Gingivitis
Conditions
Brief summary
This will be a single-center, 12 week, examiner-blind, randomized, stratified (gender and baseline mean whole mouth MGI score), two-treatment, parallel group, clinical study in healthy adult volunteers with moderate gingivitis. This study will evaluate the efficacy of a dentifrice containing 0.454% weight by weight (w/w) stannous fluoride to control gingivitis and gingival bleeding following 12 weeks twice daily brushing, compared to a negative control dentifrice.
Interventions
DRUGStannous Fluoride
Dentifrice containing 0.454% w/w stannous fluoride
Dentifrice containing 1000ppm fluoride as sodium monofluorophosphate
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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. * Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or oral/dental examination. * Absence of any condition that would impact on the subject's safety or wellbeing or affect the individual's ability to understand and follow study procedures and requirements. * A minimum of 20 permanent gradable teeth. (Gradable teeth are those where restorative materials cover less than 25% of the tooth surface graded). * Moderate gingivitis present at the screening visit in the opinion of the investigator from a gross visual gingival assessment. * Visible blood in toothpaste expectorant at Screening and Baseline (Visit 2).
Exclusion criteria
* Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. * Women who are breast-feeding * Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. * Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 30 days of the screening visit. * Previous participation in this study. * Recent history (within the last year) of alcohol or other substance abuse. * An employee of the sponsor or the study site or members of their immediate family. * An employee of any toothpaste manufacturer or their immediate family. * Medical History/Current Medication A. Current or relevant history of any serious, severe or unstable physical or psychiatric illness or any other medical condition (e.g. Diabetes Mellitus) that would make the subject unlikely to fully complete the study or any that increases the risk to the subject or undermines the data validity B.Screening i. Currently taking antibiotics or requiring antibiotic use prior to dental prophylaxis or other dental procedures. ii. Currently taking an anti-inflammatory medication which, in the opinion of the Investigator, could affect gingival condition. iii. Currently taking a systemic medication which, in the opinion of the C. Baseline, Day 28 and Day 96 Assessment Visits i. Has taken antibiotics in the previous 14 days. ii. Has taken an anti-inflammatory medication which, in the opinion of the investigator, could affect gingival condition in the previous 14 days. iii. Has taken a systemic medication which, in the opinion of the investigator, could affect gingival condition in the previous 14 days (e.g. calcium channel blockers, or aspirin therapy).could affect gingival condition in the previous 14 days (e.g. calcium channel blockers, or aspirin therapy).Investigator, could affect gingival condition (e.g. calcium channel blockers, or aspirin therapy). * Have current active caries or periodontitis that may, in the opinion of the investigator, compromise the study or the oral health of the subjects if they participate in the study. * Restorations in a poor state of repair. * Partial dentures or orthodontic appliances. * Teeth bleaching within 12 weeks of screening. * Use of a chlorhexidine mouthwash within 14 days of baseline. * Current smokers or smokers who have quit within the past 6 months prior to screening or subjects currently using smokeless forms of tobacco, e.g. Gutkha, Pan containing tobacco, Pan Masala or nicotine based e-cigarettes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Bleeding Sites at Week 12 | Week 12 | Number of bleeding sites was measured as bleeding index (BI) via a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 millimetre (mm) into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI was assessed on the facial and lingual gingival surfaces of each scorable tooth (7-7 in each arch). The BI scoring system used to measure bleeding sites is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed. Bleeding sites were assessed as the number of bleeding sites with a BI score of 1 or 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Bleeding Sites at Week 4 | Week 4 | Number of bleeding sites was measured as BI via a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI was assessed on the facial and lingual gingival surfaces of each scorable tooth (7-7 in each arch). The BI scoring system used to measure bleeding sites is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed. Bleeding sites were assessed as the number of bleeding sites with a BI score of 1 or 2. |
| Bleeding Index (BI) at Week 4 and Week 12 | Week 4, Week 12 | BI was assessed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system to be used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed |
| Modified Gingival Index (MGI) at Week 4 and Week 12 | Week 4, Week 12 | MGI was assessed on facial and lingual surfaces at two sites on each tooth (papillae and margin). The scoring of the MGI was performed under dental office conditions using a standard dental light for illuminating the oral cavity. This procedure was performed by a single examiner. The MGI scoring system is as follows: 0 = absence of inflammation; 1 = mild inflammation; slight change in color, little change in color; little change in texture of any portion of the marginal or papillary gingival unit; 2 = mild inflammation; criteria as above but involving the entire marginal or papillar gingival units; 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. |
| Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | Week 4, Week 12 | Visible blood in expectorate for each participant was classified as (i) Present (Trace or Substantial) (ii) Absent. The number of participants with blood 'Present' (Trace or Substantial) or 'absent' in expectorate was analyzed. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited in a single center in Germany.
