Toothache
Conditions
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.
Interventions
DRUGPlacebo gel
single dose (less than 1g) of a matching placebo gel
DRUGbenzocaine
single dose (less than 1g) of 10% benzocaine gel formulation
Sponsors
Church & Dwight Company, Inc.
Consumer Healthcare Products Association
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication | Baseline and 5 minutes | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single dose of placebo gel matched to either 10 % or 20 % benzocaine gel administered as per product label directions. | 115 |
| Benzocaine 10% Single dose of 10% benzocaine gel administered as per product label directions. | 233 |
| Benzocaine 20% Single dose of 20% benzocaine gel administered as per product label directions. | 228 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 0 | 1 | 0 |
| Overall Study | Ineligible | 1 | 3 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Benzocaine 10% | Benzocaine 20% | Total |
|---|---|---|---|---|
| Age Continuous | 31.2 Years STANDARD_DEVIATION 12.6 | 30.8 Years STANDARD_DEVIATION 12.7 | 31.3 Years STANDARD_DEVIATION 12.8 | 31.1 Years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 62 Participants | 120 Participants | 118 Participants | 300 Participants |
| Sex: Female, Male Male | 53 Participants | 113 Participants | 110 Participants | 276 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 115 | 6 / 233 | 6 / 228 |
| serious Total, serious adverse events | 0 / 115 | 0 / 233 | 0 / 228 |
Outcome results
Primary
Percentage of Participants With a Response
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
Population: Intent to treat (ITT) population included all randomized participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Response | 70.4 Percentage of participants |
| Benzocaine 10% | Percentage of Participants With a Response | 80.7 Percentage of participants |
| Benzocaine 20% | Percentage of Participants With a Response | 87.3 Percentage of participants |
Comparison: 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.p-value: <0.00195% CI: [7.2, 25.7]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.03895% CI: [0.3, 19.3]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.04795% CI: [0.2, 13.3]Cochran-Mantel-Haenszel
Secondary
Duration of Effect
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Effect | NA Minutes |
| Benzocaine 10% | Duration of Effect | NA Minutes |
| Benzocaine 20% | Duration of Effect | NA Minutes |
Secondary
Global Satisfaction Assessment
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Global Satisfaction Assessment | 2.1 Units on a scale | Standard Deviation 1.6 |
| Benzocaine 10% | Global Satisfaction Assessment | 2.5 Units on a scale | Standard Deviation 1.2 |
| Benzocaine 20% | Global Satisfaction Assessment | 2.5 Units on a scale | Standard Deviation 1.2 |
Comparison: 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.p-value: 0.03595% CI: [0.01, 0.33]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.03995% CI: [0, 0.33]Cochran-Mantel-Haenszel
Comparison: 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.p-value: 0.94495% CI: [-0.15, 0.13]Cochran-Mantel-Haenszel
Secondary
Pain Relief Combined With Pain Intensity Difference (PRID) Scores
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 30 minutes | 3.11 Units on a scale | Standard Deviation 2.65 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 15 minutes | 3.18 Units on a scale | Standard Deviation 2.46 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 80 minutes | 2.91 Units on a scale | Standard Deviation 2.77 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 40 minutes | 3.06 Units on a scale | Standard Deviation 2.6 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 10 minutes | 3.08 Units on a scale | Standard Deviation 2.25 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 70 minutes | 2.98 Units on a scale | Standard Deviation 2.75 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 50 minutes | 3.20 Units on a scale | Standard Deviation 2.68 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 100 minutes | 2.78 Units on a scale | Standard Deviation 2.7 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 60 minutes | 3.17 Units on a scale | Standard Deviation 2.74 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 20 minutes | 3.21 Units on a scale | Standard Deviation 2.5 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 120 minutes | 2.73 Units on a scale | Standard Deviation 2.72 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 5 minutes | 2.72 Units on a scale | Standard Deviation 2.05 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 25 minutes | 3.12 Units on a scale | Standard Deviation 2.53 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 110 minutes | 2.70 Units on a scale | Standard Deviation 2.71 |
| Placebo | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 90 minutes | 2.78 Units on a scale | Standard Deviation 2.7 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 90 minutes | 3.05 Units on a scale | Standard Deviation 2.63 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 5 minutes | 3.25 Units on a scale | Standard Deviation 1.98 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 10 minutes | 3.56 Units on a scale | Standard Deviation 2 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 15 minutes | 3.64 Units on a scale | Standard Deviation 2.23 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 20 minutes | 3.64 Units on a scale | Standard Deviation 2.27 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 25 minutes | 3.60 Units on a scale | Standard Deviation 2.25 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 30 minutes | 3.39 Units on a scale | Standard Deviation 2.32 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 40 minutes | 3.44 Units on a scale | Standard Deviation 2.39 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 50 minutes | 3.41 Units on a scale | Standard Deviation 2.4 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 60 minutes | 3.18 Units on a scale | Standard Deviation 2.47 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 70 minutes | 3.16 Units on a scale | Standard Deviation 2.49 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 80 minutes | 3.09 Units on a scale | Standard Deviation 2.55 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 100 minutes | 3.00 Units on a scale | Standard Deviation 2.62 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 110 minutes | 2.90 Units on a scale | Standard Deviation 2.6 |
