Experimental Dentifrice Remineralization/Fluoride Uptake in an in Situ Model

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00752089
• Collaborator: (none)
• Enrollment: 20
• Arms: 4
• Duration (Months): 4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether an experimental fluoridated dentifrice is effective in the treatment of dental caries

Condition or Disease	Intervention/Treatment	Phase
Dental Erosion	Drug: NaF/ KNO3/isopentane Dentifrice; Drug: NaF/KNO3 Dentifrice; Drug: NaF Dentifrice; Other: Placebo Dentifrice	Phase 2

Detailed Description

Topical fluorides have been proven to be clinically effective in the prevention of dental caries. It is generally agreed that anti-caries effect of fluoride (F) is mainly by decreasing the rate of enamel demineralization and enhancing the rate of enamel remineralization. An in-situ Surface Micro-hardness (SMH) test is widely used to evaluate enamel demineralization and remineralization during the caries process. Determination of fluoride uptake in-situ also provides better estimation of true fluoride bioavailability of fluoride dentifrice products. In this study, an in-situ remineralization fluoride uptake model will be used to compare the efficacy of experimental dentifrice with a marketed dentifrice and placebo dentifrice. Participants wore partial dentures containing two partially demineralized enamel specimens for two weeks- 24 hours per day, except when brushing (twice daily) with test dentifrice. Following each treatment period, the enamel specimens were analyzed for SMH recovery and fluoride uptake through microdrill enamel biopsy technique.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Exploratory Evaluation of an Experimental Fluoride Dentifrice Formulation Using an in Situ Remineralization/Fluoride Uptake Model
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sodium fluoride/potassium nitrate/Isopentane dentifrice Participants to brush their teeth for one timed minute twice daily with a gel to foam dentifrice containing active ingredients: 1450 ppm F as sodium fluoride (NaF) and 5% potassium nitrate (KNO3) and isopentane as an excipient ingredient.	Drug: NaF/ KNO3/isopentane Dentifrice; Experimental toothpaste
Experimental: NaF/KNO3 Dentifrice Participants to brush their teeth for one timed minute twice daily with a gel to foam dentifrice, containing as active ingredients: 1450 ppm NaF and 5% KNO3 but no isopentane.	Drug: NaF/KNO3 Dentifrice; Experimental toothpaste
Active Comparator: NaF Dentifrice Participants to brush their teeth for one timed minute twice daily with a dentifrice containing 1450 ppm F as NaF.	Drug: NaF Dentifrice; Active comparator
Placebo Comparator: Placebo Dentifrice Participants to brush their teeth for one timed minute twice daily with a fluoride free dentifrice (0 ppm F).	Other: Placebo Dentifrice; Placebo comparator

Outcome Measures

Primary Outcome Measures

1. Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens [Baseline to 14 days]

   SMH test was used to assess mineralization status of enamel specimens using a 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 while decrease in the indentation length represents re-hardening of enamel surface. Percent SMHR 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. Adjusted Mean Change From Baseline in Enamel Fluoride Uptake [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 and expressed as ug*F/cm^3. 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:

1. Age: Aged between 18 and 78

2. Fluoride: Currently living in the Indianapolis area which has a fluoridated water supply (1 ppm F) and not taking fluoride supplements for medical reasons

3. Dentures: Currently wearing a removable mandibular partial denture with sufficient room in the posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 x 7 mm). Willing and capable of wearing their removable partial dentures 24 hours per day during the experimental periods

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

5. Salivary flow:Have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate ≥ 0.2 mL/min; gum base stimulated whole saliva flow rate ≥ 0.8 mL/min

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

7. 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

8. General Health: Good general health with (in the opinion of the investigator) no clinically significant and/or relevant abnormalities of medical history or oral examination that could interfere with participant safety during the study period

Exclusion Criteria:

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

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

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

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

5. Clinical Study/Experimental Medication: Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit

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

Contacts and Locations

Locations

No locations specified.