Pre-assignment details
A total of 317 participants were screened. Out of which only 253 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Stannous Fluoride Participants were instructed to apply a full ribbon of dentifrice containing 0.454% w/w stannous fluoride to the study toothbrush and brush their teeth in their usual manner for one timed minute twice daily (morning and evening) for 12 weeks. | 125 |
| Sodium Monofluorophosphate Participants were instructed to apply a full ribbon of dentifrice containing 1000 ppm fluoride as sodium monofluorophosphate to the study toothbrush and brush their teeth in their usual manner for one timed minute twice daily (morning and evening) for 12 weeks. | 128 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Stannous Fluoride | Sodium Monofluorophosphate | Total |
|---|---|---|---|
| Age, Continuous | 39.39 Years STANDARD_DEVIATION 13.61 | 36.37 Years STANDARD_DEVIATION 13.179 | 37.86 Years STANDARD_DEVIATION 13.453 |
| Sex: Female, Male Female | 71 Participants | 73 Participants | 144 Participants |
| Sex: Female, Male Male | 54 Participants | 55 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 125 | 22 / 128 |
| serious Total, serious adverse events | 0 / 125 | 0 / 128 |
Outcome results
Primary
Number of Bleeding Sites at Week 12
Number of bleeding sites was measured as bleeding index (BI) via a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 millimetre (mm) into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI was assessed on the facial and lingual gingival surfaces of each scorable tooth (7-7 in each arch). The BI scoring system used to measure bleeding sites is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed. Bleeding sites were assessed as the number of bleeding sites with a BI score of 1 or 2.
Time frame: Week 12
Population: Intent to treat (ITT) population which included all participants who were randomized, received at least one dose of study product and had at least one post-baseline efficacy measurement. Number of participants analyzed is the number of participants from ITT population evaluated for this outcome at Week 12 for respective treatment arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stannous Fluoride | Number of Bleeding Sites at Week 12 | 42.02 number of bleeding sites | Standard Error 1.91 |
| Sodium Monofluorophosphate | Number of Bleeding Sites at Week 12 | 67.36 number of bleeding sites | Standard Error 1.91 |
p-value: <0.000195% CI: [-30.682, -19.998]ANCOVA
Secondary
Bleeding Index (BI) at Week 4 and Week 12
BI was assessed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system to be used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed
Time frame: Week 4, Week 12
Population: Intent to treat (ITT) population which included all participants who were randomized, received at least one dose of study product and had at least one post-baseline efficacy measurement. Number of participants analyzed is the number of participants from ITT population evaluated for this outcome at specific time points for respective treatment arm.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Stannous Fluoride | Bleeding Index (BI) at Week 4 and Week 12 | BI at Week 4 (n=121, 122) | 0.29 score on a scale | Standard Error 0.01 |
| Stannous Fluoride | Bleeding Index (BI) at Week 4 and Week 12 | BI at Week 12 (n=119, 119) | 0.27 score on a scale | Standard Error 0.01 |
| Sodium Monofluorophosphate | Bleeding Index (BI) at Week 4 and Week 12 | BI at Week 4 (n=121, 122) | 0.44 score on a scale | Standard Error 0.01 |
| Sodium Monofluorophosphate | Bleeding Index (BI) at Week 4 and Week 12 | BI at Week 12 (n=119, 119) | 0.43 score on a scale | Standard Error 0.01 |
Secondary
Modified Gingival Index (MGI) at Week 4 and Week 12
MGI was assessed on facial and lingual surfaces at two sites on each tooth (papillae and margin). The scoring of the MGI was performed under dental office conditions using a standard dental light for illuminating the oral cavity. This procedure was performed by a single examiner. The MGI scoring system is as follows: 0 = absence of inflammation; 1 = mild inflammation; slight change in color, little change in color; little change in texture of any portion of the marginal or papillary gingival unit; 2 = mild inflammation; criteria as above but involving the entire marginal or papillar gingival units; 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.
