Trial Outcomes & Findings for A Clinical Study to Evaluate the Efficacy of a Stannous Fluoride Toothpaste for the Relief of Dentine Hypersensitivity in a Chinese Population (NCT NCT05750745)

Last Updated: 2024-11-20

Results Overview

Schiff sensitivity score was assessed by participant's response to an evaporative (air) stimulus after the stimulation of the 2 test teeth selected at Baseline by the examiner. Participant's response was scored using Schiff sensitivity scale, an examiner-based index, scored immediately following administration of the evaporative (air) stimulus. Score ranged from 0-3 where 0=Participant did not respond to air stimulation; 1=Participant responded to air stimulus but did not request discontinuation of stimulus; 2=Participant responded to air stimulus and requested discontinuation or moved from stimulus; 3=Participant responded to stimulus, considered stimulus to be painful, and requested discontinuation of the stimulus. Higher score indicated worse outcome (more sensitivity). Change from Baseline was calculated by subtracting the Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A negative change from Baseline indicated improvement in sensitivity.

Recruitment status

COMPLETED

Study phase

Target enrollment

416 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2024-11-20

Participant Flow

This study was conducted at a single center in China.

A total of 720 participants were screened of which 416 participants were enrolled and 243 participants were randomized to receive treatment in 3 groups - Test group (97 participants), Positive Control group (50 participants) and Negative Control group (96 participants). A total of 240 randomized participants completed the study.

Participant milestones

Participant milestones
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454 percent (%) weight by weight (w/w) Stannous fluoride (SnF2) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 milliliters (mL) of water using the measuring cup provided.	Positive Control (Sensodyne Repair and Protect) Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Repair and Protect toothpaste containing 5.0% w/w Calcium sodium phosphosilicate (CSPS) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Overall Study STARTED	97	50	96
Overall Study COMPLETED	95	49	96
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454 percent (%) weight by weight (w/w) Stannous fluoride (SnF2) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 milliliters (mL) of water using the measuring cup provided.	Positive Control (Sensodyne Repair and Protect) Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Repair and Protect toothpaste containing 5.0% w/w Calcium sodium phosphosilicate (CSPS) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Overall Study Adverse Event	1	0
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

A Clinical Study to Evaluate the Efficacy of a Stannous Fluoride Toothpaste for the Relief of Dentine Hypersensitivity in a Chinese Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10mL of water using the measuring cup provided.	Positive Control (Sensodyne Repair and Protect) n=49 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Repair and Protect toothpaste containing 5.0% w/w CSPS for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Total n=240 Participants Total of all reporting groups
Age, Continuous	42.4 years STANDARD_DEVIATION 7.64 • n=5 Participants	43.7 years STANDARD_DEVIATION 7.55 • n=7 Participants	43.2 years STANDARD_DEVIATION 7.57 • n=5 Participants	43.0 years STANDARD_DEVIATION 7.58 • n=4 Participants
Sex: Female, Male Female	89 Participants n=5 Participants	47 Participants n=7 Participants	88 Participants n=5 Participants	224 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	95 Participants n=5 Participants	49 Participants n=7 Participants	96 Participants n=5 Participants	240 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: mITT population.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Week 12 (Test Dentifrice Versus [vs.] Negative Control)	-0.90 score on a scale Standard Error 0.068	-0.74 score on a scale Standard Error 0.068

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: mITT population.

Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe). The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine. After each application of the stimulus, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting with two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline, the upper force setting was 20 g. Tactile threshold (g) was derived as the mean value for the two 'Test Teeth' selected by the examiner at Baseline. Higher tactile threshold indicated better outcome (less sensitivity). Change from Baseline was calculated by subtracting Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A positive change from Baseline indicated an improvement in sensitivity.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Tactile Threshold (Gram [g]) (Average of the Two Selected Test Teeth) at Week 12 (Test Dentifrice vs. Negative Control)	25.86 grams Standard Error 3.008	19.65 grams Standard Error 2.977

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: mITT population.

