In Situ Caries Efficacy of Fluoride Toothpastes

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00708097
• Collaborator: (none)
• Enrollment: 57
• Location: 1
• Arms: 5
• Duration (Months): 3
• Patients Per Site Per Month: 19.1

Study Details

Study Description

Brief Summary

This study is to evaluate the effect of fluoride dentifrices on enamel with artificial caries lesions in an in situ model

Condition or Disease	Intervention/Treatment	Phase
Caries	Drug: NaF; Drug: Placebo; Drug: NaMFP	Phase 3

Detailed Description

In situ models represent an acceptable approach for testing the anti-caries potential of fluoride products. This study is to evaluate the effect of fluoride dentifrice containing 1450 parts per million fluoride (ppm F) on enamel with artificial caries lesions in an in situ model. The study toothpaste containing sodium fluoride (NaF) and 0.4% carbopol will be compared to 4 other dentifrices. Comparator toothpastes include NaF toothpaste (1400 ppm F), NaF toothpaste (675 ppm F), sodium monofluorophosphate (NaMFP) and NaF toothpaste (1450 ppm

1. and placebo toothpaste (0 ppm F).

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Efficacy of Fluoride Toothpastes Using an in Situ Caries Model
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NaF toothpaste(1450 ppmF) Study toothpaste containing 1450 ppm F as NaF and 0.4% carbopol as excipient.	Drug: NaF; Fluoride; Other Names: Fluoride
Active Comparator: NaF toothpaste (1400 ppmF) Study toothpaste containing 1400 ppm F as NaF	Drug: NaF; Fluoride; Other Names: Fluoride
Active Comparator: NaMFP/NaF toothpaste (1450 ppmF) Reference toothpaste containing 1000 ppm F as NaMFP and 450 ppm F as NaF	Drug: NaF; Fluoride; Other Names: Fluoride ; Drug: NaMFP; Fluoride
Active Comparator: NaF toothpaste (675 ppmF) Study toothpaste containing 675 ppm F as NaF	Drug: NaF; Fluoride; Other Names: Fluoride
Placebo Comparator: Placebo toothpaste (0 ppmF) Fluoride free placebo toothpaste (0 ppm F)	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage Surface Microhardness Recovery (%SMHR) of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and NaF Toothpaste (1400ppmF) [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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.

Secondary Outcome Measures

1. Percentage SMHR of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF) and Placebo Toothpaste (0ppmF) [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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.

2. Percentage SMHR of Demineralized Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste(1450ppmF) and Placebo Toothpaste (0ppmF) [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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.

3. Enamel Fluoride Uptake (Sound Enamel Specimens) [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.

4. Enamel Fluoride Uptake (Demineralized Specimens) [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 78 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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.

• Age:Aged between 18 and 80 years.

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

• General Health:Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination.

• Fluoride:Currently living in the Indianapolis, Indiana area and not taking fluoride supplements for medical reasons

• Dentures: a)Currently wearing a removable mandibular partial denture with sufficient room in both posterior buccal flange areas to accommodate two enamel specimens on each side, four specimens in total - required dimensions 12 x 7 millimeter (mm) per side.

1. Willing to have their denture modified to accommodate enamel test specimens and willing and capable of wearing their removable mandibular partial dentures 24 hours per day during the experimental periods

• Dental health: Have no current active caries or periodontal disease that may compromise the study or the health of the subjects and all restorations in a good state of repair

• Salivary flow:Have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate = 0.2 milliliter (mL)/minute; gum base stimulated whole saliva flow rate = 0.8 mL/minute)

Exclusion Criteria:

• Pregnancy: Women who are known to be pregnant or who are intending to become pregnant over the duration of the study.

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

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

• Antibiotics: Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit

• Clinical Study/Experimental Medication: a) Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit.b) Participation in another GSKCH investigational dental product study within 7 days of first study treatment c)Previous participation in this study.

• Substance abuse: Recent history (within the last year) of alcohol or other substance abuse.

• Personnel:a) A member of the site study staff living in same household.b)An employee of the sponsor. c) Any employee of any toothpaste manufacturer or their spouse or family member

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: NCT00708097
• Other Study ID Numbers: T3508565
• First Posted: Jul 2, 2008
• Last Update Posted: Jan 1, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by GlaxoSmithKline: fluoride; in situ; remineralization; enamel; caries
• Additional relevant MeSH terms: Fluorides

Study Results

Participant Flow

Pre-assignment Detail	Two days before the start of each treatment period, participants received a professional dental cleaning of their natural teeth, then brushed at home with the fluoride-free toothpaste.