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: NCT00752089
• Other Study ID Numbers: Z3120510
• First Posted: Sep 15, 2008
• Last Update Posted: Dec 8, 2016
• Last Verified: May 1, 2016

• Keywords provided by GlaxoSmithKline: enamel fluoride uptake; erosion; enamel remineralization
• Additional relevant MeSH terms: Tooth Erosion

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 got their teeth cleaned to remove all accessible plaque and calculus, and were provided with a fluoride free dentifrice for maintaining wash-out period and standardizing the oral conditions.

Arm/Group Title	Overall Study
Arm/Group Description	This was a single-center, examiner blind, randomized, controlled, four treatment cross-over study. Participants have used each study product twice per day for two weeks and participated in each of the four treatment periods.
Period Title: Overall Study
STARTED	20
Received NaF/ KNO3/ 2% Isopentane	19
Received NaF/KNO3/ 0% Isopentane	17
Received NaF	18
Received Placebo	18
COMPLETED	14
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Overall Study Participants
Arm/Group Description	All randomized participants who received all four treatments NaF/ KNO3/ 2% isopentane Dentifrice, NaF/KNO3/ 0% isopentane Dentifrice, NaF Dentifrice, and placebo were included in the baseline assessment.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.31 (8.226)
Sex: Female, Male (Count of Participants)
Female	13 65%
Male	7 35%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens
Description	SMH test was used to assess mineralization status of enamel specimens using a 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 while decrease in the indentation length represents re-hardening of enamel surface. Percent SMHR 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 product, had at least one post-baseline efficacy assessments and no major protocol deviations. Missing data was not imputed. Due to drop-outs, there were differences in the "n" per treatment group.

Arm/Group Title	NaF/ KNO3/ 2% Isopentane Dentifrice	NaF/KNO3/ 0% Isopentane Dentifrice	NaF Dentifrice	Placebo Dentifrice
Arm/Group Description	Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice containing active ingredients: 1450 ppm F as NaF and 5% KNO3 and as an excipient ingredient: 2% isopentane.	Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice, containing as active ingredients: 1450 ppm NaF and 5% KNO3 but no isopentane.	Participants brushed their teeth for one timed minute twice daily with a dentifrice containing 1450 ppm F as NaF.	Participants brushed their teeth for one timed minute twice daily with a fluoride free dentifrice (0 ppm F).
Measure Participants	17	17	17	18
Least Squares Mean (95% Confidence Interval) [% SMHR]	39.46 (4.10)	38.31 (4.11)	36.17 (4.10)	17.26 (4.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF/ KNO3/ 2% Isopentane Dentifrice, NaF/KNO3/ 0% Isopentane Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7756
	Comments	No adjustment for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	1.146
	Confidence Interval	(2-Sided) 95%; -6.904 to 9.196
	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/ KNO3/ 2% Isopentane Dentifrice, NaF Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4194
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	3.291
	Confidence Interval	(2-Sided) 95%; -4.840 to 11.421
	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/ KNO3/ 2% Isopentane Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	22.200
	Confidence Interval	(2-Sided) 95%; 14.280 to 30.120
	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/KNO3/ 0% Isopentane Dentifrice, NaF Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5927
	Comments	No adjustment for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	2.145
	Confidence Interval	(2-Sided) 95%; -5.874 to 10.164
	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/KNO3/ 0% Isopentane Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	21.054
	Confidence Interval	(2-Sided) 95%; 13.189 to 28.919
	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 Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustment for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	18.909
	Confidence Interval	(2-Sided) 95%; 11.036 to 26.783
	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	Adjusted Mean Change From Baseline in Enamel Fluoride Uptake
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 and expressed as ug*F/cm^3. 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 product, had at least one post-baseline efficacy assessments and no major protocol deviations. Missing data was not imputed. Due to drop-outs, there were differences in the "n" per treatment group.

