Benzocaine Gel Toothache Dose-Response Study

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00474175
• Collaborator: Church & Dwight Company, Inc. (Industry), Consumer Healthcare Products Association (Other)
• Enrollment: 577
• Locations: 8
• Arms: 3
• Duration (Months): 43
• Patients Per Site: 72.1
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of benzocaine gel products for the relief of toothache and to assess the subject's compliance with proposed label directions.

Condition or Disease	Intervention/Treatment	Phase
Toothache	Drug: Placebo gel; Drug: benzocaine; Drug: benzocaine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 577 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Benzocaine Gel Toothache Dose-Response Study
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Placebo control	Drug: Placebo gel; single dose (less than 1g) of a matching placebo gel
Active Comparator: 2 10% benzocaine gel formulation	Drug: benzocaine; single dose (less than 1g) of 10% benzocaine gel formulation
Active Comparator: 3 20% benzocaine gel formulation	Drug: benzocaine; single dose (less than 1g) of 20% benzocaine gel formulation

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Response [Baseline, 5, 10, 15 and 20 minutes]

   Responder was defined as participant experiencing improvement in pain intensity, as exhibited by a pain score reduction on the Dental Pain Scale (DPS) from baseline of at least 1 unit for two consecutive assessments anytime between the 5 and 20-minute time points. Response in DPS scale was assigned values as 0 (None), 1 (Mild), 2 (Moderate) and 3 (Severe).

Secondary Outcome Measures

1. Time to First Confirmed Perceptible Relief [0 to 120 minutes]

   Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment they first began to experience any relief. Stopwatch was active up to 120 minutes after dosing or until stopped by the participant, or rescue medication was administered.

2. Time to Meaningful Relief [0 to 120 minutes]

   Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment they first began to experience meaningful relief. Stopwatch was active up to 120 minutes after dosing or until stopped by the participant, or rescue medication was administered.

3. Duration of Effect [0 to 120 minutes]

   Duration of effect was defined as the time difference between onset of effect and its offset. Onset of effect was the first time point at which two consecutive pain scores less severe than at baseline by at least 1 unit (on the DPS) were attained. Offset of effect was the first of the following events to occur after onset: time to drop out if the drop out was due to lack of efficacy, time of rescue medication, or the first time point following onset of effect at which two consecutive pain scores that are at least as severe as at baseline were attained.

4. Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores [60 minutes and 120 minutes]

   SPRID is time-weighted sum of pain relief scores combined with pain intensity difference (PRID) scores over 60 and 120 minutes. SPRID score range was 0 (worst) to 7 (best) for SPRID 60 and 0 (worst) to 14 (best) for SPRID 120. PRID is sum of Pain intensity differences (PID) and Dental pain relief scale (DPRS) scores at each post-dosing time point. PID was calculated as baseline DPS minus DPS score at given time point (DPS range: 0 [none] to 3 [severe]; baseline DPS range from 2-3). PID score ranges from -1 (worst) to 3 (best). DPRS is 5-point scale ranging from 0 (No-relief) to 4 (Complete).

5. Time to Dropping Out Due to Lack of Efficacy or Rescue Medication [0 to 120 minutes]

   Median time of dropping out of the participants from the study due to lack of efficacy or rescue medication (ibuprofen 200-400 mg or acetaminophen 1000 mg), whichever comes first.

6. Pain Relief Combined With Pain Intensity Difference (PRID) Scores [5 to 120 minutes]

   PRID is sum of PID and DPRS scores at each post-dosing time point. The overall possible score range, for PRID is -1 (worst) to 7 (best). PID was calculated as baseline DPS minus DPS score at given time point (DPS range from 0 [none] to 3 [severe]; baseline DPS range from 2-3). PID score ranges from -1 (worst) to 3 (best). DPRS is 5-point scale ranging from 0 (No-relief) to 4 (Complete).

7. Global Satisfaction Assessment [120 minutes]

   Participants were asked to provide an overall assessment of their satisfaction with the study medication on a categorical scale. Response in this scale was assigned values as 0 (Poor), 1 (Fair), 2 (Good), 3 (Very Good) and 4 (Excellent).