Arm/Group Title	Sodium Fluoride (NaF) Toothpaste(1450 Parts Per Million(Ppm)F)	NaF Toothpaste (1400ppmF)	Sodium Monofluorophosphate (NaMFP)/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 milliliters (mL) water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Period Title: Period 1
STARTED	11	12	12	11	11
COMPLETED	11	11	12	9	10
NOT COMPLETED	0	1	0	2	1
Period Title: Period 1
STARTED	10	12	10	11	10
COMPLETED	10	11	9	10	10
NOT COMPLETED	0	1	1	1	0
Period Title: Period 1
STARTED	9	11	10	10	10
COMPLETED	9	11	10	10	10
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	12	9	10	11	8
COMPLETED	12	9	10	11	8
NOT COMPLETED	0	0	0	0	0
Period Title: Period 1
STARTED	8	9	11	10	12
COMPLETED	8	9	11	10	12
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Randomized Participants
Arm/Group Description	All randomized participants who received at least one of the treatment dentifrices during the study and had at least one safety assessment after using the treatment dentifrice.
Overall Participants	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (10.32)
Sex: Female, Male (Count of Participants)
Female	34 59.6%
Male	23 40.4%
Region of Enrollment (participants) [Number]
United States	57 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Surface Microhardness Recovery (%SMHR) of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and NaF Toothpaste (1400ppmF)
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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop outs there were differences in the number of participants (N) per treatment group.

Arm/Group Title	NaF Toothpaste (1450ppmF)	NaF Toothpaste (1400ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	50	52
Least Squares Mean (Standard Error) [Percentage SMHR]	28.31 (5.54)	26.32 (5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.5757
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.98
	Confidence Interval	(2-Sided) 95%; -5.00 to 8.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

2. Secondary Outcome

Title	Percentage SMHR of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF) and Placebo Toothpaste (0ppmF)
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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

ITT population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there were differences in the number of participants analyzed per treatment group.

Arm/Group Title	NaF/Carbopol Toothpaste(1450ppmF)	NaF Toothpaste(1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	50	52	53	53	51
Least Squares Mean (Standard Error) [Percentage SMHR]	28.31 (5.54)	26.32 (5.51)	26.13 (5.49)	25.52 (5.48)	53.38 (5.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.5387
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	2.17
	Confidence Interval	(2-Sided) 95%; -4.79 to 9.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative 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 of the treatments in comparison, to be equal with respect to percent SMH. 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	0.4306
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	2.79
	Confidence Interval	(2-Sided) 95%; -4.18 to 9.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-25.07
	Confidence Interval	(2-Sided) 95%; -32.09 to -18.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.9567
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -6.71 to 7.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.8188
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; -6.14 to 7.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-27.06
	Confidence Interval	(2-Sided) 95%; -34.03 to -20.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.8599
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; -6.28 to 7.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-27.25
	Confidence Interval	(2-Sided) 95%; -34.20 to -20.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (675ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-27.87
	Confidence Interval	(2-Sided) 95%; -34.84 to -20.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

3. Secondary Outcome

Title	Percentage SMHR of Demineralized Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste(1450ppmF) and Placebo Toothpaste (0ppmF)
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 SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

ITT population. All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there were differences in the number of participants analyzed per treatment group.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste(1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	50	52	53	53	51
Least Squares Mean (Standard Error) [Percentage SMHR]	34.62 (2.82)	36.06 (2.79)	31.12 (2.77)	27.15 (2.77)	11.10 (2.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.5451
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.45
	Confidence Interval	(2-Sided) 95%; -6.15 to 3.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.1433
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	3.50
	Confidence Interval	(2-Sided) 95%; -1.20 to 8.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative 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 of the treatments in comparison, to be equal with respect to percent SMH. 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	0.0020
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	7.47
	Confidence Interval	(2-Sided) 95%; 2.78 to 12.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	23.52
	Confidence Interval	(2-Sided) 95%; 18.79 to 28.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.0373
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	4.94
	Confidence Interval	(2-Sided) 95%; 0.29 to 9.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.0002
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	8.92
	Confidence Interval	(2-Sided) 95%; 4.24 to 13.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	24.97
	Confidence Interval	(2-Sided) 95%; 20.27 to 29.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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	0.0925
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	3.98
	Confidence Interval	(2-Sided) 95%; -0.66 to 8.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	20.03
	Confidence Interval	(2-Sided) 95%; 15.35 to 24.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (675ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	16.05
	Confidence Interval	(2-Sided) 95%; 11.36 to 20.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment.

4. Secondary Outcome

Title	Enamel Fluoride Uptake (Sound Enamel Specimens)
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

ITT population:. All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there are differences in the number of participants analyzed per treatment group.