Arm/Group Title	NaF/ KNO3/ 2% Isopentane Dentifrice	NaF/ KNO3/ 0% Isopentane Dentifrice	NaF Dentifrice	Placebo Dentifrice
Arm/Group Description	Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice containing active ingredients: 1450 ppm F as NaF and 5% KNO3 and as an excipient ingredient: 2% isopentane.	Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice, containing as active ingredients: 1450 ppm NaF and 5% KNO3 but no isopentane.	Participants brushed their teeth for one timed minute twice daily with a dentifrice containing 1450 ppm F as NaF.	Participants brushed their teeth for one timed minute twice daily with a fluoride free dentifrice (0 ppm F).
Measure Participants	17	17	17	18
Least Squares Mean (95% Confidence Interval) [ug*F/cm^3]	2445.86 (256.55)	2767.30 (257.16)	2518.54 (256.55)	661.18 (252.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF/ KNO3/ 2% Isopentane Dentifrice, NaF/KNO3/ 0% Isopentane Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1990
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-321.438
	Confidence Interval	(2-Sided) 95%; -818.118 to 175.242
	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/ KNO3/ 2% Isopentane Dentifrice, NaF Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7718
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-72.680
	Confidence Interval	() 95%; -574.398 to 429.039
	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/ KNO3/ 2% Isopentane Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	1784.675
	Confidence Interval	() 95%; 1296.044 to 2273.306
	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/KNO3/ 0% Isopentane Dentifrice, NaF Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3164
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included tratment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	248.758
	Confidence Interval	() 95%; -245.962 to 743.478
	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/KNO3/ 0% Isopentane Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period as fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	2106.113
	Confidence Interval	(2-Sided) 95%; 1620.906 to 2591.320
	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 Dentifrice, Placebo Dentifrice
	Comments	Null hypothesis was no difference between treatments. Tests were 2-sided.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments for multiple comparisons were made as the primary comparison was pre-defined.
	Method	ANOVA
	Comments	The model included treatment and period and fixed and participant as random factors.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	1857.355
	Confidence Interval	(2-Sided) 95%; 1371.637 to 2343.072
	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	Up to 13 weeks
Arm/Group Title	NaF/ KNO3/ 2 % Isopentane Dentifrice		NaF/KNO3/ 0% Isopentane Dentifrice		NaF Dentifrice		Placebo Dentifrice
Arm/Group Description	Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice containing active ingredients: 1450 ppm F as NaF and 5% KNO3 and as an excipient ingredient: 2% isopentane.		Participants brushed their teeth for one timed minute twice daily with a gel to foam dentifrice, containing as active ingredients: 1450 ppm NaF and 5% KNO3 but no isopentane.		Participants brushed their teeth for one timed minute twice daily with a dentifrice containing 1450 ppm F as NaF.		Participants brushed their teeth for one timed minute twice daily with a fluoride free dentifrice (0 ppm F).
All Cause Mortality
	NaF/ KNO3/ 2 % Isopentane Dentifrice		NaF/KNO3/ 0% Isopentane Dentifrice		NaF Dentifrice		Placebo Dentifrice
	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/ KNO3/ 2 % Isopentane Dentifrice		NaF/KNO3/ 0% Isopentane Dentifrice		NaF Dentifrice		Placebo Dentifrice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	NaF/ KNO3/ 2 % Isopentane Dentifrice		NaF/KNO3/ 0% Isopentane Dentifrice		NaF Dentifrice		Placebo Dentifrice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/17 (11.8%)		3/17 (17.6%)		4/18 (22.2%)		2/18 (11.1%)
Gastrointestinal disorders
Gingival erythema	0/17 (0%)	0	1/17 (5.9%)	2	2/18 (11.1%)	2	0/18 (0%)	0
Gingival ulceration	0/17 (0%)	0	1/17 (5.9%)	1	1/18 (5.6%)	1	0/18 (0%)	0
Food poisoning	0/17 (0%)	0	0/17 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Tongue coated	0/17 (0%)	0	0/17 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Infections and infestations
Localised infection	1/17 (5.9%)	1	0/17 (0%)	0	0/18 (0%)	0	0/18 (0%)	0
Nasopharyngitis	0/17 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0	0/18 (0%)	0
Tooth infection	1/17 (5.9%)	1	0/17 (0%)	0	0/18 (0%)	0	0/18 (0%)	0
Injury, poisoning and procedural complications
Tooth fracture	0/17 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.