| Benzocaine 10% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 120 minutes | 2.82 Units on a scale | Standard Deviation 2.61 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 30 minutes | 3.66 Units on a scale | Standard Deviation 2.38 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 110 minutes | 2.96 Units on a scale | Standard Deviation 2.59 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 80 minutes | 3.24 Units on a scale | Standard Deviation 2.6 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 25 minutes | 3.73 Units on a scale | Standard Deviation 2.27 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 20 minutes | 3.74 Units on a scale | Standard Deviation 2.23 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 90 minutes | 3.09 Units on a scale | Standard Deviation 2.61 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 15 minutes | 3.96 Units on a scale | Standard Deviation 2.07 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 5 minutes | 3.66 Units on a scale | Standard Deviation 1.87 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 100 minutes | 2.93 Units on a scale | Standard Deviation 2.58 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 50 minutes | 3.42 Units on a scale | Standard Deviation 2.45 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 10 minutes | 3.88 Units on a scale | Standard Deviation 1.97 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 60 minutes | 3.38 Units on a scale | Standard Deviation 2.57 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 40 minutes | 3.52 Units on a scale | Standard Deviation 2.43 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 120 minutes | 2.84 Units on a scale | Standard Deviation 2.56 |
| Benzocaine 20% | Pain Relief Combined With Pain Intensity Difference (PRID) Scores | 70 minutes | 3.33 Units on a scale | Standard Deviation 2.59 |
Comparison: 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.p-value: <0.00195% CI: [0.5, 1.35]ANOVA
Comparison: 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.p-value: 0.01195% CI: [0.13, 0.97]ANOVA
Comparison: 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.p-value: 0.03195% CI: [0.03, 0.72]ANOVA
Comparison: 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.p-value: <0.00195% CI: [0.33, 1.23]ANOVA
Comparison: 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.p-value: 0.03195% CI: [0.04, 0.94]ANOVA
Comparison: 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.p-value: 0.11995% CI: [-0.07, 0.66]ANOVA
Comparison: 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.p-value: 0.00295% CI: [0.28, 1.25]ANOVA
Comparison: 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.p-value: 0.06195% CI: [-0.02, 0.95]ANOVA
Comparison: 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.p-value: 0.13195% CI: [-0.09, 0.7]ANOVA
Comparison: 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.p-value: 0.04495% CI: [0.01, 1.03]ANOVA
Comparison: 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.p-value: 0.09995% CI: [-0.08, 0.93]ANOVA
Comparison: 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.p-value: 0.64795% CI: [-0.32, 0.51]ANOVA
Comparison: 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.p-value: 0.02395% CI: [0.08, 1.11]ANOVA
Comparison: 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.p-value: 0.07295% CI: [-0.04, 0.98]ANOVA
Comparison: 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.p-value: 0.55195% CI: [-0.29, 0.55]ANOVA
Comparison: 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.p-value: 0.04795% CI: [0.01, 1.08]ANOVA
Comparison: 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.p-value: 0.31695% CI: [-0.26, 0.81]ANOVA
Comparison: 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.p-value: 0.22495% CI: [-0.17, 0.71]ANOVA
Comparison: 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.p-value: 0.09995% CI: [-0.09, 1.01]ANOVA
Comparison: 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.p-value: 0.18695% CI: [-0.18, 0.92]ANOVA
Comparison: 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.p-value: 0.68495% CI: [-0.35, 0.54]ANOVA
Comparison: 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.p-value: 0.45295% CI: [-0.34, 0.76]ANOVA
Comparison: 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.p-value: 0.47995% CI: [-0.35, 0.75]ANOVA
Comparison: 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.p-value: 0.95595% CI: [-0.44, 0.46]ANOVA
Comparison: 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.p-value: 0.46595% CI: [-0.36, 0.79]ANOVA
Comparison: 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.p-value: 0.99295% CI: [-0.57, 0.58]ANOVA
Comparison: 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.p-value: 0.37695% CI: [-0.26, 0.68]ANOVA
Comparison: 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.p-value: 0.22995% CI: [-0.22, 0.93]ANOVA
Comparison: 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.p-value: 0.58195% CI: [-0.41, 0.74]ANOVA
Comparison: 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.p-value: 0.42295% CI: [-0.28, 0.66]ANOVA
Comparison: 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.p-value: 0.27195% CI: [-0.26, 0.91]ANOVA
