Clinical Study to Evaluate the Efficacy of Two Dentifrices for Dentine Hypersensitivity

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02371616
• Collaborator: (none)
• Enrollment: 304
• Locations: 3
• Arms: 2
• Actual Duration (Months): 2.6
• Patients Per Site: 101.3
• Patients Per Site Per Month: 38.6

Study Details

Study Description

Brief Summary

An 8 week clinical study to evaluate the ability of an experimental dentifrice containing calcium sodium phosphosilicate and sodium fluoride to provide relief from dentine hypersensitivity compared to a marketed dentifrice containing calcium sodium phosphosilicate and sodium monofluorophosphate.

Condition or Disease	Intervention/Treatment	Phase
Dentine Sensitivity	Device: Calcium sodium phosphosilicate; Other: Sodium fluoride; Other: Sodium monofluorophosphate	N/A

Detailed Description

A single centre, multi-site, randomised, examiner blind, two treatment, parallel group, non-inferiority design clinical study conducted in healthy subjects with self-reported and clinically diagnosed dentine hypersensitivity (DH). This study will compare the effectiveness of a test dentifrice containing 5% w/w calcium sodium phosphosilicate and fluoride as sodium fluoride to a commercially available dentifrice containing 5% w/w calcium sodium phosphosilicate and fluoride as sodium monofluorophosphate, in providing relief from DH after 4 and 8 weeks twice daily treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 304 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Clinical Study to Evaluate the Efficacy of Two Dentifrices for Dentine Hypersensitivity
• Actual Study Start Date: Sep 29, 2014
• Actual Primary Completion Date: Dec 18, 2014
• Actual Study Completion Date: Dec 18, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test dentifrice Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium flouride	Device: Calcium sodium phosphosilicate; 5% w/w calcium sodium phosphosilicate; Other: Sodium fluoride; 1426 ppm fluoride as sodium fluoride
Active Comparator: Comparator dentifrice Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate	Device: Calcium sodium phosphosilicate; 5% w/w calcium sodium phosphosilicate; Other: Sodium monofluorophosphate; 1426 ppm fluoride as sodium monofluorophosphate

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Visual Analogue Score (VAS) at Week 8 [At Baseline and Week 8]

   Evaporative air sensitivity was assessed by examiner as a response to a 1 second application of air from a triple air dental syringe applied to the exposed dentine surface of hypersensitive tooth from a distance of approximately 1centimeter. Each participants rated the intensity of their response to the stimulus using a 100 millimeter (mm) VAS, were 0 represented "no pain" and 100 represented the" worst pain imaginable". Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.

Secondary Outcome Measures

1. Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Visual Analogue Score (VAS) at Week 4 [At Baseline and Week 4]

   Evaporative air sensitivity was assessed by examiner as a response to a 1 second application of air from a triple air dental syringe applied to the exposed dentine surface of hypersensitive tooth from a distance of approximately 1centimeter. Each participants rated the intensity of their response to the stimulus using a 100 mm VAS, were 0 represented "no pain" and 100 represented the" worst pain imaginable". Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.

2. Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Schiff Sensitivity Score at Week 4 and Week 8 [At Baseline, Week 4 and Week 8]

   Evaporative air sensitivity was measured by examiner as the participant's response to an evaporative air stimulus for each tooth using the Schiff Sensitivity Scale scored as follows - 0: Participant does not respond to air stimulation; 1: responds to air stimulus but does not request discontinuation of stimulus; 2: Participant responds to air stimulus and requests discontinuation or moves from stimulus; 3: Participant responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicate improvement in sensitivity. Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.

3. Change From Baseline in Tactile Threshold at Week 4 and Week 8 [At Baseline, Week 4 and Week 8]

   Tactile threshold was assessed by examiner using a constant pressure probe (Yeaple probe) which allowed application of a known force to the dentine surface from 10 g to an upper threshold of 80g in increments of 10 g. The tactile threshold is the maximum pressure applied at which participant do not report any pain or discomfort. The tactile threshold for each tooth was determined by asking the participant whether the sensation caused discomfort. The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold. The higher the tactile threshold, the less sensitive the tooth. Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• subjects in good general health with no clinically significant/ relevant abnormalities of oral examination

