Benzocaine Gel Toothache Dose-Response Study

Study Overview
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Brief Summary
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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.

Official Title
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Benzocaine Gel Toothache Dose-Response Study

Conditions
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Toothache

Intervention / Treatment
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* Drug: Placebo gel
* Drug: benzocaine
* Drug: benzocaine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo control | Drug: Placebo gel<br>* single dose (less than 1g) of a matching placebo gel<br>|
| Active Comparator: 2<br>10% benzocaine gel formulation | Drug: benzocaine<br>* single dose (less than 1g) of 10% benzocaine gel formulation<br>|
| Active Comparator: 3<br>20% benzocaine gel formulation | Drug: benzocaine<br>* single dose (less than 1g) of 20% benzocaine gel formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, 5, 10, 15 and 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 to 120 minutes | 
| 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. | 0 to 120 minutes | 
| 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. | 0 to 120 minutes | 
| 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). | 60 minutes and 120 minutes | 
| 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. | 0 to 120 minutes | 
| 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). | 5 to 120 minutes | 
| 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). | 120 minutes |