Clinical Study to Investigate the Tooth Stain Removal Efficacy of Two Experimental Toothpastes Compared to a Standard Toothpaste When Used Twice Daily for 8 Weeks

Study Overview
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Brief Summary
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The aim of this study is to investigate the stain removal efficacy of 2 experimental anti-dentin hypersensitivity (DH) dentifrices with four and eight weeks twice daily use. A daily use, regular fluoride dentifrice will be included as a reference dentifrice.

Detailed Description
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This will be a single-center, 8-week, randomized, controlled, single-blind, three treatment-arm, parallel design, stratified clinical study in healthy volunteers with a propensity to form dental stain. It has been designed to investigate changes in tooth stain and color, following twice-daily use of two experimental dentifrices, after four and eight weeks twice daily use; a regular fluoride dentifrice will be included as reference dentifrice. Sufficient participants will be screened to randomize approximately 300 participants to study treatment to ensure approximately 270 participants complete the study.

Official Title
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A Randomized, Controlled, Single-Blind Clinical Study to Investigate the Tooth Stain Removal Efficacy of Two Experimental Potassium Nitrate Dentifrices in Subjects With Extrinsic Dental Stain Compared to a Standard Dentifrice Control When Used Twice Daily for 8 Weeks

Conditions
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Oral Hygiene

Intervention / Treatment
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* Drug: Experimental Dentifrice 1
* Drug: Experimental Dentifrice 2
* Drug: Reference Dentifrice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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, product usage requirements, study procedures and lifestyle restrictions. Participant in good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant or relevant abnormalities in medical history (for example, a medical condition confirmed to be causing xerostomia),or upon oral examination, that would impact the participant's safety, wellbeing or the outcomes of the study, if they were to participate in the study, or affect the participant's ability to understand and follow study procedures and requirements. Participant with generally good oral health with: At least 16 natural (vital) teeth including 11 of the 12 anterior teeth. Facial surfaces of all anterior teeth (maxillary and mandibular) and lingual surfaces of anterior teeth (mandibular only) gradable for MLSI with no significant calculus or large restorations as judged by the clinical examiner. Presence of extrinsic dental stain (formed on the surface of the teeth) as determined from a gross visual examination which, in the opinion of the clinical examiner, originates from the diet and/or use of tobacco products. Facial surfaces of central and lateral maxillary incisors gradable for tooth shade (free of cervical margin defects and restorations which could impact assessment), as judged by the clinical examiner. Baseline Total MLSI (Area x Intensity) greater than or equal to (>=)15 for the facial surfaces of the 12 anterior teeth. Baseline mean tooth shade (VITA Bleachedguide 3D-MASTER) >=11 on the facial surfaces of the 4 maxillary incisors. 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 an employee of the sponsor 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 of study entry and/or during study participation or who has previously been enrolled in this study. Participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study 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 who is pregnant (self-reported) or intending to become pregnant during the study. Participant who is breastfeeding. Participant with known or suspected intolerance or hypersensitivity to the study products or any of their stated ingredients (or closely related compounds). Participant who is unwilling or, in the opinion of the investigator or medically qualified designee, unable to comply with the requirements and/or lifestyle restrictions of the study. Participant with a recent history (within the last year) of alcohol or other substance abuse. Participant with Oral Soft Tissue (OST) examination findings at Screening which, in the opinion of the investigator, could interfere with the conduct of the study (for example, stomatitis, open sores, lesions, cavitied caries lesions, redness or swelling. Participant using daily oral care products and/or taking daily doses of medications/treatments which, in the opinion of the investigator or medically qualified designee, could interfere with study outcomes, specifically: currently daily use of mouthwashes containing ingredients known to cause tooth stain (for example, chlorhexidine or cetylpyridinium chloride), past or current use of minocycline, use of tetracycline or doxycycline within 30 days of screening and/or during the study, medications known to cause tooth stain (for example, drugs or supplements containing metal ions known to increase enamel staining). Participant who has used any professionally-dispensed tooth whitening products 6 months prior to baseline or any over-the-counter products (including peroxide- or covarine blue-containing dentifrice, but not other daily use whitening dentifrices) 3 months prior to baseline. Specific exclusions for assessment teeth: Non-vital tooth. Tooth with evidence of current or recent carious lesions. Tooth used as an abutment for fixed