Study to Characterize the Efficacy of a Dual Active Dentifrice for the Relief of Dentin Hypersensitivity

Study Overview
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Brief Summary
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This exploratory study will characterize the efficacy profile of an experimental dual active 5 percent (%) potassium nitrate/0.454% stannous fluoride dentifrice, compared to a single active 0.454% stannous fluoride desensitizing dentifrice, over an 8-week treatment period.

Detailed Description
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This will be a single center, 8-week, randomized, controlled, examiner-blind, two treatment arm, parallel design, stratified (by maximum Baseline Schiff sensitivity score of the two selected test teeth), Phase II, exploratory clinical study in healthy participants with DH. It is hypothesized that the combination of two antisensitivity active ingredients with complementary modes of action (potassium nitrate: nerve desensitization; stannous fluoride: dentin tubule occlusion) will deliver superior anti-sensitivity efficacy, compared to either active alone.

Official Title
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Randomized Controlled Examiner-Blind Phase II Exploratory Clinical Study to Characterize the Efficacy Profile of an Experimental Dual Active Combination Dentifrice for the Relief of Dentin Hypersensitivity, in Subjects With Clinically Diagnosed Dentin Hypersensitivity

Conditions
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Dentin Hypersensitivity, Dentin Sensitivity

Intervention / Treatment
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* Other: Potassium Nitrate
* Other: Stannous Fluoride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant provision of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed Participant who is willing and able to comply with scheduled visits, treatment plan, and other study procedures Participant in good general, oral and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant/relevant abnormalities in medical history, or upon oral examination, or condition that would impact the Participant's safety, wellbeing or the outcome of the study, if they were to participate in the study, or affect the individual's ability to understand and follow study procedures and requirements Male participant able to father children or female participant of child-bearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 5 days after the last dose of assigned treatment AT VISIT 1 (Screening): Participant must have a self-reported history of dentin hypersensitivity (DH) lasting more than six months but not more than 10 years a minimum of 20 natural teeth a minimum of 2 accessible, non-adjacent teeth (incisors, canines, pre-molars), preferably in different quadrants, with clinically diagnosed DH; each tooth must meet the following criteria: exposed dentin due to facial/cervical erosion, abrasion or gingival recession (EAR) Modified Gingival Index (MGI) score = 0 adjacent to the test area (exposed dentin) only Clinical mobility less than or equal to (=<) 1 DH, as evidenced by qualifying levels of tactile and evaporative air sensitivity (tactile threshold [=<] 20 gram (g); Schiff sensitivity score greater than or equal to [>=] 2) AT VISIT 2 (Baseline): Participant must have a minimum of two, non-adjacent accessible teeth (incisors, canines, pre-molars), preferably in different quadrants, with DH, as evidenced by qualifying tactile and evaporative air sensitivity (each tooth must have a tactile threshold (=<) 20 g and a Schiff sensitivity score (>=) 2) at the Screening and Baseline visits Exclusion Criteria: Participant who is an employee of the investigational site, either directly involved in the conduct of the study or a member of their immediate family; or an employee of the investigational site otherwise supervised by the investigator; or a GlaxoSmithKline Consumer Healthcare (GSK CH) employee directly involved in the conduct of the study or a member of their immediate family Participant who has participated in other studies (including non-medicinal studies) involving investigational product(s) within 30 days prior to study entry and/or during study participation Participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical, oral, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or medically qualified designee, would make the participant inappropriate for entry into this study Participant with any condition which, in the opinion of the investigator or medically qualified designee, causes xerostomia Participant who is a pregnant female (as evidenced by a positive Urine Pregnancy Test [UPT] at Screening) Participant who is a breast-feeding female Participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients Participant with a recent history (within the last year) of alcohol or other substance abuse Participant who has participated in another tooth desensitizing treatment study within 8 weeks Screening Participant who has used an oral care product indicated for the relief of DH within 8 weeks of Screening (participant will be required to bring their current oral care products to the site in order to verify the absence of known anti-sensitivity ingredients) Participant who has had dental prophylaxis within 4 weeks of Screening Participant who has had a tooth bleaching procedure within 8 weeks of Screening Participant who has had treatment for periodontal disease (including surgery) within 12 months of Screening Participant who has had scaling or root planning within 3 months of Screening Participant with gross periodontal disease Participant with evidence of gross intra-oral neglect or the need for extensive dental therapy Participant with a tongue or lip piercing or presence of multiple dental implants Participant with fixed or removable partial dentures Participant with fixed or removable orthodontic braces/bands or a fixed orthodontic retainer SPECIFIC DENTITION EXCLUSIONS