Evaporative (air) sensitivity was assessed on the facial surfaces of the two test teeth selected by the examiner at Baseline by directing a 1 second application of air from standard dental syringe held perpendicular to tooth surface. Participant's response to the stimulus was evaluated using Schiff sensitivity scale with scores ranging from 0 (Participant did not respond to air stimulation) to 3 (Responded to stimulus, considered stimulus to be painful, requested discontinuation of the stimulus). Participants then rated the intensity of their response to the evaporative (air) stimulus using a 100 mm VAS with scores ranging from 0 mm (No discomfort) to 100 mm (Extreme discomfort; worst imaginable). Higher score indicated worse outcome (higher sensitivity). Change from Baseline was calculated by subtracting Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A negative change from Baseline indicated an improvement in sensitivity.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Visual Analog Scale (VAS) Score (Millimeters [mm]) (Average of the Two Selected Test Teeth) at Week 12 (Test Dentifrice vs. Negative Control)	-38.84 score on a scale Standard Error 2.872	-33.02 score on a scale Standard Error 2.830

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: mITT population. Only those participants with data available at the indicated timepoint were analyzed.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=93 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Week 6 (Test Dentifrice vs. Negative Control)	-0.51 score on a scale Standard Error 0.049	-0.38 score on a scale Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: mITT population. Only those participants with data available at the indicated timepoint were analyzed.

Tactile sensitivity was assessed for eligible incisor, canine and pre-molar teeth using a constant pressure probe (Yeaple probe). The probe tip was placed perpendicular to the facial surface of tooth and drawn slowly across the exposed dentine. After each application, the participant was asked to indicate whether they experienced any pain or discomfort (yes/no response). The pressure setting with two consecutive 'yes' responses was recorded as the tactile threshold (g). At Baseline, the upper force setting was 20 g. Tactile threshold (g) was derived as the mean value for the two 'Test Teeth' selected by the examiner at Baseline. Higher tactile threshold indicated better outcome (less sensitivity). Change from Baseline was calculated by subtracting Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A positive change from Baseline indicated an improvement in sensitivity.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=93 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Tactile Threshold (g) (Average of the Two Selected Test Teeth) at Week 6 (Test Dentifrice vs. Negative Control)	11.74 grams Standard Error 2.393	9.36 grams Standard Error 2.357

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: mITT population. Only those participants with data available at the indicated timepoint were analyzed.

Evaporative (air) sensitivity was assessed on the facial surfaces of the two test teeth selected by the examiner at Baseline by directing a 1 second application of air from standard dental syringe held perpendicular to tooth surface. Participant's response to the stimulus was evaluated using Schiff sensitivity scale with scores ranging from 0 (Participant did not respond to air stimulation) to 3 (Responded to stimulus, considered stimulus to be painful, requested discontinuation of the stimulus). Participant then rated the intensity of their response to the evaporative (air) stimulus using a 100 mm VAS with scores ranging from 0 mm (No discomfort) to 100 mm (Extreme discomfort; worst imaginable). Higher score indicated worse outcome (higher sensitivity). Change from Baseline was calculated by subtracting Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A negative change from Baseline indicated an improvement in sensitivity.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=93 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=95 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in VAS Score (mm) (Average of the Two Selected Test Teeth) at Week 6 (Test Dentifrice vs. Negative Control)	-21.92 score on a scale Standard Error 2.603	-16.28 score on a scale Standard Error 2.556

SECONDARY outcome

Timeframe: Baseline, Week 6 and Week 12

Population: mITT population. Only those participants with data available at the indicated timepoints were analyzed.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=49 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 6	-0.36 score on a scale Standard Error 0.069	-0.38 score on a scale Standard Error 0.049
Adjusted Mean Change From Baseline in Schiff Sensitivity Score (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 12	-0.67 score on a scale Standard Error 0.095	-0.74 score on a scale Standard Error 0.068

SECONDARY outcome

Timeframe: Baseline, Week 6 and Week 12

Population: mITT population. Only those participants with data available at the indicated timepoints were analyzed.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=49 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in Tactile Threshold (g) (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 6	6.77 grams Standard Error 2.883	9.36 grams Standard Error 2.357
Adjusted Mean Change From Baseline in Tactile Threshold (g) (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 12	18.53 grams Standard Error 3.830	19.65 grams Standard Error 2.977

SECONDARY outcome

Timeframe: Baseline, Week 6 and Week 12

Population: mITT population. Only those participants with data available at the indicated timepoints were analyzed.