or partial dentures. Tooth adjacent to fixed retainers and fixed or removable orthodontic appliances. Tooth with surface irregularities, cracked enamel, discoloration due to trauma or orthodontic treatment, tetracycline stain, restorations or hyper-/hypoplastic areas, which, in the opinion of the clinical examiner, grading of extrinsic dental stain and tooth shade. Tooth with a crown or veneer. Tooth with exposed dentine which, in the opinion of the investigator, could impact grading of extrinsic dental stain and tooth shade. General oral exclusions: Generalized severe gingivitis or advanced periodontal disease; treatment of periodontal disease (including surgery) within 12 months of screening; scaling or root planning within 3 months of screening. Any oral condition requiring immediate care. Having received a dental prophylaxis within 8 weeks of screening. Participant who, in the opinion 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: Experimental Dentifrice 1<br>Randomized participants will brush their teeth with the experimental dentifrice (covering the entire length of the toothbrush), twice daily (morning and evening) for 2 minutes for 8 weeks. | Drug: Experimental Dentifrice 1<br>* 5 percent (%) potassium nitrate (KNO3) dentifrice with 1% alumina and 5% sodium tripolyphosphate (STP).<br>|
| Experimental: Experimental Dentifrice 2<br>Randomized participants will brush their teeth with the experimental dentifrice (covering the entire length of the toothbrush), twice daily (morning and evening) for 2 minutes for 8 weeks. | Drug: Experimental Dentifrice 2<br>* 5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica.<br>|
| Active Comparator: Reference Dentifrice<br>Randomized participants will brush their teeth with the Reference dentifrice (covering the entire length of the toothbrush), twice daily (morning and evening) for 2 minutes for 8 weeks. | Drug: Reference Dentifrice<br>* Regular Fluoride Dentifrice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Mean Total Macpherson Modification of the Lobene Stain Index (MLSI) Score at Week 8 | Extrinsic dental stain and its intensity will be assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. Total MLSI score= Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain will be scored separately for each tooth on the scale 0 to 3 and the mean total score will be presented, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Total score ranges from 0 to 9, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the Week 8 value. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Mean Total MLSI Score at Week 4 | Extrinsic dental stain and its intensity will be assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. Total MLSI score = Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain will be scored separately for each tooth on the scale 0 to 3 and the mean total score will be presented, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Total score ranges from 0 to 9, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the Week 4 value. | Baseline and Week 4 | 
| Change from Baseline in Mean Total MLSI Score at Weeks 4 and 8 | Extrinsic dental stain and its intensity will be assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. Total MLSI score = Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain will be scored separately for each tooth on the scale 0 to 3 and the mean total score will be presented, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Total score ranges from 0 to 9, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the value at indicated timepoints. | Baseline, Week 4 and Week 8 | 
| Change from Baseline in Mean VITA Shade Score (Examiner Assessed) at Weeks 4 and 8 | Tooth shade (color) of the facial surfaces of the four central and lateral maxillary incisors will be assessed by a trained clinical examiner using the VITA Bleachedguide 3D-MASTER. It uses a value-ranked ordered scale from 1 (the lightest) to 29 (the darkest). The shade level of each tooth surface is scored visually by the clinical examiner with reference to the Bleachedguide, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the value at indicated timepoints. | Baseline, Week 4 and Week 8 | 
| Change from Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 | Extrinsic dental stain and its intensity will be assessed at the specific tooth sites. The gingival site is defined as a crescent-shaped band, approximately 2 millimeter wide, adjacent to the free margin of the gingiva and extending to the crest of the interdental papillae of the adjacent teeth. The remainder of the tooth surface is called as Body site. Total MLSI score= Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain will be scored separately for each tooth on the scale 0 to 3 and the mean total score will be presented, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Total score ranges from 0 to 9, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the value at indicated timepoints. | Baseline, Week 4 and Week 8 | 
| Change from Baseline in Mean MLSI (Area) and MLSI (Intensity) at Weeks 4 and 8 | Extrinsic dental stain and its intensity will be assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. Area and intensity of extrinsic dental stain will be scored separately for each tooth on the scale 0 to 3 and the separate mean score will be presented for both area and intensity, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Total score ranges from 0 to 3, where lower score indicates improvement. Change from Baseline will be calculated by subtracting the Baseline value from the value at indicated timepoints. | Baseline, Week 4 and Week 8 |