Enamel Remineralization Potential of Dentifrices in Situ

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01128946
• Collaborator: (none)
• Enrollment: 83
• Location: 1
• Arms: 4
• Duration (Months): 3.9
• Patients Per Site Per Month: 21.1

Study Details

Study Description

Brief Summary

This study will use an oral in-situ caries model to study remineralization of enamel due to the action of different combinations of fluoride salts delivered from dentifrices.

Condition or Disease	Intervention/Treatment	Phase
Dental Caries	Drug: NaF; Drug: SnF; Drug: NaMFP	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Comparison of Enamel Remineralization Potential of Dentifrices Incorporating Different Fluoride Salts Using an in Situ Caries Model
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluoride Toothpaste 1 Fluoride toothpaste containing sodium fluoride (NaF)	Drug: NaF; Fluoride toothpaste containing sodium fluoride as 1450 parts per million (ppm) F, 675 ppmF, 450 ppmF, 350ppmF.
Experimental: Fluoride Toothpaste 2 Fluoride toothpaste containing stannous fluoride (SnF) and NaF.	Drug: NaF; Fluoride toothpaste containing sodium fluoride as 1450 parts per million (ppm) F, 675 ppmF, 450 ppmF, 350ppmF.; Drug: SnF; Fluoride toothpaste containing stannous fluoride (1100 ppmF)
Experimental: Fluoride Toothpaste 3 Fluoride toothpaste containing sodium monofluorophosphate (NaMFP) and NaF.	Drug: NaF; Fluoride toothpaste containing sodium fluoride as 1450 parts per million (ppm) F, 675 ppmF, 450 ppmF, 350ppmF.; Drug: NaMFP; Fluoride toothpaste containing sodium monofluorophosphate (1000 ppmF)
Active Comparator: Reference Dentifrice Low fluoride toothpaste containing NaF	Drug: NaF; Fluoride toothpaste containing sodium fluoride as 1450 parts per million (ppm) F, 675 ppmF, 450 ppmF, 350ppmF.

Outcome Measures

Primary Outcome Measures

1. Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF) [Baseline to 14 days]

   SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: [(D-R)/(D-B)]*100.

Secondary Outcome Measures

1. %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) [Baseline to 14 days]

   SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: [(D-R)/ (D-B)]*100.

2. Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) [Baseline to 14 days]

   Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical or oral health.

• No current active caries or periodontal disease that may compromise the study or health of the subject.

• All restorations in a good state of repair

• Currently wearing a removable mandibular partial denture with sufficient room in the posterior buccal flange area to accomodate two enamel specimens required dimensions 12 x 7 mm.

• Willing to have their denture modified to accomodate enamel test specimens

• Willing and capable of wearing removable mandibular partial dentures 24 hours per day during the treatment periods.

• Salivary flow rate in the range of normal values (unstimulated whole saliva flow rate greater than or equal to 0.2 mL/ minute; gum base stimulated whole saliva flow rate greater than or equal to 0.8 mL/minute.

Exclusion Criteria:

• Individuals currently taking antibiotics, or who have taken antibiotics within 30 days prior to the first treatment visit.

• Current active caries or periodontal disease that may compromise the study or health of the subject.

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: NCT01128946
• Other Study ID Numbers: T3500690
• First Posted: May 24, 2010
• Last Update Posted: Jan 1, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by GlaxoSmithKline: Enamel remineralization; Fluoride; caries
• Additional relevant MeSH terms: Dental Caries

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the clinical site.
Pre-assignment Detail	Two to three days before the start of each treatment period, participants received a professional dental cleaning of their natural teeth, then brushed with the study wash out toothpaste and toothbrush.

