A Study to Investigate the Stain and Plaque Removal Capability of Two Experimental Potassium Nitrate Dentifrices

Study Overview
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Brief Summary
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The purpose of this study is to determine whether spherical silica can achieve similar or greater extrinsic dental stain and plaque removal, in comparison to dentifrices containing higher concentrations of standard abrasive silica, and how the addition of 5% sodium tripolyphosphate (STP) enhances cleaning capability.

Detailed Description
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This proof of principal (PoP) single centre, randomised, examiner blind, four-treatment arm, parallel design study will be conducted in healthy participants with a propensity for extrinsic dental stain (based on the judgement of the examiner) on the facial surfaces of the anterior teeth. This study will be used to evaluate and compare the extrinsic dental stain and plaque removal of an experimental low abrasivity 0.5% spherical silica dentifrice and a marketed low abrasivity 6% standard silica abrasive dentifrice, and an experimental moderate abrasivity 1% spherical silica / 5% STP dentifrice and a marketed high abrasivity 16% standard abrasive silica / 5% STP dentifrice. Stain will be assessed using an established clinical measure of extrinsic dental stain - the MacPherson modification of the Lobene stain index (MLSI). Particpants will be stratified by baseline MLSI score (total MLSI (area [A] × intensity [I]) for the facial surfaces of the 4 anterior assessment teeth). Plaque will be assessed using an established clinical measure of plaque - the Turesky Modification of the Quigley Hein Index. Stain and plaque will be assessed at intervals over an 8 week treatment period. Plaque will be assessed at baseline and Week 8 only.

Official Title
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A Randomized, Examiner-blind, Proof of Principal Study to Investigate the Stain and Plaque Removal Capability of Two Experimental 5% Potassium Nitrate Dentifrices in Healthy Subjects With the Propensity for Extrinsic Dental Stain