Other Outcome Measures

1. Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied [Baseline and 5 minutes]

   Amount of study medication applied was calculated by weighing medication tube prior and post-dosing.

2. Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication [Baseline and 5 minutes]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females at least 12 years of age.

• Presence of spontaneous toothache pain in only one permanent tooth. Toothache pain is due only to an open tooth cavity and only as a result of dental caries, loss of a restoration or tooth fracture.

• To qualify for the study, the subject must have a rating of at least moderate pain on the Dental Pain Scale (DPS) and a score of at least 50 mm on the Visual Analog Scale. To be included in the moderate pain stratum, the subjects must have a rating of moderate pain in the DPS and to be included in the severe pain stratum the subjects must have a rating of severe pain in the DPS.

• Females who are neither pregnant, as verified by a urine-based pregnancy test, nor breast-feeding.

• Female subjects of childbearing potential and those who are post-menopausal for less than 2 years must be using a medically approved method of contraception (i.e., oral, transdermal or implanted contraceptive devices, intrauterine device, diaphragm, condom, abstinence, or surgical sterility).

• Subjects must be reliable, cooperative and of adequate intelligence to read and understand the rating scales and other study instructions.

• Subjects must be able to read, comprehend, and sign the consent form. Minors will provide assent to study participation if age appropriate. Parent/legal guardian must be able to read, comprehend, and sign the informed consent form.

Exclusion Criteria:

• Presence of spontaneous toothache pain in a primary tooth. Presence of spontaneous toothache pain in more than one tooth. Presence of an open tooth cavity in a tooth adjacent to the painful tooth with the open tooth cavity.

• Presence of concomitant oral pain due to any other condition such as: soft-tissue lesions (e.g., aphthous or traumatic ulcer, herpes labialis, acute necrotizing ulcerative gingivitis); or multiple hard-tissue (e.g., carious) lesions; pain due to other surgical procedures, injuries or dental surface sensitivity.

• Presence of a periodontal abscess as diagnosed from an X-ray or clinical examination of the painful tooth.

• Presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• History of acute or chronic hemolytic anemia.

• History of sensitivity or allergy to benzocaine or other local anesthetic agents.

• Use of any short-acting oral or topical analgesic/ anesthetic product within 2 hours of enrollment or any long-acting Rx or OTC analgesic product within 4 hours of enrollment.

• Use of an investigational drug or participation in an investigational study within the past 30 days.

• Previous participation in this study.

• Member or a relative of the study site staff or sponsor directly involved in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Baltimore	Maryland	United States	21201
2	Pfizer Investigational Site	Boston	Massachusetts	United States	02111-1527
3	Pfizer Investigational Site	Detroit	Michigan	United States	48207
4	Pfizer Investigational Site	Buffalo	New York	United States	14214-3008
5	Pfizer Investigational Site	New York	New York	United States	10010
6	Pfizer Investigational Site	Columbus	Ohio	United States	43205-2696
7	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19104-6030
8	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15261-0001

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer
• Church & Dwight Company, Inc.
• Consumer Healthcare Products Association

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00474175
• Other Study ID Numbers: BZ-03-07; NCT00836511
• First Posted: May 16, 2007
• Last Update Posted: Feb 28, 2013
• Last Verified: Feb 1, 2013

• Additional relevant MeSH terms: Toothache; Benzocaine

Study Results

Participant Flow

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Period Title: Overall Study
STARTED	115	233	229
Treated	115	233	228
COMPLETED	114	226	225
NOT COMPLETED	1	7	4

Baseline Characteristics

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%	Total
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.	Total of all reporting groups
Overall Participants	115	233	228	576
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.2 (12.6)	30.8 (12.7)	31.3 (12.8)	31.1 (12.7)
Sex: Female, Male (Count of Participants)
Female	62 53.9%	120 51.5%	118 51.8%	300 52.1%
Male	53 46.1%	113 48.5%	110 48.2%	276 47.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Response
Description	Responder was defined as participant experiencing improvement in pain intensity, as exhibited by a pain score reduction on the Dental Pain Scale (DPS) from baseline of at least 1 unit for two consecutive assessments anytime between the 5 and 20-minute time points. Response in DPS scale was assigned values as 0 (None), 1 (Mild), 2 (Moderate) and 3 (Severe).
Time Frame	Baseline, 5, 10, 15 and 20 minutes