Evaporative (air) sensitivity was assessed on the facial surfaces of the two test teeth selected by the examiner at Baseline by directing a 1 second application of air from standard dental syringe held perpendicular to tooth surface. Participant's response to the stimulus was evaluated using Schiff sensitivity scale with scores ranging from 0(Participant did not respond to air stimulation) to 3(Responded to stimulus, considered stimulus to be painful, requested discontinuation of the stimulus). Participant then rated the intensity of their response to the evaporative (air) stimulus using a 100 mm VAS with scores ranging from 0 mm (No discomfort) to 100 mm (Extreme discomfort; worst imaginable). Higher score indicated worse outcome (higher sensitivity). Change from Baseline was calculated by subtracting Baseline value from the value at indicated timepoint. Baseline was defined as Day 1 value. A negative change from Baseline indicated an improvement in sensitivity.

Outcome measures

Outcome measures
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=49 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 Participants Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Adjusted Mean Change From Baseline in VAS Score (mm) (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 6	-15.53 score on a scale Standard Error 3.123	-16.28 score on a scale Standard Error 2.556
Adjusted Mean Change From Baseline in VAS Score (mm) (Average of the Two Selected Test Teeth) at Week 6 and Week 12 (Positive Control vs. Negative Control) Change from Baseline at Week 12	-29.30 score on a scale Standard Error 3.542	-33.02 score on a scale Standard Error 2.830

Adverse Events

Test Dentifrice (Sensodyne Sensitivity and Gum)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Positive Control (Sensodyne Repair and Protect)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Negative Control (Crest Cavity Protection Fresh Lime)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Haleon Response Center

HALEON

Phone: +441932959500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee HALEON agreements may vary with individual investigators but will not prohibit any investigator from publishing. HALEON supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Test Dentifrice (Sensodyne Sensitivity and Gum) n=97 participants at risk Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Sensitivity and Gum toothpaste containing 0.454% w/w SnF2 for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Positive Control (Sensodyne Repair and Protect) n=50 participants at risk Participants brushed the two test teeth first, then the whole mouth (all teeth) with Sensodyne Repair and Protect toothpaste containing 5.0% w/w CSPS for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.	Negative Control (Crest Cavity Protection Fresh Lime) n=96 participants at risk Participants brushed the two test teeth first, then the whole mouth (all teeth) with Crest Cavity Protection Fresh Lime toothpaste (regular fluoride toothpaste) for 1-timed minute, twice daily (morning and evening) for up to 12 weeks. After brushing, participants rinsed once with 10 mL of water using the measuring cup provided.
Gastrointestinal disorders LIP ULCERATION	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.1% 2/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders MOUTH ULCERATION	3.1% 3/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders ANGULAR CHEILITIS	2.1% 2/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders ORAL BLOOD BLISTER	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.1% 2/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders CHEILITIS	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders DENTAL CARIES	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders ORAL CAVITY FISTULA	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders ORAL MUCOSAL BLISTERING	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Gastrointestinal disorders TONGUE ULCERATION	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Injury, poisoning and procedural complications MOUTH INJURY	3.1% 3/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	4.0% 2/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Injury, poisoning and procedural complications FACE INJURY	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	4.0% 2/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Injury, poisoning and procedural complications LIP INJURY	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Injury, poisoning and procedural complications PALATE INJURY	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Injury, poisoning and procedural complications TOOTH FRACTURE	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations GINGIVITIS	2.1% 2/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations GINGIVAL ABSCESS	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations ABSCESS ORAL	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations HERPES SIMPLEX	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations NASOPHARYNGITIS	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Infections and infestations PERIODONTITIS	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
General disorders MUCOSAL INFLAMMATION	1.0% 1/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
General disorders OEDEMA MUCOSAL	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MELANOCYTIC NAEVUS	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	2.0% 1/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.
Skin and subcutaneous tissue disorders BLOOD BLISTER	0.00% 0/97 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	0.00% 0/50 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.	1.0% 1/96 • From signing of the informed consent form until 5 days following the last administration of the study product or last study procedure (up to approximately 123 days). An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product. All-Cause Mortality included all randomized participants. Serious and Other AEs: Safety population included all participants who completed at least one use of study product.