Time frame: Week 4, Week 12
Population: Intent to treat (ITT) population which included all participants who were randomized, received at least one dose of study product and had at least one post-baseline efficacy measurement. Number of participants analyzed is the number of participants from ITT population evaluated for this outcome at specific time points for respective treatment arm.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Stannous Fluoride | Modified Gingival Index (MGI) at Week 4 and Week 12 | MGI at Week 4 | 2.27 score on a scale | Standard Error 0.01 |
| Stannous Fluoride | Modified Gingival Index (MGI) at Week 4 and Week 12 | MGI at Week 12 | 2.29 score on a scale | Standard Error 0.01 |
| Sodium Monofluorophosphate | Modified Gingival Index (MGI) at Week 4 and Week 12 | MGI at Week 4 | 2.40 score on a scale | Standard Error 0.01 |
| Sodium Monofluorophosphate | Modified Gingival Index (MGI) at Week 4 and Week 12 | MGI at Week 12 | 2.47 score on a scale | Standard Error 0.01 |
Secondary
Number of Bleeding Sites at Week 4
Number of bleeding sites was measured as BI via a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 mm into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI was assessed on the facial and lingual gingival surfaces of each scorable tooth (7-7 in each arch). The BI scoring system used to measure bleeding sites is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed. Bleeding sites were assessed as the number of bleeding sites with a BI score of 1 or 2.
Time frame: Week 4
Population: Intent to treat (ITT) population which included all participants who were randomized, received at least one dose of study product and had at least one post-baseline efficacy measurement. Number of participants analyzed is the number of participants from ITT population evaluated for this outcome at Week 4 for respective treatment arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stannous Fluoride | Number of Bleeding Sites at Week 4 | 45.44 number of bleeding sites | Standard Error 1.92 |
| Sodium Monofluorophosphate | Number of Bleeding Sites at Week 4 | 68.30 number of bleeding sites | Standard Error 1.91 |
Secondary
Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12
Visible blood in expectorate for each participant was classified as (i) Present (Trace or Substantial) (ii) Absent. The number of participants with blood 'Present' (Trace or Substantial) or 'absent' in expectorate was analyzed.
Time frame: Week 4, Week 12
Population: Intent to treat (ITT) population which included all participants who were randomized, received at least one dose of study product and had at least one post-baseline efficacy measurement. Number of participants analyzed is the number of participants from ITT population evaluated for this outcome at specific time points for respective treatment arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Present | 92 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Trace | 35 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Substantial | 57 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Absent | 30 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Present | 72 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Trace | 18 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Substantial | 54 number of participants |
| Stannous Fluoride | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Absent | 47 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Absent | 41 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Present | 89 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Present | 78 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Trace | 31 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Substantial | 65 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Substantial | 58 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 12, Visible blood= Trace | 13 number of participants |
| Sodium Monofluorophosphate | Number of Participants With Visible Blood in Expectorate (Presence [Trace, Substantial]/Absence) at Week4 and Week 12 | At Week 4, Visible blood= Absent | 34 number of participants |