FOR 'TEST TEETH': Tooth with evidence of current or recent caries or reported treatment of decay within 12 months of Screening Tooth with exposed dentin but with deep, defective or facial restorations Tooth with full crown or veneer Sensitive tooth with contributing etiologies other than erosion, abrasion or recession to exposed dentin Sensitive tooth not expected to respond to treatment with an over-the-counter dentifrice in the opinion of the investigator Participant taking daily doses of medication/treatments which, in the opinion of the investigator or medically qualified designee, could interfere with the perception of pain (examples of such medications include analgesics, anticonvulsants, antihistamines that cause marked or moderate sedation, sedatives, tranquilizers, antidepressants, mood-altering and anti-inflammatory drugs) AT VISIT 1 (Screening): Participant who has taken antibiotics in the 2 weeks prior to the Screening visit - AT VISIT 2 (Baseline): Participant who has taken antibiotics in the 2 weeks prior to the Baseline visit, during the acclimatization period Participant taking daily doses of a medication which, in the opinion of the investigator or medically qualified designee, is causing xerostomia Participant who requires antibiotic prophylaxis for dental procedures Participant who has previously been enrolled in this study Participant who, in the opinion of the investigator or medically qualified designee, should not participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single center, 8-week, randomized, controlled, parallel design, exploratory clinical study in healthy participants with dentin hypersensitivity. Eligible participants will be stratified by the maximum Baseline Schiff sensitivity score of their two selected test teeth).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Dentifrice<br>Participants will be instructed to apply a strip of dentifrice (a full brush head) containing 5 % weight by weight (w/w) potassium nitrate and 0.454% w/w stannous fluoride (1100 parts per million [ppm] fluoride). Participants will brush their two selected 'test teeth' first, followed by the whole mouth for at least one timed minute, twice daily (morning and evening), and will be permitted to rinse with water post-brushing. | Other: Potassium Nitrate<br>* The test dentifrice contains 5% w/w potassium nitrate.<br>Other: Stannous Fluoride<br>* The test and control dentifrices contain 0.454% w/w stannous fluoride (1100 ppm fluoride).<br>|
| Active Comparator: Control Dentifrice<br>Participants will be instructed to apply a strip of dentifrice (a full brush head) containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Participants will brush their two selected 'test teeth' first, followed by the whole mouth for at least one timed minute, twice daily (morning and evening), and will be permitted to rinse with water post-brushing. | Other: Stannous Fluoride<br>* The test and control dentifrices contain 0.454% w/w stannous fluoride (1100 ppm fluoride).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Baseline (Day 0) | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from standard dental syringe held perpendicular to tooth surface, approximately 1-2 millimeter (mm) coronal to the gingival margin from a distance of approximately 1 centimeter (cm).Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus.0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus,considers stimulus to be painful, requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Baseline (Day 0) | 
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Day 3 | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from a standard dental syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of approximately 1 cm. Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus. 0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement. Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 3 | 
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Day 7 | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from a standard dental syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of approximately 1 cm. Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus. 0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement. Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 7 | 
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Day 14 | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from a standard dental syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of approximately 1 cm. Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus. 0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement. Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 14 | 
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Day 28 | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from a standard dental syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of approximately 1 cm. Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus. 0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement. Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 28 | 
