Evaluation of Oral Hygiene Products in an In Situ Caries Model

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02399163
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 4
• Duration (Months): 4
• Patients Per Site Per Month: 20

Study Details

Study Description

Brief Summary

The study will evaluate and compare the potential anti-caries efficacy of a test regimen:

placebo (fluoride free) toothpaste (twice daily use) plus fluoride mouthwash (once daily use), in comparison with brushing with a placebo toothpaste alone (twice daily use), to remineralize previously demineralized enamel specimens, as measured by Surface MicroHardness Recovery (%SMHR).

This will be a single center, randomized, laboratory analyst blinded, placebo, four treatment, cross-over study in healthy participants. Participants will be assessed at baseline and at the beginning and end of each treatment visit to monitor clinical efficacy and safety.

Condition or Disease	Intervention/Treatment	Phase
Dental Caries	Drug: Fluoride free toothpaste; Drug: Fluoride toothpaste; Drug: Fluoride mouthwash	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of Oral Hygiene Products in an In Situ Caries Model
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo dentifrice/Fluoride rinse Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride	Drug: Fluoride free toothpaste; Brushing with fluoride free toothpaste; Drug: Fluoride mouthwash; Fluoride mouth wash to be followed after brushing with fluoride free toothpaste in "Placebo dentifrice/Fluoride rinse" arm and in "Fluoride dentifrice/Fluoride rinse" arm
Placebo Comparator: Placebo dentifrice/No rinse Twice daily brushing with a non-fluoride (placebo) toothpaste	Drug: Fluoride free toothpaste; Brushing with fluoride free toothpaste
Active Comparator: Fluoride dentifrice/No rinse Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride	Drug: Fluoride toothpaste; Brushing with fluoride containing toothpaste
Experimental: Fluoride dentifrice/Fluoride rinse Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride.	Drug: Fluoride toothpaste; Brushing with fluoride containing toothpaste; Drug: Fluoride mouthwash; Fluoride mouth wash to be followed after brushing with fluoride free toothpaste in "Placebo dentifrice/Fluoride rinse" arm and in "Fluoride dentifrice/Fluoride rinse" arm

Outcome Measures

Primary Outcome Measures

1. Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse [Baseline to 14 days]

   SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer [μm]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): [D1-R/D1-B]*100.

Secondary Outcome Measures

1. Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse [Baseline to 14 days]

   SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer [μm]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): [D1-R/D1-B]*100.

2. Enamel Fluoride Uptake [Baseline to 14 days]

   The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 micrometer (μm) through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram per square centimeter (μg/cm^2).

3. Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 [Baseline to Day14]

   Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 baseline prior to supervised treatment. - at day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.

4. Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 [Baseline up to Day 14]

   Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Aged between 18 and 85 years inclusive

2. Understands and is willing, able and likely to comply with all study procedures and restrictions

3. Good general and mental health with, in the opinion of the investigator or medically qualified designee:

• No clinically significant and relevant abnormalities in medical history or upon oral examination.

• Absence of any condition that could affect the participant's safety or well-being or their ability to understand and follow study procedures and requirements

1. Currently living in the Indianapolis, Indiana area and has not had a professional fluoride treatment within 14 days of the first treatment visit

2. Currently wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange areas to accommodate two enamel specimens

3. 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

4. Have a salivary flow rate in the range of normal values (un-stimulated whole saliva flow rate ≥ 0.2 milliliter (mL)/minute; gum base stimulated whole saliva flow rate ≥ 0.8 mL/minute).

Exclusion Criteria:

1. Pregnant or breast feeding women

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

3. Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit.

4. Taking or have taken a bisphosphonate drug for treatment of osteoporosis.

5. Participation in another GSKCH investigational dental product study within seven days of first study treatment.

6. Previous participation in this study.

7. Recent history (within the last year) of alcohol or other substance abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	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: NCT02399163
• Other Study ID Numbers: 203160
• First Posted: Mar 26, 2015
• Last Update Posted: May 12, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Dental Caries; Fluorides

Study Results

Participant Flow

Recruitment Details	Participants were recruited at one center in United States of America.
Pre-assignment Detail	A total of 80 participants were screened. Of the 80 participants, 62 were randomized and 53 completed the study.