• pre-existing self reported and clinically diagnosed tooth sensitivity

• at screening a minimum of 20 natural teeth and at least two accessible, non-adjacent teeth (incisors, canines or pre-molars) with signs of erosion or abrasion and/or facial/cervical gingival recession (EAR), with a Gingival Index ≤1 and clinical mobility ≤1, and with signs of DH as measured by qualifying evaporative (air) assessment

• at baseline, a minimum of 2 non-adjacent accessible teeth (incisors, canines or premolars) with DH (qualifying tactile threshold Yeaple ≤ 20g, Schiff Sensitivity Score ≥ 2)

Exclusion Criteria:

• subjects with a known or suspected intolerance or hypersensitivity to study products

• presence of chronic debilitating disease which could affect study outcomes

• any condition which is causing dry mouth

• use of an oral care product indicated for the relief of dentine hypersensitivity

• participation in a DH treatment study in the 8 weeks prior to screening

• taking daily doses of a medication/ treatment which could interfere with perception of pain or is causing dry mouth

• require antibiotic prophylaxis for dental procedures

• dental prophylaxis within 4 weeks of screening

• treatment of periodontal disease within 12 months of screening+C60

• scaling or root planing within 3 months of screening

• tooth bleaching within 8 weeks of screening

• active caries or periodontitis

• partial dentures, orthodontic appliances or dental implants which could affect study outcomes

• Pregnant and breast-feeding females

• Main Exclusions for Test Teeth: evidence of current or recent caries; treatment of decay within 12 months of screening; teeth with exposed dentine but with deep, defective or facial restorations; teeth used as abutments for fixed or removable partial dentures; teeth with full crowns or veneers, orthodontic bands or cracked enamel; sensitive teeth with contributing aetiologies other than erosion, abrasion or recession

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Ellesmere Port	Cheshire	United Kingdom	CH65 4BW
2	GSK Investigational Site	Maldon	Essex	United Kingdom	CM9 5PN
3	GSK Investigational Site	Wirral		United Kingdom	CH41 6EY

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: NCT02371616
• Other Study ID Numbers: 202199
• First Posted: Feb 25, 2015
• Last Update Posted: Apr 4, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Dentin Sensitivity; Hypersensitivity; Listerine; Calcium; Fluorides; Sodium Fluoride; Fluorophosphate

Study Results

Participant Flow

Recruitment Details	Participants were recruited at one center (three sites) in United Kingdom.
Pre-assignment Detail	A total of 731 participants were screened, out of which 304 participants were randomized. 427 participants were not randomized because 377 did not met the study criteria, 1 had adverse event, 3 were lost to follow up and 1 due to protocol violation, 5 withdrew consent and 40 participants were not randomized because of other reasons (not specified).

Arm/Group Title	Test Dentifrice	Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% weight by weight (w/w) calcium sodium phosphosilicate and 1426 parts per million (ppm) fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
Period Title: Overall Study
STARTED	150	154
COMPLETED	146	147
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	Test Dentifrice	Comparator Dentifrice	Total
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.	Total of all reporting groups
Overall Participants	150	154	304
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (10.33)	42.5 (9.43)	41.9 (9.89)
Sex: Female, Male (Count of Participants)
Female	122 81.3%	131 85.1%	253 83.2%
Male	28 18.7%	23 14.9%	51 16.8%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Visual Analogue Score (VAS) at Week 8
Description	Evaporative air sensitivity was assessed by examiner as a response to a 1 second application of air from a triple air dental syringe applied to the exposed dentine surface of hypersensitive tooth from a distance of approximately 1centimeter. Each participants rated the intensity of their response to the stimulus using a 100 millimeter (mm) VAS, were 0 represented "no pain" and 100 represented the" worst pain imaginable". Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.
Time Frame	At Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Analysis for this outcome was performed on per protocol (PP) population which is defined as all participants in the intent to treat (ITT) population who had at least one assessment of efficacy considered unaffected by protocol violations.

Arm/Group Title	Test Dentifrice	Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
Measure Participants	147	149
At Baseline	53.05 (20.873)	55.89 (21.334)
At Week 8	31.62 (24.194)	30.51 (23.960)
Change from baseline at Week 8	-21.50 (22.231)	-25.16 (22.322)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Dentifrice, Comparator Dentifrice
	Comments	Statistical analysis applies to change from baseline at week 8 for test and comparator dentifrice.
	Type of Statistical Test	Non-Inferiority
	Comments	Inferences: upper end of the 2-sided 95% CI for the treatment difference for the estimated effect of Test relative to Comparator, for success, should be <=6mm. (i.e., Test is no more than 6mm inferior to Comparator).
Statistical Test of Hypothesis	p-Value	0.2678
	Comments	From ANCOVA model: change from baseline as the response variable, treatment group, baseline Schiff stratum and study site as fixed effects, with baseline VAS score as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	2.67
	Confidence Interval	(2-Sided) 95%; -2.06 to 7.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named treatment minus second named dentifrice such that a negative difference favors the first named treatment.