Arm/Group Title	Sodium Fluoride (NaF) Toothpaste(1450 Parts Per Million(Ppm)F	Sodium Monofluorophosphate (NaMFP)/NaF Toothpaste (1450ppmF	Strontium Fluoride (SnF)/NaF Toothpaste (1450ppmF	NaF Toothpaste (675ppmF
Arm/Group Description	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 gram (g) NaF toothpaste (1450ppmF as NaF), followed by rinsing with 15 milliliters (mL) water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with 1.5g NaMFP and NaF toothpaste (1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g SnF toothpaste (1100ppmF as SnF and 350ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with NaF toothpaste (675ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Period Title: Period I
STARTED	20	21	21	21
COMPLETED	20	20	20	20
NOT COMPLETED	0	1	1	1
Period Title: Period I
STARTED	20	20	20	20
COMPLETED	20	19	20	19
NOT COMPLETED	0	1	0	1
Period Title: Period I
STARTED	20	19	20	19
COMPLETED	19	19	20	19
NOT COMPLETED	1	0	0	0
Period Title: Period I
STARTED	19	20	19	19
COMPLETED	19	20	19	19
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All randomized participants
Overall Participants	83
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.0 (8.73)
Sex: Female, Male (Count of Participants)
Female	48 57.8%
Male	35 42.2%
Region of Enrollment (Number) [Number]
United States	83 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF)
Description	SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: [(D-R)/(D-B)]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group.

Arm/Group Title	NaF Toothpaste (1450ppmF)	SnF/NaF Toothpaste (1450ppmF)
Arm/Group Description	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g NaF toothpaste (1450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g SnF toothpaste (1100ppmF as SnF and 350ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	78	79
Mean (Standard Error) [Percentage of SMHR]	40.94 (1.930)	17.88 (1.924)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	23.06
	Confidence Interval	(2-Sided) 95%; 19.63 to 26.48
	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	%SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF)
Description	SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: [(D-R)/ (D-B)]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

PP population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group

Arm/Group Title	NaF Toothpaste (1450ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	SnF/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)
Arm/Group Description	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g NaF toothpaste (1450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with 1.5g NaMFP and NaF toothpaste (1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g SnF toothpaste (1100ppmF as SnF and 350ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with NaF toothpaste (675ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	78	78	79	76
Mean (Standard Error) [Percentage]	40.94 (1.93)	30.19 (1.932)	17.88 (1.924)	28.74 (1.943)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	10.75
	Confidence Interval	(2-Sided) 95%; 7.33 to 14.17
	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 (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	12.20
	Confidence Interval	(2-Sided) 95%; 8.74 to 15.67
	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	SnF/NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	12.31
	Confidence Interval	(2-Sided) 95%; 8.90 to 15.72
	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 4

Statistical Analysis Overview	Comparison Group Selection	SnF/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4070
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; -2.00 to 4.91
	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	SnF/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-10.85
	Confidence Interval	(2-Sided) 95%; -14.30 to -7.40
	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 Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF)
Description	Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

PP population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group.

Arm/Group Title	NaF Toothpaste (1450ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	SnF/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)
Arm/Group Description	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g NaF toothpaste (1450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with 1.5g NaMFP and NaF toothpaste (1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g SnF toothpaste (1100ppmF as SnF and 350ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth twice daily, for one timed minute with NaF toothpaste (675ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	78	78	79	76
Mean (Standard Error) [micrograms (μg)*F/centimeters(cm)^2]]	22.23 (0.853)	13.54 (0.854)	9.13 (0.850)	14.31 (0.861)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	13.21
	Confidence Interval	(2-Sided) 95%; 11.46 to 14.96
	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 (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	8.79
	Confidence Interval	(2-Sided) 95%; 7.04 to 10.55
	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 (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	8.03
	Confidence Interval	(2-Sided) 95%; 6.25 to 9.80
	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	SnF/NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	4.41
	Confidence Interval	(2-Sided) 95%; 2.66 to 6.16
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SnF/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3942
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -2.54 to 1.00
	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 6

