Study to Investigate the Stain Control of Two Stannous Fluoride Dentifrices

This proof of principal (PoP) single centre, randomised, examiner blind, four-treatment arm, parallel design study will be used to evaluate and compare the stain buildup of two 0.454% SnF2/ 5% STP dentifrices of differing abrasivity levels, with a marketed standard fluoride dentifrice and a marketed SnF2 dentifrice. Stain will be assessed following a full professional dental prophylaxis, at intervals over a 4 week treatment period, using an established clinical measure of extrinsic dental stain - the MacPherson modification of the Lobene stain index (MLSI). Participants will be stratified by pre-prophylaxis MLSI score (total MLSI Area x Intensity (A×I) for the facial surfaces of the 12 anterior teeth) and smoking status. The study will be conducted in healthy participants with a propensity for extrinsic dental stain (in the opinion of the examiner) on the facial surfaces of the anterior teeth.

• Stannous fluoride (SnF2, 0.454%), Sodium tripolyphosphate (STP, 5%), 2.0% abrasive silica (Other): Participants will apply a full brush head of their dentifrice containing 0.454% SnF2 / 5% STP; 2.0% abrasive silica (RDA\~58) and will brush twice daily (morning and evening) for one timed minute (in their usual manner) and expectorate.
• Stannous fluoride (SnF2, 0.454%), Sodium tripolyphosphate (STP, 5%), abrasive silica (3.5%) (Other): Participants will apply a full brush head of their dentifrice containing 0.454% SnF2 / 5% STP; 3.5% abrasive silica (RDA\~77) and will brush twice daily (morning and evening) for one timed minute (in their usual manner) and expectorate.
• Sodium Monofluorophosphate (1000 ppm fluoride ), RDA~80 (Other): Participants will apply a full brush head of their dentifrice containing 1000 ppm fluoride as SMFP with moderate abrasivity (RDA\~80) and will brush twice daily (morning and evening) for one timed minute (in their usual manner) and expectorate.
• Stannous fluoride (SnF2, 0.454%), RDA~120 (Other): Participants will apply a full brush head of their dentifrice containing 0.454% SnF2 with higher abrasivity (RDA\~120) and will brush twice daily (morning and evening) for one timed minute (in their usual manner) and expectorate.

Primary outcomes

• Overall Modified Lobene Stain Index (MLSI) Mean Score at Week 4 [Baseline and Week 4]: An assessment of the area and intensity of dental stain on the study teeth was performed using the MLSI after usage of the allocated study dentifrice, after 4 weeks twice daily use. 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).

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.
* Understands and is willing, able and likely to comply with all study procedures and restrictions.
* 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, Absence of any condition that would impact on subject safety or wellbeing, or affect the subject's ability to understand and follow study procedures and requirements.
* In the opinion of the investigator or medically qualified designee, At screening: Good oral health, at least 16 natural teeth including the 12 anterior teeth, the facial surfaces, and mandibular lingual surfaces, of at least 11 of the 12 anterior teeth, gradable for the MLSI, presence of extrinsic dental stain (judged to be formed due to dietary factors, or use of tobacco products) on the facial surfaces of the anterior teeth, as determined from a visual stain assessment. At baseline: 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.

Exclusion Criteria:

* Women who are known to be pregnant, or who are intending to become pregnant over the duration of the study. Since this study is not being conducted under an IND this information will be self-reported, and not diagnosed through the conduct of urinary pregnancy testing.
* Women who are breast-feeding.
* Recent history (within the last year) of alcohol or other substance abuse.
* Concurrent Medication: Current regular use of mouthwashes containing ingredients that are known to impart staining. For example, chlorhexidine or cetylpyridinium chloride (CPC), Use of minocycline, tetracycline or doxycycline within 30 days prior to screening, Use of minocycline, tetracycline or doxycycline between the screening and baseline visit, 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.
* Disease: Presence of chronic debilitating disease which, in the opinion of the investigator, could affect study outcomes, Any condition which, in the opinion of the investigator, causes xerostomia.
* Allergy/Intolerance:Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
* Clinical study/Experimental Product:Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit, Previous participation in this study.
* General dentition exclusions: Dental prophylaxis within 8 weeks of screening, Gross periodontal disease, treatment of periodontal disease (including surgery) within 12 months of screening, scaling or root planning within 3 months of screening, Use of any professionally dispensed or over the counter bleaching/ whitening products (excluding daily use whitening dentifrices) within the past 3 months.
* Specific Dentition Exclusions for Test Teeth: Any tooth which, in the opinion of the investigator, appears to be non-vital based on changes in the intrinsic colour, tooth with evidence of current or recent caries, or reported treatment of decay in 12 months of screening, 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, 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.
* Personnel: An employee of the sponsor or the study site or members of their immediate family.
* Other: Any subject who, in the judgment of the investigator, should not participate in the study.

Participant flow

Outcome results

• Overall Modified Lobene Stain Index (MLSI) Mean Score at Week 4 (Primary), Mean, Score on a scale: Test Dentifrice 1 (RDA~58) 1.38 +/- 0.423; Test Dentifrice 2 (RDA~77) 1.43 +/- 0.422; Reference Dentifrice 1 (RDA~80) 1.42 +/- 0.626; Reference Dentifrice 2 (RDA~120) 1.38 +/- 0.443 (p 0.2681)

Adverse events

Time frame: Approximately 35 days (28+/- 2 days, maximum 30 days plus 5 days follow up after last use of study product.

Other adverse events by term

• Results publication: Mason S, Young S, Qaqish J, Frappin G, Goyal C. Stain control with two modified stannous fluoride/sodium tripolyphosphate toothpastes: A randomised controlled proof of concept study. J Dent. 2019;91S:100009. doi: 10.1016/j.jjodo.2019.100009. Epub 2019 Oct 7. PMID 34059275

• Study Protocol (PDF, 2017-05-30)
• Statistical Analysis Plan (PDF, 2017-09-15)

• GSK Clinical Trials, Study director, GlaxoSmithKline