Conditions
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Oral Hygiene

Intervention / Treatment
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* Drug: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica
* Drug: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP
* Drug: 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica
* Drug: 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally 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. Male and female participants who, at the time of screening, are between the ages of 18 and 65 years, inclusive. Participants who are willing and able to comply with scheduled visits, treatment plan, and other study procedures. Good general and mental health with, in the opinion of the investigator or medically qualified designee no clinically significant and relevant abnormalities of medical history or oral examination which could impact study outcomes. Good general and mental health with, in the opinion of the investigator or medically qualified designee an absence of any condition that would impact on participant safety or wellbeing, or affect the participant's ability to understand and follow study procedures and requirements. In the opinion of the investigator or medically qualified designee, at screening, participants must have good oral health. In the opinion of the investigator or medically qualified designee, at screening, participants must have at least 20 natural teeth including the 12 anterior teeth, gradable for Turesky Plaque Index (TPI) (Gradable teeth are those where restorative materials cover less than 25% of the tooth surface to be graded). In the opinion of the investigator or medically qualified designee, at screening, participants must have the facial surfaces of at least 4 of the anterior teeth, gradable for the MLSI. In the opinion of the investigator or medically qualified designee, at screening, participants must have the presence of extrinsic dental stain (judged to be formed due to dietary factors) on the facial surfaces of the anterior teeth, as determined from a visual MLSI stain assessment. In the opinion of the investigator, at Visit 2, participants must have a sufficient level of extrinsic dental stain (in the opinion of the examiner) on the facial surfaces of the scorable anterior (maxillary and mandibular) teeth. At Visit 3, a minimum overall pre-brushing plaque score (TPI) of ≥2.0. Exclusion Criteria: Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are GSK employees directly involved in the conduct of the study. Participation in another clinical study or receipt of an investigational drug(s) within 30 days prior to study entry and/or during study participation. Participants who have previously been enrolled in this study. Acute or chronic medical or 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, would make the participant inappropriate for entry into this study. Any condition which, in the opinion of the investigator, causes xerostomia. Pregnant female participants. Breastfeeding female participants. Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. Unwilling or unable to comply with the lifestyle guidelines described in this protocol. Recent history (within the last year) of alcohol or other substance abuse. Participant is unwilling to abstain from tobacco or nicotine-containing product use (including E-cigarettes) during the treatment evaluation period. Participants using the following mouth rinses, or taking the medications listed below: a) Regular use of mouthwashes containing ingredients that are known to impart staining. For example, chlorhexidine, essential oils or cetylpyridinium chloride (CPC). b) Use of a chlorhexidine, essential oil or CPC containing mouthwash within 14 days of Visit 2 or throughout the study. c) Current use of Listerine, or any antimicrobial mouth rinse. d) Use of minocycline, tetracycline or doxycycline within 30 days prior to screening. e) Use of minocycline, tetracycline or doxycycline between the screening and baseline visits. f) Daily doses of a medication and/or traditional/herbal ingredients which, in the opinion of the investigator, may affect study outcomes. For example, drugs or supplements containing metal ions known to impart staining to the enamel. Participants who have the following dental exclusions: a) Received a dental prophylaxis within 8 weeks of screening. b) Gross periodontal disease, treatment of periodontal disease (including surgery) within 12 months of screening, scaling or root planning within 3 months of screening. c) Dental conditions / disease requiring immediate treatment. d) Used any professionally dispensed or over the counter bleaching/ whitening products (excluding daily use whitening dentifrices) within the past 3 months. Participants who have the following specific dental exclusions for assessment teeth: a) Any tooth which, in the opinion of the investigator, appears to be non-vital based on changes in the intrinsic colour. b) Tooth with evidence of current or recent caries, or reported treatment of decay in 12 months of screening. c) Tooth with exposed dentine which, in the opinion of the investigator, could impact grading of extrinsic dental stain; tooth with deep, defective or facial restorations; tooth used as an abutment for fixed or removable partial dentures; tooth with full crown or veneer, orthodontic bands or cracked enamel. d) Tooth with surface irregularities, discoloration due to trauma, tetracycline stain, restorations, or hypo or hyperplasic areas which, in the opinion of the investigator, would prevent consistent grading of extrinsic dental stain. e) High levels of calculus deposits which might interfere with plaque assessments at the discretion of the investigator. f) Presence of orthodontic bands or appliances, extensive crowns, partial dentures, or fixed retainers. Any participant who, in the judgment of the investigator, 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Product 1<br>Participants will be instructed to apply experimental dentifrice containing 5% potassium nitrate (KNO3) / 0.2542% sodium fluoride (NaF) dentifrice with 0.5% spherical silica. | Drug: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica<br>* Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica and brush twice daily (morning and evening) for one timed minute (in their usual manner).<br>|
| Experimental: Test Product 2<br>Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP. | Drug: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP<br>* Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP and brush twice daily (morning and evening) for one timed minute (in their usual manner).<br>|
| Active Comparator: Reference Product 1<br>Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica. | Drug: 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica<br>* Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica and brush twice daily (morning and evening) for one timed minute (in their usual manner).<br>|
| Active Comparator: Reference Product 2<br>Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP. | Drug: 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP<br>* Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP and brush twice daily (morning and evening) for one timed minute (in their usual manner).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Overall Macpherson Modification of the Lobene Stain Index (MLSI) at 8 Weeks. | An assessment of the area and intensity of dental stain on the study teeth was performed using the MLSI to evaluate ranking order in extrinsic dental stain removal or reduction of test product 1, test product 2, reference product 1, reference product 2; after usage for 8 weeks, twice daily brushing. The intensity of stain was scored separately for the gingival and body areas of each assessable tooth on a scale of 0 to 3 (0 - no stain, 1- light stain, 2 - moderate stain, 3 - heavy stain). The area of stain was scored separately for the gingival and body areas of each assessable tooth on the following scale: 0 - no stain; 1 - stain up to 1/3 of the area affected; 2- stain between 1/3 and 2/3 of the area affected; and 3 - stain more than 2/3 of area affected. Overall MLSI was calculated by multiplying scores of intensity and area, and was thus analyzed on a scale of 0 (best score) to 9 (worst score). | Baseline, Week 8 post treatment administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of Least Square Mean of Change From Baseline in Overall MLSI After 8 Weeks (Test Product 1 Versus vs. Reference Product 1) | An assessment of the area and intensity of dental stain on the study teeth will be performed using the MLSI after usage test product 1 and reference product 1 for 8 weeks, twice daily brushing. The intensity of stain was scored separately for the gingival and body areas of each assessable tooth on a scale of 0 to 3 (0 - no stain, 1- light stain, 2 - moderate stain, 3 - heavy stain). The area of stain was scored separately for the gingival and body areas of each assessable tooth on the following scale: 0 - no stain; 1 - stain up to 1/3 of the area affected; 2- stain between 1/3 and 2/3 of the area affected; and 3 - stain more than 2/3 of area affected. Overall MLSI will be calculated by multiplying scores of intensity and area, and will be thus analyzed on a scale of 0 (best score) to 9 (worst score). | Baseline, Week 8 post treatment administration | 
| Difference of Least Square Mean of Change From Baseline in Overall MLSI After 8 Weeks (Test Product 2 Versus vs. Reference Product 2) | An assessment of the area and intensity of dental stain on the study teeth will be performed using the MLSI after usage test product 2 and reference product 2 for 8 weeks, twice daily brushing. The intensity of stain was scored separately for the gingival and body areas of each assessable tooth on a scale of 0 to 3 (0 - no stain, 1- light stain, 2 - moderate stain, 3 - heavy stain). The area of stain was scored separately for the gingival and body areas of each assessable tooth on the following scale: 0 - no stain; 1 - stain up to 1/3 of the area affected; 2- stain between 1/3 and 2/3 of the area affected; and 3 - stain more than 2/3 of area affected. Overall MLSI will be calculated by multiplying scores of intensity and area, and will be thus analyzed on a scale of 0 (best score) to 9 (worst score). | Baseline, Week 8 post treatment administration |