Comparison: 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.p-value: 0.61295% CI: [-0.43, 0.73]ANOVA
Comparison: 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.p-value: 0.46595% CI: [-0.3, 0.65]ANOVA
Comparison: 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.p-value: 0.2995% CI: [-0.27, 0.91]ANOVA
Comparison: 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.p-value: 0.41295% CI: [-0.34, 0.83]ANOVA
Comparison: 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.p-value: 0.76995% CI: [-0.41, 0.55]ANOVA
Comparison: 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.p-value: 0.6195% CI: [-0.43, 0.74]ANOVA
Comparison: 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.p-value: 0.51195% CI: [-0.39, 0.78]ANOVA
Comparison: 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.p-value: 0.85995% CI: [-0.52, 0.43]ANOVA
Comparison: 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.p-value: 0.38695% CI: [-0.33, 0.84]ANOVA
Comparison: 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.p-value: 0.56395% CI: [-0.41, 0.76]ANOVA
Comparison: 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.p-value: 0.72195% CI: [-0.39, 0.56]ANOVA
Comparison: 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.p-value: 0.72595% CI: [-0.48, 0.69]ANOVA
Comparison: 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.p-value: 0.83995% CI: [-0.52, 0.64]ANOVA
Comparison: 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.p-value: 0.85595% CI: [-0.43, 0.52]ANOVA
Secondary
Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 60 | 3.1 Units on a scale | Standard Deviation 2.3 |
| Placebo | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 120 | 5.9 Units on a scale | Standard Deviation 4.8 |
| Benzocaine 10% | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 60 | 3.4 Units on a scale | Standard Deviation 2 |
| Benzocaine 10% | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 120 | 6.4 Units on a scale | Standard Deviation 4.2 |
| Benzocaine 20% | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 60 | 3.6 Units on a scale | Standard Deviation 2 |
| Benzocaine 20% | Sum of Pain Relief Combined With Pain Intensity Differences (SPRID) Scores | SPRID 120 | 6.7 Units on a scale | Standard Deviation 4.3 |
Comparison: 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.p-value: 0.03595% CI: [0.03, 0.95]ANOVA
Comparison: 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.p-value: 0.17395% CI: [-0.14, 0.78]ANOVA
Comparison: 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.p-value: 0.35895% CI: [-0.2, 0.55]ANOVA
Comparison: 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.p-value: 0.13595% CI: [-0.23, 1.72]ANOVA
Comparison: 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.p-value: 0.33295% CI: [-0.49, 1.46]ANOVA
Comparison: 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.p-value: 0.51795% CI: [-0.53, 1.06]ANOVA
Secondary
Time to Dropping Out Due to Lack of Efficacy or Rescue Medication
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Dropping Out Due to Lack of Efficacy or Rescue Medication | NA Minutes |
| Benzocaine 10% | Time to Dropping Out Due to Lack of Efficacy or Rescue Medication | NA Minutes |
| Benzocaine 20% | Time to Dropping Out Due to Lack of Efficacy or Rescue Medication | NA Minutes |
Secondary
Time to First Confirmed Perceptible Relief
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Confirmed Perceptible Relief | 2.0 Minutes |
| Benzocaine 10% | Time to First Confirmed Perceptible Relief | 1.4 Minutes |
| Benzocaine 20% | Time to First Confirmed Perceptible Relief | 1.1 Minutes |
Comparison: 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.p-value: <0.00195% CI: [1.55, 2.64]Regression, Cox
Comparison: 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.p-value: <0.00195% CI: [1.26, 2.12]Regression, Cox
Comparison: 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.p-value: 0.0395% CI: [1.02, 1.51]Regression, Cox
Secondary
Time to Meaningful Relief
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
Population: ITT population included all randomized participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Meaningful Relief | 8.5 Minutes |
| Benzocaine 10% | Time to Meaningful Relief | 4.4 Minutes |
| Benzocaine 20% | Time to Meaningful Relief | 3.2 Minutes |
Comparison: 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.p-value: <0.00195% CI: [1.57, 2.66]Regression, Cox
Comparison: 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.p-value: <0.00195% CI: [1.34, 2.25]Regression, Cox
Comparison: 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.p-value: 0.195% CI: [0.97, 1.43]Regression, Cox
Other Pre-specified
Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied
Amount of study medication applied was calculated by weighing medication tube prior and post-dosing.
Time frame: Baseline and 5 minutes
Population: Safety population included all participants who received at least 1 dose of study medication and had follow up data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied | 258.6 Milligram (mg) | Standard Deviation 163.4 |
| Benzocaine 10% | Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied | 226.8 Milligram (mg) | Standard Deviation 138.2 |
| Benzocaine 20% | Dosing Compliance Calculated by Evaluating Amount of Study Medication Applied | 233.1 Milligram (mg) | Standard Deviation 150.7 |
Other Pre-specified
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
Population: Safety population included all participants who received at least 1 dose of study medication and had follow up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication | 83.5 Percentage of participants |
| Benzocaine 10% | Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication | 89.3 Percentage of participants |
| Benzocaine 20% | Dosing Compliance Calculated by Evaluating Percentage of Participants Who Applied no More Than 400 mg of the Study Medication | 89.5 Percentage of participants |