Arm/Group Title	NaF Toothpaste (1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/ NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	50	52	53	53	51
Least Squares Mean (Standard Error) [micrograms (μg)*F/centimeters(cm)^2]]	648.06 (47.10)	650.07 (46.30)	541.16 (45.91)	487.14 (45.86)	425.59 (46.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.9697
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-2.01
	Confidence Interval	(2-Sided) 95%; -106.34 to 102.32
	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), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0440
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	106.90
	Confidence Interval	(2-Sided) 95%; 2.92 to 210.87
	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 of the treatments in comparison, to be equal with respect to EFU. 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	0.0026
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	160.92
	Confidence Interval	(2-Sided) 95%; 56.96 to 264.88
	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 (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	222.47
	Confidence Interval	(2-Sided) 95%; 117.58 to 327.36
	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 5

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0382
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	108.91
	Confidence Interval	(2-Sided) 95%; 5.98 to 211.83
	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	NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0021
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	162.93
	Confidence Interval	(2-Sided) 95%; 59.68 to 266.18
	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 7

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	224.48
	Confidence Interval	(2-Sided) 95%; 120.51 to 328.46
	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 8

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.3003
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	54.03
	Confidence Interval	(2-Sided) 95%; -48.56 to 156.61
	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 9

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (675ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.2432
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	61.55
	Confidence Interval	(2-Sided) 95%; -42.14 to 165.24
	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 10

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0289
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	115.58
	Confidence Interval	(2-Sided) 95%; 12.02 to 219.13
	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	Enamel Fluoride Uptake (Demineralized Specimens)
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

ITT population: All randomized participants with at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there are differences in the number of participants analyzed per treatment group.

Arm/Group Title	NaF Toothpaste(1450ppmF)	NaF Toothpaste (1400ppmF)	NaMFP/NaF Toothpaste (1450ppmF)	NaF Toothpaste (675ppmF)	Placebo Toothpaste (0ppmF)
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.	Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.
Measure Participants	50	52	53	53	51
Least Squares Mean (Standard Error) [μg*F/cm^2]	2499.47 (133.46)	2513.37 (131.09)	1923.76 (129.91)	1861.80 (129.78)	686.18 (132.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.9293
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-13.90
	Confidence Interval	(2-Sided) 95%; -322.47 to 294.66
	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), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0003
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	575.71
	Confidence Interval	(2-Sided) 95%; 268.24 to 883.17
	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 3

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	637.67
	Confidence Interval	(2-Sided) 95%; 330.30 to 945.03
	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 (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1813.29
	Confidence Interval	(2-Sided) 95%; 1503.03 to 2123.54
	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 (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.0002
	Comments
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	589.61
	Confidence Interval	(2-Sided) 95%; 285.31 to 893.92
	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	NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	651.57
	Confidence Interval	(2-Sided) 95%; 346.44 to 956.70
	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 7

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (1400ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1827.19
	Confidence Interval	(2-Sided) 95%; 1519.78 to 2134.60
	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 8

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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	0.6874
	Comments	No adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	61.96
	Confidence Interval	(2-Sided) 95%; -241.25 to 365.17
	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 9

Statistical Analysis Overview	Comparison Group Selection	NaMFP/NaF Toothpaste (1450ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1237.58
	Confidence Interval	(2-Sided) 95%; 931.46 to 1543.70
	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 10

Statistical Analysis Overview	Comparison Group Selection	NaF Toothpaste (675ppmF), Placebo Toothpaste (0ppmF)
	Comments	Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. 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 adjustment made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment and period with subject as a random effect.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1175.62
	Confidence Interval	(2-Sided) 95%; 869.15 to 1482.10
	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.

Adverse Events

Time Frame	All AEs 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)		NaF Toothpaste (675ppmF)		Placebo Toothpaste (0ppmF)		Overall
Arm/Group Description	Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures.		All participants received all treatments during the study
All Cause Mortality
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		NaF Toothpaste (675ppmF)		Placebo Toothpaste (0ppmF)		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		NaF Toothpaste (675ppmF)		Placebo Toothpaste (0ppmF)		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/52 (0%)		0/53 (0%)		0/53 (0%)		0/51 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	NaF Toothpaste(1450ppmF)		NaF Toothpaste (1400ppmF)		NaMFP/NaF Toothpaste (1450ppmF)		NaF Toothpaste (675ppmF)		Placebo Toothpaste (0ppmF)		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/50 (6%)		1/52 (1.9%)		3/53 (5.7%)		4/53 (7.5%)		1/51 (2%)		10/57 (17.5%)
Gastrointestinal disorders
Gingival erythema	3/50 (6%)	3	1/52 (1.9%)	1	3/53 (5.7%)	3	4/53 (7.5%)	4	1/51 (2%)	1	10/57 (17.5%)	12

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.