Statistical Analysis Overview	Comparison Group Selection	SnF/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-5.18
	Confidence Interval	(2-Sided) 95%; -6.95 to -3.41
	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 (675ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		SnF/NaF Toothpaste (1450ppmF)
Arm/Group Description	Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g NaF toothpaste (1450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth twice daily, for one timed minute with NaF toothpaste (675ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth twice daily, for one timed minute with 1.5g NaMFP and NaF toothpaste (1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 15 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth twice daily, for one timed minute, with 1.5 g SnF toothpaste (1100ppmF as SnF and 350ppmF as NaF), followed by rinsing with 15mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days with instructions to not brush the enamel specimens. Participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
All Cause Mortality
	NaF Toothpaste (1450ppmF)		NaF Toothpaste (675ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		SnF/NaF Toothpaste (1450ppmF)
	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 (675ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		SnF/NaF Toothpaste (1450ppmF)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/79 (0%)		0/79 (0%)		1/80 (1.3%)		0/80 (0%)
Cardiac disorders
Coronary Artery Disease	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Other (Not Including Serious) Adverse Events
	NaF Toothpaste (1450ppmF)		NaF Toothpaste (675ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		SnF/NaF Toothpaste (1450ppmF)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/79 (12.7%)		12/79 (15.2%)		18/80 (22.5%)		15/80 (18.8%)
Eye disorders
Conjunctivitis	0/79 (0%)	0	1/79 (1.3%)	1	0/80 (0%)	0	0/80 (0%)	0
Gastrointestinal disorders
Bronchitis	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Gingival Erythema	0/79 (0%)	0	1/79 (1.3%)	1	2/80 (2.5%)	2	0/80 (0%)	0
Gingival Ulceration	1/79 (1.3%)	1	1/79 (1.3%)	1	0/80 (0%)	0	1/80 (1.3%)	1
Gingivitis	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	1/80 (1.3%)	1
Lip ulceration	0/79 (0%)	0	2/79 (2.5%)	2	0/80 (0%)	0	0/80 (0%)	0
Mouth Ulceration	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	1/80 (1.3%)	1
Chapped Lips	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Dry Mouth	1/79 (1.3%)	1	0/79 (0%)	0	0/80 (0%)	0	0/80 (0%)	0
Mouth Hemorrhage	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Oral Discomfort	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Tongue Ulceration	0/79 (0%)	0	1/79 (1.3%)	1	0/80 (0%)	0	0/80 (0%)	0
Toothache	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Immune system disorders
Seasonal Allergy	1/79 (1.3%)	1	0/79 (0%)	0	0/80 (0%)	0	0/80 (0%)	0
Infections and infestations
Nasopharyngitis	2/79 (2.5%)	2	1/79 (1.3%)	1	3/80 (3.8%)	3	3/80 (3.8%)	4
Gastrointestinal Viral	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	1/80 (1.3%)	1
Oral Herpes	1/79 (1.3%)	1	1/79 (1.3%)	1	0/80 (0%)	0	0/80 (0%)	0
Sinusitis	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	2/80 (2.5%)	2
Conjunctivitis Infective	0/79 (0%)	0	1/79 (1.3%)	1	0/80 (0%)	0	0/80 (0%)	0
Influenza	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Urinary Tract Infection	1/79 (1.3%)	1	0/79 (0%)	0	0/80 (0%)	0	0/80 (0%)	0
Vaginitis Bacterial	1/79 (1.3%)	1	0/79 (0%)	0	0/80 (0%)	0	0/80 (0%)	0
Injury, poisoning and procedural complications
Mouth Injury	2/79 (2.5%)	2	3/79 (3.8%)	4	1/80 (1.3%)	2	3/80 (3.8%)	3
Thermal Burn	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	2	0/80 (0%)	0
Tongue Injury	1/79 (1.3%)	1	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Ankle Fracture	0/79 (0%)	0	1/79 (1.3%)	1	0/80 (0%)	0	0/80 (0%)	0
Incision Site Pain	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Metabolism and nutrition disorders
Diabetes Mellitus	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Musculoskeletal and connective tissue disorders
Arthritis	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Back Pain	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Coccydynia	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Nervous system disorders
Burning Sensation	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Headache	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Nerve Compression	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	0/79 (0%)	0	0/79 (0%)	0	0/80 (0%)	0	1/80 (1.3%)	1
Vascular disorders
Hypertension	0/79 (0%)	0	0/79 (0%)	0	1/80 (1.3%)	1	0/80 (0%)	0

Limitations/Caveats

[Not Specified]

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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.