2. Secondary Outcome

Title	Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Visual Analogue Score (VAS) at Week 4
Description	Evaporative air sensitivity was assessed by examiner as a response to a 1 second application of air from a triple air dental syringe applied to the exposed dentine surface of hypersensitive tooth from a distance of approximately 1centimeter. Each participants rated the intensity of their response to the stimulus using a 100 mm VAS, were 0 represented "no pain" and 100 represented the" worst pain imaginable". Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.
Time Frame	At Baseline and Week 4

Outcome Measure Data

Analysis Population Description

Analysis for this outcome was performed on PP population which is defined as all participants in the ITT population who had at least one assessment of efficacy considered unaffected by protocol violations.

Arm/Group Title	Test Dentifrice	Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
Measure Participants	147	149
At Week 4	40.71 (22.828)	40.60 (23.090)
Change from baseline at Week 4	-12.12 (18.438)	-15.24 (19.895)

3. Secondary Outcome

Title	Mean Change From Baseline in Evaporative Air Sensitivity as Measured by Schiff Sensitivity Score at Week 4 and Week 8
Description	Evaporative air sensitivity was measured by examiner as the participant's response to an evaporative air stimulus for each tooth using the Schiff Sensitivity Scale scored as follows - 0: Participant does not respond to air stimulation; 1: responds to air stimulus but does not request discontinuation of stimulus; 2: Participant responds to air stimulus and requests discontinuation or moves from stimulus; 3: Participant responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicate improvement in sensitivity. Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.
Time Frame	At Baseline, Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Analysis for this outcome was performed on PP population which is defined as all participants in the ITT population who had at least one assessment of efficacy considered unaffected by protocol violations.

Arm/Group Title	Test Dentifrice	Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
Measure Participants	147	149
At Baseline	2.72 (0.393)	2.68 (0.400)
At Week 4	2.13 (0.771)	2.11 (0.832)
Change from baseline at Week 4	-0.59 (0.689)	-0.57 (0.745)
At Week 8	1.65 (0.990)	1.58 (1.002)
Change from baseline at Week 8	-1.08 (0.922)	-1.09 (0.937)

4. Secondary Outcome

Title	Change From Baseline in Tactile Threshold at Week 4 and Week 8
Description	Tactile threshold was assessed by examiner using a constant pressure probe (Yeaple probe) which allowed application of a known force to the dentine surface from 10 g to an upper threshold of 80g in increments of 10 g. The tactile threshold is the maximum pressure applied at which participant do not report any pain or discomfort. The tactile threshold for each tooth was determined by asking the participant whether the sensation caused discomfort. The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold. The higher the tactile threshold, the less sensitive the tooth. Change from baseline was calculated as mean score at the given time point minus mean score at baseline of the two selected test teeth.
Time Frame	At Baseline, Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Analysis for this outcome was performed on PP population which is defined as all participants in the ITT population who had at least one assessment of efficacy considered unaffected by protocol violations.

Arm/Group Title	Test Dentifrice	Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.	Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
Measure Participants	147	149
At Baseline	12.79 (3.419)	12.18 (2.982)
At Week 4	25.45 (20.573)	23.61 (18.616)
Change from baseline at Week 4	12.72 (20.181)	11.42 (18.099)
At Week 8	32.88 (25.392)	33.58 (24.840)
Change from baseline at Week 8	20.10 (25.041)	21.42 (24.450)