Arm/Group Title	Overall Study
Arm/Group Description	In this cross-over study, participants were randomized to receive each of following treatments: Fluoride dentifrice/Fluoride rinse Placebo dentifrice/Fluoride rinse Fluoride dentifrice/No rinse Placebo dentifrice/No rinse
Period Title: Overall Study
STARTED	62
COMPLETED	53
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Overall Participants
Arm/Group Description	All randomized participants were evaluated for baseline characteristics
Overall Participants	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.1 (10.45)
Sex: Female, Male (Count of Participants)
Female	35 56.5%
Male	27 43.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	30 48.4%
White	30 48.4%
More than one race	2 3.2%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse
Description	SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer [μm]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): [D1-R/D1-B]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse	Placebo Dentifrice/No Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 parts per million (ppm) of fluoride as sodium fluoride	Twice daily brushing with a non-fluoride (placebo) toothpaste
Measure Participants	53	52
Mean (Standard Deviation) [% SMHR]	24.48 (16.088)	8.09 (25.892)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	From ANOVA: participant (random), treatment (fixed), period (fixed)
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	16.76
	Confidence Interval	(2-Sided) 95%; 11.061 to 22.454
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is Placebo dentifrice/Fluoride rinse minus Placebo dentifrice/No rinse such that a positive difference implies a larger response value for the Placebo dentifrice/Fluoride rinse.

2. Secondary Outcome

Title	Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse
Description	SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer [μm]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): [D1-R/D1-B]*100.
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse	Placebo Dentifrice/No Rinse	Fluoride Dentifrice/No Rinse	Fluoride Dentifrice/Fluoride Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride	Twice daily brushing with a non-fluoride (placebo) toothpaste	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride.
Measure Participants	53	52	54	52
Mean (Standard Deviation) [% SMHR]	24.48 (16.088)	8.09 (25.892)	28.36 (21.037)	30.01 (18.203)

3. Secondary Outcome

Title	Enamel Fluoride Uptake
Description	The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 micrometer (μm) through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram per square centimeter (μg/cm^2).
Time Frame	Baseline to 14 days

Outcome Measure Data

Analysis Population Description

PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse	Placebo Dentifrice/No Rinse	Fluoride Dentifrice/No Rinse	Fluoride Dentifrice/Fluoride Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride	Twice daily brushing with a non-fluoride (placebo) toothpaste	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride.
Measure Participants	53	52	54	52
Mean (Standard Deviation) [microgram per square centimeter(μg/cm^2)]	7.22 (3.016)	1.60 (0.670)	8.01 (3.925)	9.97 (4.962)

4. Secondary Outcome

Title	Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14
Description	Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 baseline prior to supervised treatment. - at day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.
Time Frame	Baseline to Day14

Outcome Measure Data

Analysis Population Description

PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse	Placebo Dentifrice/No Rinse	Fluoride Dentifrice/No Rinse	Fluoride Dentifrice/Fluoride Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride	Twice daily brushing with a non-fluoride (placebo) toothpaste	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride.
Measure Participants	53	51	54	52
Mean (Standard Deviation) [microgram per mililitre(μg/mL )]	0.06 (0.317)	-0.01 (0.030)	0.00 (0.245)	0.06 (0.203)

5. Secondary Outcome

Title	Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14
Description	Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.
Time Frame	Baseline up to Day 14

Outcome Measure Data

Analysis Population Description

PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse	Placebo Dentifrice/No Rinse	Fluoride Dentifrice/No Rinse	Fluoride Dentifrice/Fluoride Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride	Twice daily brushing with a non-fluoride (placebo) toothpaste	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride	Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride
Measure Participants	53	51	54	52
Mean (Standard Deviation) [μg/mL]	13.08 (9.743)	0.05 (0.045)	8.62 (6.892)	13.81 (10.620)