| Mean Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Day 56 | Evaporative air sensitivity was assessed on facial surfaces of eligible incisor,canine and pre-molar teeth by directing a one second application of air from a standard dental syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of approximately 1 cm. Participant response to the stimulus was evaluated using the Schiff sensitivity scale, an examiner-based index scored immediately following administration of the evaporative air stimulus. 0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Score range 0-3; a decrease in Schiff sensitivity score indicates an improvement. Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 56 | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Baseline (Day 0) | Tactile sensitivity was assessed for eligible incisor,canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 gram (g) and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached.The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application,the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response).The pressure setting at which participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g).At Baseline, the maximum force was 20 g;at all subsequent visits, 80 g.If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits).An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Baseline (Day 0) | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Day 3 | Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached. The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline,the maximum force is 20 g; at all subsequent visits, 80 g. If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits). An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 3 | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Day 7 | Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached. The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline,the maximum force is 20 g; at all subsequent visits, 80 g. If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits). An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 7 | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Day 14 | Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached. The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline,the maximum force is 20 g; at all subsequent visits, 80 g. If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits). An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 14 | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Day 28 | Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached. The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline,the maximum force is 20 g; at all subsequent visits, 80 g. If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits). An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 28 | 
| Mean Tactile Threshold (Average of the Two Selected Test Teeth) at Day 56 | Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until the tactile threshold or maximum force for that visit is reached. The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine.After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting at which the participant gave two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline,the maximum force is 20 g; at all subsequent visits, 80 g. If no sensitivity was found at the upper limit,the tactile threshold is recorded as greater than (>) 20 g (baseline) or >80 g (all other visits). An increase in tactile threshold indicates an improvement.Mean was calculated once by selecting two test teeth which were located in different quadrants of mouth. | Day 56 | 
| Number of Sensitive Teeth (Schiff Sensitivity Score Greater Than or Equal to [>=] 1) on Day 0 (Baseline) | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Baseline (Day 0) | 
| Number of Sensitive Teeth (Schiff Sensitivity Score >= 1) on Day 3 | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Day 3 | 
| Number of Sensitive Teeth (Schiff Sensitivity Score >= 1) on Day 7 | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Day 7 | 
| Number of Sensitive Teeth (Schiff Sensitivity Score >= 1) on Day 14 | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Day 14 | 
| Number of Sensitive Teeth (Schiff Sensitivity Score >= 1) on Day 28 | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Day 28 | 
| Number of Sensitive Teeth (Schiff Sensitivity Score >= 1) on Day 56 | Number of eligible teeth were identified at screening with Schiff sensitivity score of >=1 (Schiff sensitivity scale: 0=Participant does not respond to air stimulation; 1=Participant 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 decrease in the number of sensitive teeth indicates an improvement. | Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Schiff Sensitivity Score at Day 56 | Evaporative air sensitivity was assessed on the facial surfaces of teeth by directing one second application of air from dental syringe held perpendicular to tooth surface, approximately 1-2 mm coronal to gingival margin and from a distance of approximately 1 cm. Participant response to stimulus was evaluated using Schiff sensitivity scale following administration of the evaporative air stimulus.0=Does not respond to air stimulation;1=Responds to air stimulus but does not request discontinuation of stimulus;2=Responds to air stimulus and requests discontinuation or moves from stimulus;3=Responds to stimulus, considers stimulus to be painful, requests discontinuation of stimulus. Score range 0-3;a decrease in Schiff sensitivity score indicates improvement. Adjusted mean change from baseline are derived from analysis of covariance (ANCOVA) model which included treatment as a factor and baseline Schiff sensitivity score as a covariate with change from baseline as dependent variable. | Baseline (Day 0), Day 56 | 
| Change From Baseline (Day 0) in Tactile Threshold on Day 56 | Tactile sensitivity was assessed for eligible teeth using constant pressure probe (Yeaple probe),starting at 10 g and rising in increments of 10 g until tactile threshold for that visit is reached. The probe tip was placed perpendicular to facial surface of tooth and drawn slowly across exposed dentine. After each application, participant was asked whether they experienced any pain or discomfort (yes/no response).The pressure setting at which participant gives two consecutive 'yes' responses was recorded as the tactile threshold (g).At Baseline, the maximum force was 20g;at all subsequent visits,80g.If no sensitivity was found at the upper limit, the tactile threshold was recorded as >20 g (Baseline) or >80 g (all other visits).An increase in tactile threshold indicates an improvement. Adjusted mean change from baseline are derived from ANCOVA model which included treatment as factor and baseline tactile senstivity as covariate with change from baseline as dependent variable. | Baseline (Day 0), Day 56 |