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Number [Percentage of participants]	70.4 61.2%	80.7 34.6%	87.3 38.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	P-value was calculated using Cochran-Mantel-Haenszel (CMH) test which was adjusted for site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and its associated confidence interval (C.I.) was calculated based on CMH weighted percentages and the corresponding standard error.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Alternative hypotheses tested in the study was that benzocaine 20% was significantly (p less than or equal to [=<] 0.05) more effective than placebo.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	16.46
	Confidence Interval	(2-Sided) 95%; 7.2 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	P-value was calculated using CMH test which was adjusted for site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and its associated C.I. was calculated based on CMH weighted percentages and the corresponding standard error.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments	Alternative hypotheses tested in the study was that benzocaine 10% was significantly (p=<0.05) more effective than placebo provided that benzocaine 20% was more effective than placebo.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	9.80
	Confidence Interval	(2-Sided) 95%; 0.3 to 19.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	P-value was calculated using CMH test which was adjusted for site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and its associated C.I. was calculated based on CMH weighted percentages and the corresponding standard error.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Dose response was considered established if the percentage of responders between the 20% and 10% was greater than or equal to 5%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	6.72
	Confidence Interval	(2-Sided) 95%; 0.2 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to First Confirmed Perceptible Relief
Description	Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment they first began to experience any relief. Stopwatch was active up to 120 minutes after dosing or until stopped by the participant, or rescue medication was administered.
Time Frame	0 to 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Median (95% Confidence Interval) [Minutes]	2.0	1.4	1.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. Hazard Ratio (HR) of Benzocaine 20% relative to the Placebo was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.02
	Confidence Interval	(2-Sided) 95%; 1.55 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. HR of Benzocaine 10% relative to the Placebo was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. HR of Benzocaine 20% relative to the Benzocaine 10% was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to Meaningful Relief
Description	Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment they first began to experience meaningful relief. Stopwatch was active up to 120 minutes after dosing or until stopped by the participant, or rescue medication was administered.
Time Frame	0 to 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Median (95% Confidence Interval) [Minutes]	8.5	4.4	3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. HR of Benzocaine 20% relative to the Placebo was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.04
	Confidence Interval	(2-Sided) 95%; 1.57 to 2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. HR of Benzocaine 10% relative to the Placebo was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.73
	Confidence Interval	(2-Sided) 95%; 1.34 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	P-value was calculated using Cox proportional hazard regression model which was adjusted for treatment, site and baseline DPS. HR of Benzocaine 20% relative to the Benzocaine 10% was calculated. C.I. was based on the Wald statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.100
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Effect
Description	Duration of effect was defined as the time difference between onset of effect and its offset. Onset of effect was the first time point at which two consecutive pain scores less severe than at baseline by at least 1 unit (on the DPS) were attained. Offset of effect was the first of the following events to occur after onset: time to drop out if the drop out was due to lack of efficacy, time of rescue medication, or the first time point following onset of effect at which two consecutive pain scores that are at least as severe as at baseline were attained.
Time Frame	0 to 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Median (95% Confidence Interval) [Minutes]	NA	NA	NA

