Evaluation of Efficacy of Experimental Gel to Foam Dentifrices in Dental Erosion

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01657903
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arms: 4
• Duration (Months): 3
• Patients Per Site Per Month: 18.5

Study Details

Study Description

Brief Summary

The purpose of this study is to compare and evaluate the ability of two European Union (EU) regulated gel to foam toothpaste formulations versus a non-fluoride toothpaste using a modified in-situ model of dental erosion and remineralization. A positive control i.e fluoride containing toothpaste marketed in EU will also be compared to non-fluoride toothpaste.

Condition or Disease	Intervention/Treatment	Phase
Dental Erosion; Acid Wear	Drug: Sodium Fluoride; Drug: Potassium nitrate	N/A

Detailed Description

The aim of this study is to assess the remineralization effects of two EU gel to foam toothpaste formulations with 1450 parts per million (ppm) of fluoride as sodium fluoride (NaF) and 5% potassium nitrate (KNO3) versus a non-fluoride (0 ppm F)/KNO3 toothpaste as a negative control. The two experimental gel to foam toothpaste formulations differ in their relative dentine abrasivity (RDA) values which is an in-vitro measure of a toothpaste abrasivity to the dentinal tissues. A marketed toothpaste containing NaF and KNO3 will serve as a positive control.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: A Placebo Controlled Study to Evaluate the Effectiveness of Experimental Foaming Gel Toothpastes Using an In-situ Erosion Remineralization Model
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NaF/KNO3 toothpaste, Low RDA Participants to brush with 1.5 g of low RDA gel to foam toothpaste containing 1450 ppm F - EU level as NaF. All study treatments contain 5% weight by weight (w/w) KNO3.	Drug: Sodium Fluoride; Toothpaste containing 1450 ppm F - EU level as NaF.; Drug: Potassium nitrate; All study treatments contain 5% w/w KNO3.
Experimental: NaF/KNO3 toothpaste, Medium RDA Participants to brush with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F - EU level as NaF. All study treatments contain 5% w/w KNO3.	Drug: Sodium Fluoride; Toothpaste containing 1450 ppm F - EU level as NaF.; Drug: Potassium nitrate; All study treatments contain 5% w/w KNO3.
Active Comparator: NaF/KNO3 toothpaste Participants to brush with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F - EU level as NaF. All study treatments contain 5% w/w KNO3.	Drug: Sodium Fluoride; Toothpaste containing 1450 ppm F - EU level as NaF.; Drug: Potassium nitrate; All study treatments contain 5% w/w KNO3.
Placebo Comparator: No fluoride/KNO3 toothpaste Participants to brush with a fluoride free toothpaste (0 ppmF). All study treatments contain 5% w/w KNO3.	Drug: Potassium nitrate; All study treatments contain 5% w/w KNO3.

Outcome Measures

Primary Outcome Measures

1. Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure [Baseline, 4 hours post treatment in each treatment period]

   Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: [(E1-E2)/ (E1-B)]*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.

2. Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure [Baseline, 4 hours post treatment in each treatment period]

   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 rehardening of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first erosive challenge (E1) using formula: [(E1- R)/ (E1-B)]*100. A higher percentage values indicate a better outcome.

Other Outcome Measures

1. RER of Enamel Specimens Post 2 Hours of Treatment Exposure [Baseline, 2 hours post treatment in each treatment period]

   Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: [(E1-E2)/ (E1-B)]*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.

2. SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure [Baseline, 2 hours post treatment in each treatment period]

   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 rehardening of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first erosive challenge (E1) using formula: [(E1- R)/ (E1-B)]*100. A higher percentage values indicate a better outcome.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• General and Oral Health: Good general health with (in the opinion of the investigator) no clinically OST and OHT examinations.

• Oral Requirements:

• An intact maxillary dental arch suitable for the retention of the palatal appliance and an intact mandibular dental arch. Subjects may have fixed bridges replacing missing teeth.

• A gum base stimulated whole saliva flow rate ≥ 0.8 g/min and an unstimulated whole saliva flow rate ≥ 0.2 g/min.

• Contraception: Women of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.

