Randomized, Double-Blind, Single-Dose, Efficacy and Safety Study of Test Acetaminophen Tablet in Postoperative Dental Pain

Study Overview
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Brief Summary
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To evaluate analgesic onset, efficacy, and safety of 1000 mg acetaminophen administered as two Test Acetaminophen 500 mg tablets (Test ACM) compared with 1000 mg acetaminophen administered as two commercial acetaminophen 500 mg caplets (ACM) and 400 mg ibuprofen administered as two commercial ibuprofen 200 mg liquid-filled capsules (IBU) in the dental pain model following third-molar extractions.

Detailed Description
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This is a single-dose, randomized, double-blind, placebo- and active- controlled, parallel-group study to evaluate the analgesic onset, efficacy, and safety profile of Test ACM 1000 mg compared with two commercial products over a four-hour period after third-molar extractions. Subjects will undergo dental extraction of three or four third molars.

Official Title
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A Randomized, Double-Blind, Placebo- and Active- Controlled, Single-Dose, Efficacy and Safety Study of a Test Acetaminophen 500 mg Tablet in Postoperative Dental Pain

Conditions
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Post-operative Dental Pain

Intervention / Treatment
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* Drug: Test acetaminophen
* Drug: Commercial acetaminophen
* Drug: Commercial ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 17 to 50 years old Weigh 100 lbs. or greater and have a body mass index (BMI) of 18 to 30 (inclusive) Dental extraction of three or four third molars Meets post-surgical pain criteria Females of childbearing age must be willing to use acceptable method of birth control Exclusion Criteria: Currently pregnant or planning to be pregnant or nursing a baby Known allergy to acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, as well as hydrocodone or other opioids Inability to swallow whole large tablets or capsules Have other conditions that the investigator feels may impact subject's safety and/or the integrity of the study Use of pain medications 5 or more times per week Have a history of chronic tranquilizer use, heavy drinking, or substance abuse in the last 5 years History of endoscopically documented peptic ulcer disease or bleeding disorder in the last 2 years Have a positive urine drug screen

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 50 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
Interventional Model Description: Post-operative dental pain following third molar extraction.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test acetaminophen<br>Test acetaminophen 1000 mg dose | Drug: Test acetaminophen<br>* single dose of 2 Test acetaminophen 500 mg tablets<br>* Other names: Test ACM;|
| Active Comparator: Commercial acetaminophen<br>Commercial acetaminophen 1000 mg dose | Drug: Commercial acetaminophen<br>* single dose of 2 acetaminophen 500 mg caplets<br>* Other names: Commercial ACM;|
| Active Comparator: Commercial ibuprofen<br>Commercial ibuprofen, 400 mg dose | Drug: Commercial ibuprofen<br>* Single dose of 2 ibuprofen 200 mg Liquid-filled Capsules<br>* Other names: Commercial IBU;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 2 placebo caplets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Confirmed Perceptible Pain Relief | Minutes until confirmed perceptible pain relief is achieved. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. | within 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Meaningful Pain Relief | Minutes until meaningful pain relief is achieved. Stopwatch is started after the participant takes the study medication. The participants are instructed to stop the stopwatch when the relief from the starting pain is meaningful to them. | Within 4 hours | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 30 Minutes | Percentage of participants with confirmed perceptible relief by 30 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 30 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 29 Minutes | Percentage of participants with confirmed perceptible relief by 29 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 29 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 28 Minutes | Percentage of participants with confirmed perceptible relief by 28 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 28 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 27 Minutes | Percentage of participants with confirmed perceptible relief by 27 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 27 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 26 Minutes | Percentage of participants with confirmed perceptible relief by 26 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 26 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 25 Minutes | Percentage of participants with confirmed perceptible relief by 25 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 25 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 24 Minutes | Percentage of participants with confirmed perceptible relief by 24 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 24 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 23 Minutes | Percentage of participants with confirmed perceptible relief by 23 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 23 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 22 Minutes | Percentage of participants with confirmed perceptible relief by 22 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 22 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 21 Minutes | Percentage of participants with confirmed perceptible relief by 21 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 21 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 20 Minutes | Percentage of participants with confirmed perceptible relief by 20 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 20 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 19 Minutes | Percentage of participants with confirmed perceptible relief by 19 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 19 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 18 Minutes | Percentage of participants with confirmed perceptible relief by 18 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 18 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 17 Minutes | Percentage of participants with confirmed perceptible relief by 17 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 17 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 16 Minutes | Percentage of participants with confirmed perceptible relief by 16 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 16 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 15 Minutes | Percentage of participants with confirmed perceptible relief by 15 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 15 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 14 Minutes | Percentage of participants with confirmed perceptible relief by 14 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 14 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 13 Minutes | Percentage of participants with confirmed perceptible relief by 13 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 13 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 12 Minutes | Percentage of participants with confirmed perceptible relief by 12 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 12 minutes | 
| Percentage of Participants With Confirmed Perceptible Relief From 30 Minutes to Successively Earlier Minutes in One-minute Increments - 11 Minutes | Percentage of participants with confirmed perceptible relief by 11 minutes. Stopwatch is started after the participant takes the study medication. The participant is instructed to stop the stopwatch when they first begin to feel any pain relief. The perceptible pain relief is confirmed if the participant also stopped the second stopwatch indicating meaningful pain relief. Test acetaminophen 1000 mg and placebo were compared on the percentage of subjects with confirmed perceptible relief starting at 30 minutes and testing successively earlier minutes (29, 28, etc) until the difference was no longer statistically significant. The earliest significant time was identified. | by 11 minutes |