5. Secondary Outcome

Title	Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores
Description	SPRID is time-weighted sum of pain relief scores combined with pain intensity difference (PRID) scores over 60 and 120 minutes. SPRID score range was 0 (worst) to 7 (best) for SPRID 60 and 0 (worst) to 14 (best) for SPRID 120. PRID is sum of Pain intensity differences (PID) and Dental pain relief scale (DPRS) scores at each post-dosing time point. PID was calculated as baseline DPS minus DPS score at given time point (DPS range: 0 [none] to 3 [severe]; baseline DPS range from 2-3). PID score ranges from -1 (worst) to 3 (best). DPRS is 5-point scale ranging from 0 (No-relief) to 4 (Complete).
Time Frame	60 minutes and 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
SPRID 60	3.1 (2.3)	3.4 (2.0)	3.6 (2.0)
SPRID 120	5.9 (4.8)	6.4 (4.2)	6.7 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	SPRID 60: P-value was calculated using Analysis of Variance (ANOVA) which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	SPRID 60: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.173
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	SPRID 60: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.358
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	SPRID 120: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.135
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.23 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	SPRID 120: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.332
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; -0.49 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	SPRID 120: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.517
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -0.53 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time to Dropping Out Due to Lack of Efficacy or Rescue Medication
Description	Median time of dropping out of the participants from the study due to lack of efficacy or rescue medication (ibuprofen 200-400 mg or acetaminophen 1000 mg), whichever comes first.
Time Frame	0 to 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Median (95% Confidence Interval) [Minutes]	NA	NA	NA

7. Secondary Outcome

Title	Pain Relief Combined With Pain Intensity Difference (PRID) Scores
Description	PRID is sum of PID and DPRS scores at each post-dosing time point. The overall possible score range, for PRID is -1 (worst) to 7 (best). PID was calculated as baseline DPS minus DPS score at given time point (DPS range from 0 [none] to 3 [severe]; baseline DPS range from 2-3). PID score ranges from -1 (worst) to 3 (best). DPRS is 5-point scale ranging from 0 (No-relief) to 4 (Complete).
Time Frame	5 to 120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
5 minutes	2.72 (2.05)	3.25 (1.98)	3.66 (1.87)
10 minutes	3.08 (2.25)	3.56 (2.00)	3.88 (1.97)
15 minutes	3.18 (2.46)	3.64 (2.23)	3.96 (2.07)
20 minutes	3.21 (2.50)	3.64 (2.27)	3.74 (2.23)
25 minutes	3.12 (2.53)	3.60 (2.25)	3.73 (2.27)
30 minutes	3.11 (2.65)	3.39 (2.32)	3.66 (2.38)
40 minutes	3.06 (2.60)	3.44 (2.39)	3.52 (2.43)
50 minutes	3.20 (2.68)	3.41 (2.40)	3.42 (2.45)
60 minutes	3.17 (2.74)	3.18 (2.47)	3.38 (2.57)
70 minutes	2.98 (2.75)	3.16 (2.49)	3.33 (2.59)
80 minutes	2.91 (2.77)	3.09 (2.55)	3.24 (2.60)
90 minutes	2.78 (2.70)	3.05 (2.63)	3.09 (2.61)
100 minutes	2.78 (2.70)	3.00 (2.62)	2.93 (2.58)
110 minutes	2.70 (2.71)	2.90 (2.60)	2.96 (2.59)
120 minutes	2.73 (2.72)	2.82 (2.61)	2.84 (2.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	5 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	5 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	5 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	10 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.33 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	10 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	10 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.119
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	15 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	15 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	15 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.131
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	20 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.01 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	20 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.099
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	20 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.647
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	25 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.08 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	25 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	25 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.551
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	30 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.01 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	30 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.316
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	30 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	40 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.099
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; -0.09 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	40 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.186
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	40 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	50 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.452
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	50 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.479
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	50 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	60 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.465
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	60 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.57 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	60 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.376
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	70 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	70 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.581
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	70 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.422
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	80 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.271
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	80 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.612
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	80 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.465
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	90 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	90 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	90 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.769
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	100 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.610
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	100 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.511
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	100 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.859
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.52 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	110 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.386
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	110 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.563
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	110 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.721
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	120 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.725
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.48 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	120 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 10% - Placebo) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.839
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.52 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	120 minutes: P-value was calculated using ANOVA which was adjusted for treatment, site and baseline DPS. Treatment difference (Benzocaine 20% - Benzocaine 10%) and corresponding 95% C.I. were calculated based on least-squares means from the ANOVA model with treatment, site, and baseline DPS effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.855
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Global Satisfaction Assessment
Description	Participants were asked to provide an overall assessment of their satisfaction with the study medication on a categorical scale. Response in this scale was assigned values as 0 (Poor), 1 (Fair), 2 (Good), 3 (Very Good) and 4 (Excellent).
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received study medication.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Mean (Standard Deviation) [Units on a scale]	2.1 (1.6)	2.5 (1.2)	2.5 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 20%
	Comments	P-value was calculated from the CMH test with modified ridit scores, adjusted for site baseline pain intensity. Treatment difference (Benzocaine 20% versus Placebo) and the associated confidence interval were calculated based on the weighted Gamma statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Benzocaine 10%
	Comments	P-value was calculated from the CMH test with modified ridit scores, adjusted for site baseline pain intensity. Treatment difference (Benzocaine 10% versus Placebo) and the associated confidence interval were calculated based on the weighted Gamma statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benzocaine 10%, Benzocaine 20%
	Comments	P-value was calculated from the CMH test with modified ridit scores, adjusted for site baseline pain intensity. Treatment difference (Benzocaine 20% versus Benzocaine 10%) and the associated confidence interval were calculated based on the weighted Gamma statistic.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments	The a priori threshold p-value was specified as 0.05, and no adjustments were made for multiple comparisons.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Other Pre-specified Outcome