Exclusion Criteria:

• Oral Health:

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

• Lesions of the oral cavity that could interfere with the study evaluations, including severe gingivitis, grossly carious lesions, periodontitis and other severe periodontal disease.

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

• Clinical Study/Experimental Medication:

• Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit

• Previous participation in this study

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

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

• Breast-feeding: Women who are breast-feeding

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: NCT01657903
• Other Study ID Numbers: Z6961385
• First Posted: Aug 6, 2012
• Last Update Posted: Jan 26, 2015
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Tooth Erosion; Listerine; Fluorides; Sodium Fluoride

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the clinical site.

Arm/Group Title	Overall
Arm/Group Description	This was a 4-way crossover study. Participants brushed with 1.5 g of low relative dentine abrasivity (RDA) gel to foam toothpaste (Toothpaste 1) containing 1450 parts per million (ppm) of fluoride (F) as sodium fluoride (NaF) and 5% weight by weight (w/w) potassium nitrate (KNO3); 1.5 g of medium RDA gel to foam toothpaste (Toothpaste 2) containing 1450 ppm F as NaF and 5% w/w KNO3; 1.5 g of Marketed toothpaste (Toothpaste 3) containing 1450 ppm F as NaF and 5% w/w KNO3; and 1.5 g of placebo toothpaste containing no fluoride but 5% w/w KNO3. There was a washout period of 2 days following each treatment session. In this washout period, participants used a non-fluoridated toothpaste to ensure no carry over effect.
Period Title: Overall Study
STARTED	56
Received Placebo (No NaF/KNO3)Toothpaste	56
Received NaF/KNO3 Toothpaste 1	55
Received NaF/KNO3 Toothpaste 3	54
Received NaF/KNO3 Toothpaste 2	55
COMPLETED	54
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	All Randomized Participants
Arm/Group Description	All randomized participants were evaluated for baseline parameters.
Overall Participants	56
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.7 (13.77)
Sex: Female, Male (Count of Participants)
Female	27 48.2%
Male	29 51.8%

Outcome Measures

1. Primary Outcome

Title	Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure
Description	Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: [(E1-E2)/ (E1-B)]*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.
Time Frame	Baseline, 4 hours post treatment in each treatment period

Outcome Measure Data

Analysis Population Description

Per protocol (PP) population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.

Arm/Group Title	NaF/KNO3 Toothpaste 1	NaF/KNO3 Toothpaste 2	NaF/KNO3 Toothpaste 3	No Fluoride/KNO3 Toothpaste
Arm/Group Description	Participants brushed with 1.5 g of low RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with a fluoride free toothpaste (0 ppmF) containing only 5% w/w KNO3.
Measure Participants	55	54	54	56
Least Squares Mean (Standard Error) [Percentage RER]	-36.66 (2.824)	-36.53 (2.848)	-36.98 (2.847)	-77.82 (2.799)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF/KNO3 Toothpaste 1, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	41.15
	Confidence Interval	(2-Sided) 95%; 34.42 to 47.89
	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 Toothpaste 2, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	41.28
	Confidence Interval	(2-Sided) 95%; 34.51 to 48.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	NaF/KNO3 Toothpaste 3, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	40.83
	Confidence Interval	(2-Sided) 95%; 34.06 to 47.61
	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.

2. Primary Outcome

Title	Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure
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 rehardening of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first erosive challenge (E1) using formula: [(E1- R)/ (E1-B)]*100. A higher percentage values indicate a better outcome.
Time Frame	Baseline, 4 hours post treatment in each treatment period

Outcome Measure Data

Analysis Population Description

PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.

Arm/Group Title	NaF/KNO3 Toothpaste 1	NaF/KNO3 Toothpaste 2	NaF/KNO3 Toothpaste 3	No Fluoride/KNO3 Toothpaste
Arm/Group Description	Participants brushed with 1.5 g of low RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with a fluoride free toothpaste (0 ppm F) containing only 5% w/w KNO3.
Measure Participants	55	54	54	56
Least Squares Mean (Standard Error) [Percentage SMH]	32.24 (1.469)	32.32 (1.480)	34.53 (1.480)	22.87 (1.457)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NaF/KNO3 Toothpaste 1, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	9.36
	Confidence Interval	(2-Sided) 95%; 6.01 to 12.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NaF/KNO3 Toothpaste 2, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	9.45
	Confidence Interval	(2-Sided) 95%; 6.07 to 12.82
	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 Toothpaste 3, No Fluoride/KNO3 Toothpaste
	Comments	Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	No adjustments made for multiple comparisons as the primary comparison was pre-specified.
	Method	ANOVA
	Comments	ANOVA with factors for treatment, study period, and subject (random effect).
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	11.66
	Confidence Interval	(2-Sided) 95%; 8.28 to 15.03
	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.