Adverse Events

Arm/Group Title	Test Dentifrice		Comparator Dentifrice
Arm/Group Description	Test dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium fluoride.		Comparator dentifrice containing 5% w/w calcium sodium phosphosilicate and 1426 ppm fluoride as sodium monofluorophosphate.
All Cause Mortality
	Test Dentifrice		Comparator Dentifrice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/150 (0%)		0/154 (0%)
Serious Adverse Events
	Test Dentifrice		Comparator Dentifrice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/150 (0%)		0/154 (0%)
Other (Not Including Serious) Adverse Events
	Test Dentifrice		Comparator Dentifrice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/150 (34%)		59/154 (38.3%)
Ear and labyrinth disorders
Ear Pain	0/150 (0%)		1/154 (0.6%)
Gastrointestinal disorders
Toothache	4/150 (2.7%)		5/154 (3.2%)
Chapped Lips	1/150 (0.7%)		3/154 (1.9%)
Aphthous Stomatitis	2/150 (1.3%)		1/154 (0.6%)
Mouth ulceration	0/150 (0%)		3/154 (1.9%)
Cheilitis	1/150 (0.7%)		1/154 (0.6%)
Gingival Pain	1/150 (0.7%)		1/154 (0.6%)
Lip Ulceration	0/150 (0%)		2/154 (1.3%)
Nausea	0/150 (0%)		2/154 (1.3%)
Oral discomfort	0/150 (0%)		2/154 (1.3%)
Sensitivity of teeth	0/150 (0%)		2/154 (1.3%)
Stomatitis	1/150 (0.7%)		0/154 (0%)
Oral Mucosal Exfoliation	1/150 (0.7%)		0/154 (0%)
Gastritis	0/150 (0%)		1/154 (0.6%)
Oral Disorder	0/150 (0%)		1/154 (0.6%)
Oral Mucosal Erythema	1/150 (0.7%)		0/154 (0%)
Paraesthesia oral	0/150 (0%)		1/154 (0.6%)
Tongue Discolouration	0/150 (0%)		1/154 (0.6%)
Tongue Ulceration	1/150 (0.7%)		0/154 (0%)
Vomiting	0/150 (0%)		1/154 (0.6%)
General disorders
Device Failure	2/150 (1.3%)		5/154 (3.2%)
Application Site Discomfort	0/150 (0%)		1/154 (0.6%)
Infections and infestations
Rhinitis	9/150 (6%)		12/154 (7.8%)
Oral Herpes	7/150 (4.7%)		2/154 (1.3%)
Upper Respiratory Tract Infection	3/150 (2%)		6/154 (3.9%)
Influenza	2/150 (1.3%)		1/154 (0.6%)
Tonsillitis	1/150 (0.7%)		1/154 (0.6%)
Urinary Tract Infection	0/150 (0%)		2/154 (1.3%)
Ear Infection	0/150 (0%)		1/154 (0.6%)
Eye Infection	0/150 (0%)		1/154 (0.6%)
Hand-Foot-And-Mouth Disease	0/150 (0%)		1/154 (0.6%)
Laryngitis	1/150 (0.7%)		0/154 (0%)
Nail Infection	1/150 (0.7%)		0/154 (0%)
Pharyngitis	0/150 (0%)		1/154 (0.6%)
Tooth Infection	1/150 (0.7%)		0/154 (0%)
Injury, poisoning and procedural complications
Lip Injury	2/150 (1.3%)		2/154 (1.3%)
Tooth fracture	3/150 (2%)		1/154 (0.6%)
Mouth injury	2/150 (1.3%)		1/154 (0.6%)
Traumatic Ulcer	1/150 (0.7%)		2/154 (1.3%)
Procedural Pain	1/150 (0.7%)		1/154 (0.6%)
Fall	1/150 (0.7%)		0/154 (0%)
Head Injury	1/150 (0.7%)		0/154 (0%)
Laceration	1/150 (0.7%)		0/154 (0%)
Ligament Sprain	0/150 (0%)		1/154 (0.6%)
Thermal Burn	1/150 (0.7%)		0/154 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	2/150 (1.3%)		2/154 (1.3%)
Arthralgia	1/150 (0.7%)		0/154 (0%)
Neck Pain	1/150 (0.7%)		0/154 (0%)
Nervous system disorders
Headache	16/150 (10.7%)		8/154 (5.2%)
Migraine	0/150 (0%)		1/154 (0.6%)
Psychiatric disorders
Depression	1/150 (0.7%)		0/154 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	0/150 (0%)		1/154 (0.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/150 (0.7%)		1/154 (0.6%)
Oropharyngeal Pain	1/150 (0.7%)		1/154 (0.6%)
Skin and subcutaneous tissue disorders
Urticaria	0/150 (0%)		1/154 (0.6%)

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.