Trial Outcomes & Findings for Clinical Study to Investigate the Tooth Stain Removal Efficacy of Two Experimental Toothpastes Compared to a Standard Toothpaste When Used Twice Daily for 8 Weeks (NCT NCT05459558)

Last Updated: 2024-04-12

Results Overview

Extrinsic dental stain area and its intensity were assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. MLSI score= Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain were scored separately for each tooth on the scale 0 to 3, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. MLSI score ranged from 0 to 9. Mean Total MLSI Score = Mean of MLSI score across all evaluable tooth surfaces for the participant with a range from 0 to 9, where a lower score indicated an improvement. Change from Baseline was calculated by subtracting the Baseline value from the Week 8 value.

Recruitment status

COMPLETED

Study phase

Target enrollment

280 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2024-04-12

Participant Flow

The study was conducted at a single center in the United States of America.

A total of 281 participants were screened, 280 participants were enrolled, and 279 participants were randomized to a treatment (93 participants in Experimental Dentifrice 1, 92 participants in Experimental Dentifrice 2, and 94 participants in the Reference Dentifrice groups). A total of 272 randomized participants completed the study.

Participant milestones

Participant milestones
Measure	Experimental Dentifrice 1 Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5 percent \[%\] potassium nitrate \[KNO3\] dentifrice with 1% alumina and 5% sodium tripolyphosphate \[STP\]), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Overall Study STARTED	93	92	94
Overall Study COMPLETED	92	91	89
Overall Study NOT COMPLETED	1	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental Dentifrice 1 Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5 percent \[%\] potassium nitrate \[KNO3\] dentifrice with 1% alumina and 5% sodium tripolyphosphate \[STP\]), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Overall Study Adverse Event	1	0	0
Overall Study Scheduling issue	0	1	3
Overall Study Withdrawal by Subject	0	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.	Total n=273 Participants Total of all reporting groups
Age, Continuous	43.4 years STANDARD_DEVIATION 13.92 • n=5 Participants	39.5 years STANDARD_DEVIATION 13.73 • n=7 Participants	40.5 years STANDARD_DEVIATION 13.98 • n=5 Participants	41.2 years STANDARD_DEVIATION 13.92 • n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	50 Participants n=7 Participants	59 Participants n=5 Participants	161 Participants n=4 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	41 Participants n=7 Participants	31 Participants n=5 Participants	112 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants n=5 Participants	84 Participants n=7 Participants	80 Participants n=5 Participants	246 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	7 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	81 Participants n=5 Participants	83 Participants n=7 Participants	79 Participants n=5 Participants	243 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

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

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=89 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean Total Modified Lobene Stain Index (MLSI) Score at Week 8	-2.33 score on a scale Standard Error 0.048	-2.42 score on a scale Standard Error 0.049	-0.38 score on a scale Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: mITT Population.

Extrinsic dental stain area and its intensity were assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. MLSI score = Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain were scored separately for each tooth on the scale 0 to 3, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. MLSI score ranged from 0 to 9. Mean Total MLSI Score = Mean of MLSI score across all evaluable tooth surfaces for the participant with a range from 0 to 9, where a lower score indicated an improvement. Change from Baseline was calculated by subtracting the Baseline value from the Week 4 value.

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean Total MLSI Score at Week 4	-1.94 score on a scale Standard Error 0.046	-1.93 score on a scale Standard Error 0.046	-0.19 score on a scale Standard Error 0.047

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8

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

Extrinsic dental stain area and its intensity were assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. MLSI score = Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain were scored separately for each tooth on the scale 0 to 3, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. MLSI score ranged from 0 to 9. Mean Total MLSI Score = Mean of MLSI score across all evaluable tooth surfaces for the participant with a range from 0 to 9, where a lower score indicated an improvement. Change from Baseline was calculated by subtracting the Baseline value from the value at indicated timepoints.

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean Total MLSI Score at Weeks 4 and 8 Week 4	-1.94 score on a scale Standard Error 0.046	-1.93 score on a scale Standard Error 0.046	-0.19 score on a scale Standard Error 0.047
Change From Baseline in Mean Total MLSI Score at Weeks 4 and 8 Week 8	-2.33 score on a scale Standard Error 0.048	-2.42 score on a scale Standard Error 0.049	-0.38 score on a scale Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8

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

Tooth shade (color) of the facial surfaces of the four central and lateral maxillary incisors was assessed by a trained clinical examiner using the VITA Bleached guide 3D-MASTER. It used a value-ranked ordered scale from 1 (the lightest) to 29 (the darkest). The shade level of each tooth surface was scored visually by the clinical examiner with reference to the Bleached guide, where lower score indicated improvement. Change from Baseline was calculated by subtracting the Baseline value from the value at indicated timepoints.

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean VITA Shade Score (Examiner Assessed) at Weeks 4 and 8 Week 4	-0.81 score on a scale Standard Error 0.068	-0.59 score on a scale Standard Error 0.068	0.01 score on a scale Standard Error 0.069
Change From Baseline in Mean VITA Shade Score (Examiner Assessed) at Weeks 4 and 8 Week 8	-1.73 score on a scale Standard Error 0.134	-1.85 score on a scale Standard Error 0.134	-0.04 score on a scale Standard Error 0.136

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8

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

Extrinsic dental stain area and its intensity were assessed at the specific tooth sites (Gingival site: Crescent-shaped band, adjacent to the free margin of the gingiva and extending to the crest of the interdental papillae of the adjacent teeth. Body Site: The remainder of the tooth surface). MLSI score= Area score multiplied by Intensity score. Area and intensity of extrinsic dental stain was scored separately for each tooth on the scale 0 to 3, where 0= area with no stain, 1= Stain covering up to one third area and light intensity stain, 2= Stain covering up to two thirds area and moderate intensity stain, 3= Stain covering more than two thirds area and heavy intensity stain. MLSI score ranged from 0 to 9. Mean Total MLSI Score= Mean of MLSI score across all evaluable tooth surfaces for the participant with a range from 0 to 9, where a lower score indicated an improvement. Change from Baseline was calculated by subtracting the Baseline value from the value at indicated timepoints.

