPLETED	14	12	14	14
NOT COMPLETED	1	2	0	0
Period Title: Period 1
STARTED	12	14	14	14
COMPLETED	12	14	14	14
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All randomized participants
Overall Participants	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.4 (6.97)
Sex: Female, Male (Count of Participants)
Female	31 47.7%
Male	34 52.3%
Region of Enrollment (participants) [Number]
United States	65 100%

Outcome Measures

1. Primary Outcome

Title	Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours
Description	To evaluate fluoride content, plaque samples were collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride were calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis. AUC was determined from 0-4hours using trapezoidal rule and natural log transformation was applied due to failure of assumption of normal distribution of data.
Time Frame	Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment

Outcome Measure Data

Analysis Population Description

Per-Protocol (PP) population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450 Ppm F)	NaF Toothpaste (1400 Ppm F)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6 g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	57
Least Squares Mean (Standard Error) [ln(μg*F*minutes/cm^2)]	0.54 (0.086)	0.54 (0.087)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis is no difference between treatments in comparison. Tests were 2-sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9762
	Comments	No adjustment was made for multiple comparisons as the primary comparison was predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.00
	Confidence Interval	() 95%; -0.21 to 0.20
	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.

2. Secondary Outcome

Title	Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours
Description	To evaluate fluoride content, plaque samples were collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride were calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis. AUC was determined from 0-4 hours using trapezoidal rule and natural log transformation was applied.due to failure of assumption of normal distribution of data.
Time Frame	Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment

Outcome Measure Data

Analysis Population Description

Per-Protocol (PP) population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	57	58	56
Log Mean (Standard Error) [ln(μg*F*minutes/cm^2)]	0.54 (0.086)	0.54 (0.087)	0.05 (0.086)	-0.90 (0.087)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis is no difference between treatments being compared. Tests were 2 sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment was made for multiple comparisons as the comparisons were predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean DIfference
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.70
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment was made for multiple comparisons because the comparisons were predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.44
	Confidence Interval	() 95%; 1.23 to 1.65
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment was made for multiple comparisons because the comparisons were predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.49
	Confidence Interval	() 95%; 0.28 to 0.70
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment was made for multiple comparisons because the comparison was predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.23 to 1.65
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment was made for multiple comparisons as the comparisons were predefined.
	Method	ANCOVA
	Comments	The model included mean baseline fluoride level for treatment period (covariate), treatment and period as fixed and subject was random factor.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.16
	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	Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments
Description	Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Time Frame	Plaque samples were collected at baseline, 15 minutes post single application of study treatment

Outcome Measure Data

Analysis Population Description

PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	59	60	58
Median (Full Range) [μg*F/g]	2.00 (4.586)	1.56 (2.806)	0.76 (1.633)	0.03 (0.083)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0151
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.12 to 1.72
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.69 to 2.36
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis is no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	3.01
	Confidence Interval	(2-Sided) 95%; 2.06 to 4.05
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.41 to 1.27
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2.10
	Confidence Interval	(2-Sided) 95%; 1.50 to 2.74
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.35
	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	Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments
Description	Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Time Frame	Plaque samples were collected at baseline, 30 minutes post single application of study treatment

Outcome Measure Data

Analysis Population Description

PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	58	60	58
Median (Full Range) [μg*F/g]	0.71	0.72	0.28	0.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5545
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.47
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.71
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.56
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signal Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.68
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.35
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.56
	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	Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments
Description	Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Time Frame	Plaque samples were collected at baseline, 1 hour post single application of study treatment

Outcome Measure Data

Analysis Population Description

PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	58	58	58
Median (Full Range) [μg*F/g]	0.20	0.22	0.12	0.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6865
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.08
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1756
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.12
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.38
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.22
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.51
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.25
	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	Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments
Description	Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Time Frame	Plaque samples were collected at baseline, 2 hour post single application of study treatment

Outcome Measure Data

Analysis Population Description

PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	58	59	58	57
Median (Full Range) [μg*F/g]	0.09	0.09	0.07	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0783
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.00
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0531
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.07
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; 0.07 to 0.14
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.15
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.20
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.10
	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.

7. Secondary Outcome

Title	Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments
Description	Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Time Frame	Plaque samples were collected at baseline, 4 hours post single application of study treatment

Outcome Measure Data

Analysis Population Description

PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the "n" per treatment group. Missing data was not imputed.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds	Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.	Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Measure Participants	57	57	60	57
Median (Full Range) [μg*F/g]	0.04	0.04	0.02	-0.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaF Toothpaste (1400 Ppm F)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4309
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.01
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0726
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.04
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste(1450 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.06
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0107
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.06
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400 Ppm F), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Signed Rank Test
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.07
	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	Wilcoxon Signed Rank Test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.04
	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.

Adverse Events

Time Frame	All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
Arm/Group Title	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with 1.6g of with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.		Participants brushed their natural teeth for one timed minute with 1.6g NaF toothpaste (1400ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.		Participants brushed their natural teeth for one timed minute with 1.6g NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.		Participants brushed their natural teeth for one timed minute with 1.6g fluoride free toothpaste (0ppmF), under the supervision of study staff. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
All Cause Mortality
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		Placebo Toothpaste (0ppmF)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		Placebo Toothpaste (0ppmF)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		Placebo Toothpaste (0ppmF)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.