Adverse Events

Arm/Group Title	Placebo Dentifrice/Fluoride Rinse		Placebo Dentifrice/No Rinse		Fluoride Dentifrice/No Rinse		Fluoride Dentifrice/Fluoride Rinse
Arm/Group Description	Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride		Twice daily brushing with a non-fluoride (placebo) toothpaste		Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride		Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride.
All Cause Mortality
	Placebo Dentifrice/Fluoride Rinse		Placebo Dentifrice/No Rinse		Fluoride Dentifrice/No Rinse		Fluoride Dentifrice/Fluoride Rinse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Dentifrice/Fluoride Rinse		Placebo Dentifrice/No Rinse		Fluoride Dentifrice/No Rinse		Fluoride Dentifrice/Fluoride Rinse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)		1/56 (1.8%)		0/59 (0%)		1/57 (1.8%)
Gastrointestinal disorders
HAEMATEMESIS	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
Vascular disorders
HYPERTENSION	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Dentifrice/Fluoride Rinse		Placebo Dentifrice/No Rinse		Fluoride Dentifrice/No Rinse		Fluoride Dentifrice/Fluoride Rinse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/60 (25%)		13/56 (23.2%)		18/59 (30.5%)		17/57 (29.8%)
Ear and labyrinth disorders
EAR PAIN	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
Gastrointestinal disorders
Glossodynia	0/60 (0%)		2/56 (3.6%)		1/59 (1.7%)		2/57 (3.5%)
Tongue Geographic	0/60 (0%)		0/56 (0%)		0/59 (0%)		2/57 (3.5%)
Dry Mouth	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
Dyspepsia	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
Haematemesis	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
Lip Dry	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
Oral Discomfort	1/60 (1.7%)		4/56 (7.1%)		1/59 (1.7%)		1/57 (1.8%)
Paraesthesia Oral	1/60 (1.7%)		1/56 (1.8%)		0/59 (0%)		1/57 (1.8%)
Tongue Ulceration	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		1/57 (1.8%)
Cheilitis	1/60 (1.7%)		2/56 (3.6%)		1/59 (1.7%)		0/57 (0%)
Diarrhoea	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
Gingival Erythema	2/60 (3.3%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
Gingival Hypertrophy	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
Gingival Oedema	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
Gingival Ulceration	0/60 (0%)		1/56 (1.8%)		1/59 (1.7%)		0/57 (0%)
Lip Ulceration	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
MOUTH HAEMORRHAGE	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
MOUTH ULCERATION	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
ORAL MUCOSAL ERYTHEMA	1/60 (1.7%)		1/56 (1.8%)		1/59 (1.7%)		0/57 (0%)
TRAUMATIC OCCLUSION	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
General disorders
INJURY ASSOCIATED WITH DEVICE	0/60 (0%)		1/56 (1.8%)		2/59 (3.4%)		1/57 (1.8%)
CHEST PAIN	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
MEDICAL DEVICE PAIN	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
NON-CARDIAC CHEST PAIN	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
Infections and infestations
NASOPHARYNGITIS	0/60 (0%)		1/56 (1.8%)		1/59 (1.7%)		1/57 (1.8%)
ORAL HERPES	0/60 (0%)		1/56 (1.8%)		1/59 (1.7%)		1/57 (1.8%)
BRONCHITIS	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
SINUSITIS	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
Injury, poisoning and procedural complications
MOUTH INJURY	2/60 (3.3%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
TONGUE INJURY	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
ARTHROPOD BITE	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
ARTHROPOD STING	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
LACERATION	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
POST PROCEDURAL HAEMORRHAGE	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
TRAUMATIC HAEMATOMA	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
Investigations
SMEAR CERVIX ABNORMAL	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		3/57 (5.3%)
ARTHRALGIA	1/60 (1.7%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
MUSCULOSKELETAL PAIN	0/60 (0%)		0/56 (0%)		1/59 (1.7%)		0/57 (0%)
MYALGIA	0/60 (0%)		1/56 (1.8%)		2/59 (3.4%)		0/57 (0%)
Nervous system disorders
HEADACHE	1/60 (1.7%)		2/56 (3.6%)		1/59 (1.7%)		0/57 (0%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
THROAT TIGHTNESS	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
Skin and subcutaneous tissue disorders
URTICARIA	0/60 (0%)		0/56 (0%)		0/59 (0%)		1/57 (1.8%)
ERYTHEMA	1/60 (1.7%)		1/56 (1.8%)		0/59 (0%)		0/57 (0%)
RASH	1/60 (1.7%)		0/56 (0%)		0/59 (0%)		0/57 (0%)
Vascular disorders
HYPERTENSION	0/60 (0%)		1/56 (1.8%)		0/59 (0%)		0/57 (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.