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Gingival Sites, Week 8	-2.96 score on a scale Standard Error 0.067	-3.09 score on a scale Standard Error 0.067	-0.46 score on a scale Standard Error 0.068
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Interproximal Sites, Week 4	-2.27 score on a scale Standard Error 0.055	-2.25 score on a scale Standard Error 0.056	-0.20 score on a scale Standard Error 0.056
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Body Sites, Week 8	-0.95 score on a scale Standard Error 0.043	-0.96 score on a scale Standard Error 0.043	-0.26 score on a scale Standard Error 0.043
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Gingival Sites, Week 4	-2.39 score on a scale Standard Error 0.064	-2.40 score on a scale Standard Error 0.065	-0.17 score on a scale Standard Error 0.065
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Interproximal Sites, Week 8	-2.69 score on a scale Standard Error 0.057	-2.81 score on a scale Standard Error 0.057	-0.40 score on a scale Standard Error 0.058
Change From Baseline in Mean Total MLSI Score in Gingival Sites, Interproximal Sites and Body Sites at Weeks 4 and 8 Body Sites, Week 4	-0.82 score on a scale Standard Error 0.046	-0.84 score on a scale Standard Error 0.047	-0.20 score on a scale Standard Error 0.047

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8

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

Extrinsic dental stain area and its intensity were assessed on the facial surfaces of the 6 maxillary and 6 mandibular anterior teeth and the lingual surfaces of the 6 mandibular anterior teeth. Area and intensity of extrinsic dental stain were scored separately for each tooth on the scale 0 to 3, where 0= area with no stain, 1= Stain covering up to one third of area and light intensity stain, 2= Stain covering up to two thirds of area and moderate intensity stain, 3= Stain covering more than two thirds of area and heavy intensity stain. Thus, MLSI score for both Area and Intensity ranged from 0 to 3, where lower score indicated improvement. Change from Baseline was calculated by subtracting the Baseline value from the value at indicated timepoints.

Outcome measures

Outcome measures
Measure	Experimental Dentifrice 1 n=92 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5% KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=91 Participants Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=90 Participants Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Change From Baseline in Mean MLSI (Area) and MLSI (Intensity) at Weeks 4 and 8 Area, Week 8	-1.24 score on a scale Standard Error 0.026	-1.30 score on a scale Standard Error 0.026	-0.16 score on a scale Standard Error 0.026
Change From Baseline in Mean MLSI (Area) and MLSI (Intensity) at Weeks 4 and 8 Area, Week 4	-0.98 score on a scale Standard Error 0.028	-0.96 score on a scale Standard Error 0.028	-0.09 score on a scale Standard Error 0.028
Change From Baseline in Mean MLSI (Area) and MLSI (Intensity) at Weeks 4 and 8 Intensity, Week 4	-0.96 score on a scale Standard Error 0.023	-0.96 score on a scale Standard Error 0.023	-0.09 score on a scale Standard Error 0.023
Change From Baseline in Mean MLSI (Area) and MLSI (Intensity) at Weeks 4 and 8 Intensity, Week 8	-1.16 score on a scale Standard Error 0.024	-1.21 score on a scale Standard Error 0.025	-0.19 score on a scale Standard Error 0.025

Adverse Events

Experimental Dentifrice 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Experimental Dentifrice 2

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Reference Dentifrice

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Haleon Response Center

HALEON

Phone: +447880182593

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	Experimental Dentifrice 1 n=93 participants at risk Randomized participants were instructed to brush their teeth with the experimental dentifrice 1 (5 % KNO3 dentifrice with 1% alumina and 5% STP), twice daily (morning and evening) for 2 minutes for 8 weeks.	Experimental Dentifrice 2 n=92 participants at risk Randomized participants were instructed to brush their teeth with the experimental dentifrice 2 (5% KNO3 dentifrice with 1% alumina, 5% STP and 2% high cleaning silica), twice daily (morning and evening) for 2 minutes for 8 weeks.	Reference Dentifrice n=94 participants at risk Randomized participants were instructed to brush their teeth with the reference dentifrice (Regular Fluoride Dentifrice), twice daily (morning and evening) for 2 minutes for 8 weeks.
Gastrointestinal disorders ANGULAR CHEILITIS	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders CHAPPED LIPS	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders GINGIVAL PAIN	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders GINGIVAL SWELLING	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders LIP DRY	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders LIP EXFOLIATION	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders LIP PAIN	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders LIP ULCERATION	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Gastrointestinal disorders ORAL MUCOSAL EXFOLIATION	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Nervous system disorders HEADACHE	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Nervous system disorders MIGRAINE	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
General disorders PYREXIA	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Immune system disorders SEASONAL ALLERGY	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Injury, poisoning and procedural complications TRAUMATIC ULCER	1.1% 1/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Psychiatric disorders ANXIETY	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Skin and subcutaneous tissue disorders ERYTHEMA	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).
Skin and subcutaneous tissue disorders SKIN FISSURES	0.00% 0/93 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	1.1% 1/92 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).	0.00% 0/94 • From screening (visit 1) until 5 days following last administration of the study product or last procedure (for approximately 64 days). An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study product including any washout or lead-in product (or medical device).