Title	Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied
Description	Amount of study medication applied was calculated by weighing medication tube prior and post-dosing.
Time Frame	Baseline and 5 minutes

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication and had follow up data.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Mean (Standard Deviation) [Milligram (mg)]	258.6 (163.4)	226.8 (138.2)	233.1 (150.7)

10. Other Pre-specified Outcome

Title	Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication
Time Frame	Baseline and 5 minutes

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication and had follow up data.

Arm/Group Title	Placebo	Benzocaine 10%	Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.	Single dose of 10% benzocaine gel administered as per product label directions.	Single dose of 20% benzocaine gel administered as per product label directions.
Measure Participants	115	233	228
Number (95% Confidence Interval) [Percentage of participants]	83.5 72.6%	89.3 38.3%	89.5 39.3%

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Placebo		Benzocaine 10%		Benzocaine 20%
Arm/Group Description	Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions.		Single dose of 10% benzocaine gel administered as per product label directions.		Single dose of 20% benzocaine gel administered as per product label directions.
All Cause Mortality
	Placebo		Benzocaine 10%		Benzocaine 20%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Benzocaine 10%		Benzocaine 20%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/233 (0%)		0/228 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Benzocaine 10%		Benzocaine 20%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/115 (3.5%)		6/233 (2.6%)		6/228 (2.6%)
Eye disorders
Diplopia	0/115 (0%)		1/233 (0.4%)		0/228 (0%)
Gastrointestinal disorders
Eructation	0/115 (0%)		0/233 (0%)		1/228 (0.4%)
Stomach upset	0/115 (0%)		0/233 (0%)		1/228 (0.4%)
Toothache	1/115 (0.9%)		0/233 (0%)		0/228 (0%)
Infections and infestations
Post operation wound infection	1/115 (0.9%)		0/233 (0%)		0/228 (0%)
Tooth caries Not Otherwise Specified (NOS)	0/115 (0%)		1/233 (0.4%)		0/228 (0%)
Investigations
Blood pressure increased	0/115 (0%)		2/233 (0.9%)		1/228 (0.4%)
Nervous system disorders
Somnolence	1/115 (0.9%)		1/233 (0.4%)		1/228 (0.4%)
Dizziness	0/115 (0%)		0/233 (0%)		1/228 (0.4%)
Psychiatric disorders
Nervousness	0/115 (0%)		0/233 (0%)		1/228 (0.4%)
Respiratory, thoracic and mediastinal disorders
Hiccups	1/115 (0.9%)		0/233 (0%)		0/228 (0%)
Surgical and medical procedures
Tooth extraction	0/115 (0%)		1/233 (0.4%)		0/228 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Wyeth has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.