A Study Investigating Gingival Crevicular Fluid Biomarkers Following Use of a Commercially Available Toothpaste Containing Stannous Fluoride

This will be a single-center, randomized, controlled, double-blind, split-mouth, 2 treatment arms, parallel group, stratified clinical study in healthy participants with gingivitis and plaque accumulation induced using an experimental gingivitis model, to characterize GCF biomarkers associated with gingival health over time following use of a Test Toothpaste containing stannous fluoride (SnF2) compared to a Regular Fluoride Toothpaste (Reference Toothpaste) on GCF biomarkers. Sufficient participants will be screened to randomize approximately 20 participants (10 per group) to ensure approximately 18 (9 per group) evaluable participants complete the entire study.

• Test Toothpaste (Other): A marketed toothpaste containing 0.454 percent (%) SnF2.
• Regular Fluoride Toothpaste (Other): A marketed toothpaste containing 0.3152% Weight on Weight (w/w) Sodium Fluoride (NaF).

Primary outcomes

• GCF Biomarkers Profile Assessment at Baseline (Day 0), Day 3, 7, 10 and 14 [Baseline (Day 0) and Day 3, 7, 10 and 14]: GCF samples will be collected from the mesio-buccal site of the selected teeth. Proteins will be eluted from the pooled collection papers and then analysed by proximity extension assay.

Secondary outcomes

• GCF Volume at Baseline (Day 0), Day 3, 7, 10 and 14 [Baseline (Day 0) and Day 3, 7, 10 and 14]: GCF samples will be collected from the mesio-buccal site of the selected teeth. The volume of GCF collected on each strip will be quantified using a Periotron device, which measures the fluid absorbed by the PerioPaper strips and provides an estimate of GCF volume.
• Change from Baseline in Modified Gingival Index (MGI) at Day 3, 7, 10 and 14 [Baseline (Day 0) and Day 3, 7, 10 and 14]: The MGI assessment is a non-invasive visual evaluation to assess the symptoms of gingivitis. It will be assessed for all evaluable teeth, four sites per test and reference tooth. For each tooth, 3 scores will be recorded and will be scored on a 5-point scale ranging from 0 to 4, where 0 equals (=) Absence of inflammation, 1= Mild inflammation: slight change in color, little change in texture of any portion of the marginal or papillary gingival unit, 2= Mild inflammation: criteria as (1) but involving the entire marginal or papillary gingival unit, 3= Moderate inflammation: glazing, redness, edema, and/or hypertrophy of the marginal or papillary gingival unit, 4= Severe inflammation: marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration. Change from baseline will be calculated by subtracting the Baseline score from the score at the indicated timepoints. Lower score will indicate an improvement in condition.
• Change from Baseline in Turesky modification of the Quigley Hein Plaque Index (TPI) at Day 3, 7, 10 and 14 [Baseline (Day 0) and Day 3, 7, 10 and 14]: TPI will be used to assess plaque on all gradable test and reference teeth. The plaque will first be disclosed using a plaque disclosing dye solution. The disclosed plaques will be scored using a 6-point scale ranging from 0 to 5, where 0= No plaque, 1= Separate flecks of plaque at the cervical margin, 2= Thin continuous band of plaque \[up to 1 millimeter (mm)\] at the cervical margin, 3= Band of plaque wider than 1 mm but covering less than (<) 1/3 of the tooth surface, 4= Plaque covering more than equal to (>=) 1/3 but < 2/3 of the tooth surface, 5= Plaque covering >= 2/3 of the tooth surface. Change from baseline will be calculated by subtracting the Baseline score from the score at the indicated timepoints. Lower score will indicate improvement in gingival health.

Sex: All, ages: 18 Years to 70 Years, accepts healthy volunteers

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.
* A participant is willing and able to comply with scheduled visits, and other study procedures and restrictions including the lifestyle restrictions.
* A participant is 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 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.
* A participant with probing pocket depths of less than (<) 3.5mm and a minimum of four teeth from maxillary canine to third molar in both maxillary quadrants that are scorable (including two molars and at least one premolar) at screening.
* A participant has, localized, plaque induced gingivitis at screening, defined as >= 10 and less than equal to (<=) 30% of sites exhibiting bleeding on probing (BOP).
* A participants have a canine, one or two premolars, and two or three molars present in each maxillary quadrant (right and left side).

Exclusion Criteria:

* A 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 Haleon employee directly involved in the conduct of the study or a member of their immediate family.
* A 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.
* A 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 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.
* A participant who is breast feeding, is pregnant (self-reported) or intending to become pregnant over the duration of the study.
* A participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
* A participant unwilling or unable to comply with the lifestyle considerations described in this protocol.
* A participant with a recent history (within the last year) of alcohol or other substance abuse.
* Participant who:

  1. Is taking antibiotics during the study or has taken antibiotics in the two weeks prior to the screening visit.
  2. Is using or has used an anti-bacterial toothpaste/mouthwash (e.g., chlorhexidine) or another oral care product within 2 weeks of Screening that, in the opinion of the investigator or dentally qualified designee, could affect plaque formation or gingival health.
  3. Currently taking a systemic medication (e.g., anti-inflammatory, anticoagulant, immunosuppressants) or traditional/ herbal remedy which, in the opinion of the Investigator, could affect plaque/ gingival condition (e.g., ibuprofen, aspirin, warfarin, cyclosporin, phenytoin, calcium channel blockers).
  4. Smokes or uses smokeless forms of tobacco (example \[e.g.\] chewing tobacco, gutkha, pan containing tobacco, e-cigarettes \[vapes\]).
  5. Is diagnosed with xerostomia or who the investigator believes might suffer from xerostomia based upon medications or oral examination.
  6. Has a tongue or lip piercing, or any other oral feature that, in the opinion of the investigator, could interfere with the proper usage of a toothbrush.
  7. Has, in the opinion of the investigator or medically qualified designee, signs of active periodontal disease or who is receiving or has received treatment for periodontal disease (including surgery) within 12 months of Screening.
  8. Requires immediate dental intervention to resolve any oral condition.
  9. Has dentures (partial or full) or has an orthodontic appliance (bands, appliances, or fixed/ removable retainers) that, in the opinion of the investigator, could interfere with the proper usage of a toothbrush.
  10. A participant who has had teeth bleaching within 12 weeks of Screening.
* A participant who has previously been enrolled in this study.
* A participant who, in the opinion of the investigator or medically qualified designee, should not participate in the study.

• Praveen Sharma, Principal investigator, University of Birmingham