3. Other Pre-specified Outcome

Title	RER of Enamel Specimens Post 2 Hours of Treatment Exposure
Description	Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: [(E1-E2)/ (E1-B)]*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.
Time Frame	Baseline, 2 hours post treatment in each treatment period

Outcome Measure Data

Analysis Population Description

PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.

Arm/Group Title	NaF/KNO3 Toothpaste 1	NaF/KNO3 Toothpaste 2	NaF/KNO3 Toothpaste 3	No Fluoride/KNO3 Toothpaste
Arm/Group Description	Participants brushed with 1.5 g of low RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with a fluoride free toothpaste (0 ppmF) containing only 5% w/w KNO3.
Measure Participants	55	54	54	56
Least Squares Mean (Standard Error) [% RER]	-43.76 (3.182)	-43.33 (3.211)	-41.88 (3.210)	-85.88 (3.154)

4. Other Pre-specified Outcome

Title	SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure
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 rehardening of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first erosive challenge (E1) using formula: [(E1- R)/ (E1-B)]*100. A higher percentage values indicate a better outcome.
Time Frame	Baseline, 2 hours post treatment in each treatment period

Outcome Measure Data

Analysis Population Description

PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis.

Arm/Group Title	NaF/KNO3 Toothpaste 1	NaF/KNO3 Toothpaste 2	NaF/KNO3 Toothpaste 3	No Fluoride/KNO3 Toothpaste
Arm/Group Description	Participants brushed with 1.5 g of low RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.	Participants brushed with a fluoride free toothpaste (0 ppm F) containing only 5% w/w KNO3.
Measure Participants	55	54	54	56
Least Squares Mean (Standard Error) [Percentage SMH]	28.96 (1.600)	28.92 (1.615)	28.30 (1.615)	17.90 (1.585)

Adverse Events

Time Frame	All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
Arm/Group Title	NaF/KNO3 Toothpaste 1		NaF/KNO3 Toothpaste 2		NaF/KNO3 Toothpaste 3		No Fluoride/KNO3 Toothpaste
Arm/Group Description	Participants brushed with 1.5 g of low RDA gel to foam toothpaste containing 1450 parts per million of fluoride as NaF and 5% w/w KNO3.		Participants brushed with 1.5 g of medium RDA gel to foam toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.		Participants brushed with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F as NaF and 5% w/w KNO3.		Participants brushed with a fluoride free toothpaste (0 ppmF) containing only 5% w/w KNO3.
All Cause Mortality
	NaF/KNO3 Toothpaste 1		NaF/KNO3 Toothpaste 2		NaF/KNO3 Toothpaste 3		No Fluoride/KNO3 Toothpaste
	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 Toothpaste 1		NaF/KNO3 Toothpaste 2		NaF/KNO3 Toothpaste 3		No Fluoride/KNO3 Toothpaste
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/55 (0%)		0/54 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	NaF/KNO3 Toothpaste 1		NaF/KNO3 Toothpaste 2		NaF/KNO3 Toothpaste 3		No Fluoride/KNO3 Toothpaste
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/55 (3.6%)		0/55 (0%)		1/54 (1.9%)		2/56 (3.6%)
Gastrointestinal disorders
Gingival Pain	1/55 (1.8%)	1	0/55 (0%)	0	0/54 (0%)	0	0/56 (0%)	0
Infections and infestations
Nasopharyngitis	0/55 (0%)	0	0/55 (0%)	0	1/54 (1.9%)	1	2/56 (3.6%)	2
Musculoskeletal and connective tissue disorders
Back Pain	1/55 (1.8%)	1	0/55 (0%)	0	0/54 (0%)	0	0/56 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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