Study of Acetaminophen (ACE) in Post-operative Dental Pain

Study Overview
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Brief Summary
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This is a dental pain study evaluating the efficacy and safety of a single dose of test acetaminophen (ACE) (1000 mg) compared to commercial acetaminophen (1000 mg), ibuprofen (IBU) (400 mg), and placebo over a 6 hour period. 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, Safety, and Pharmacokinetics Proof of Concept Study of a Test Acetaminophen 500 mg Tablet in Postoperative Dental Pain

Conditions
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Dental Pain

Intervention / Treatment
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* Drug: Acetaminophen (ACE) (1000 mg)
* Drug: Commercial ACE (1000 mg)
* Drug: Commercial Ibuprofen (IBU) (400 mg)
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are 17 to 50 years of age Weigh 100 lbs or greater and body mass index (BMI) 18 to 30 (inclusive) Dental extraction of three or four third-molars. Experience moderate to severe pain after extraction of third molars Exclusion Criteria: Currently pregnant (or planning to be pregnant) or nursing a baby Known allergy to acetaminophen (ACE) or non-steroidal anti-inflammatory drugs (NSAIDs) 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

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Acetaminophen (ACE) (1000 mg) and placebo<br> | Drug: Acetaminophen (ACE) (1000 mg)<br>* 2 Test ACE 500 mg tablets taken orally one time<br>Drug: Placebo<br>* 2 placebo caplets for acetaminophen taken orally one time<br>Drug: Placebo<br>* 2 placebo soft-gels for ibuprofen taken orally one time<br>|
| Active Comparator: Commerical ACE (1000 mg) and placebo<br> | Drug: Commercial ACE (1000 mg)<br>* 2 ACE 500 mg caplets taken orally one time<br>Drug: Placebo<br>* 2 placebo soft-gels for ibuprofen taken orally one time<br>Drug: Placebo<br>* 2 placebo tablets for Test acetaminophen taken orally one time<br>|
| Active Comparator: Commerical Ibuprofen (IBU) (400 mg) and placebo<br> | Drug: Commercial Ibuprofen (IBU) (400 mg)<br>* 2 IBU 200 mg soft-gels taken orally one time<br>Drug: Placebo<br>* 2 placebo caplets for acetaminophen taken orally one time<br>Drug: Placebo<br>* 2 placebo tablets for Test acetaminophen taken orally one time<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 2 placebo caplets for acetaminophen taken orally one time<br>Drug: Placebo<br>* 2 placebo soft-gels for ibuprofen taken orally one time<br>Drug: Placebo<br>* 2 placebo tablets for Test acetaminophen taken orally one time<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time weighted sum of pain intensity difference from 0-6 hours (SPID 0-6) | Time weighted sum of pain intensity difference scores from baseline over 6 hours. Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 6 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time weighted sum of pain intensity difference from 0-4 hours (SPID 0-4) | Time weighted sum of pain intensity difference scores from baseline over 4 hours. Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 4 Hours | 
| Time to meaningful pain relief | Minutes until meaningful pain relief are achieved. Stopwatch is started after the subject takes the study medication. The subjects are instructed to stop the stopwatch when the relief from the starting pain is meaningful to them. | Within 6 Hours | 
| Time to first perceptible pain relief | Minutes until first perceptible pain relief is achieved. Stopwatch is started after the subject takes the study medication. The subject is instructed to stop the stopwatch when they first begin to feel any pain relief. | Within 6 Hours | 
| Time to confirmed first perceptible relief | Minutes until confirmed first perceptible pain relief are achieved. Stopwatch is started after the subject takes the study medication. The subject is instructed to stop the stopwatch when they first begin to feel any pain relief. The first perceptible pain relief is confirmed if the subject also stopped the second stopwatch indicating meaningful pain relief. | Within 6 Hours | 
| Time weighted sum of pain relief from 0-4 (TOTPAR 0-4) | Time weighted sum of pain relief scores over four hours. Pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 4 hours | 
| Time weighted sum of pain relief from 0-6 (TOTPAR 0-6) | Time weighted sum of pain relief scores over six hours. Pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 6 hours | 
| Duration of relief after dosing (time to rescue analgesic) | Minutes until rescue medication is given | 6 Hours | 
| Proportion of subjects taking a rescue analgesic by 6 hours | Percentage of subjects using rescue medication through six hours | 6 Hours | 
| Subject Global Evaluation assessed at hour 6 or at time of rescue | Patient assessment of the pain medication - number of subjects rating the medication they received as a pain reliever on a score of 0-4, where 0=poor, 1=fair, 2=good, 3=very good, 4=excellent | 6 hours | 
| Pain relief (PAR) scores at 0.25 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 0.25 Hours | 
| Pain relief (PAR) scores at 0.5 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 0.5 Hours | 
| Pain relief (PAR) scores at 0.75 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 0.75 Hours | 
| Pain relief (PAR) scores at 1 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 1 Hours | 
| Pain relief (PAR) scores at 1.25 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 1.25 Hours | 
| Pain relief (PAR) scores at 1.5 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 1.5 Hours | 
| Pain relief (PAR) scores at 2 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 2 hoursH | 
| Pain relief (PAR) scores at 3 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 3 Hours | 
| Pain relief (PAR) scores at 4 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 4 Hours | 
| Pain relief (PAR) scores at 5 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 5 Hours | 
| Pain relief (PAR) scores at 6 Hours | Pain relief scores at each assessment time point - pain relief was evaluated using a 0-10 pain relief numerical rating scale (PR-NRS) where 0 = no relief and 10 = complete relief | 6 Hours | 
| Pain intensity difference (PID) at 0.25 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 0.25 Hours | 
| Pain intensity difference (PID) at 0.5 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 0.5 Hours | 
| Pain intensity difference (PID) at 0.75 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 0.75 Hours | 
| Pain intensity difference (PID) at 1 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 1 Hours | 
| Pain intensity difference (PID) at 1.25 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 1.25 Hours | 
| Pain intensity difference (PID) at 1.5 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 1.5 Hours | 
| Pain intensity difference (PID) at 2 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 2 Hours | 
| Pain intensity difference (PID) at 3 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 3 Hours | 
| Pain intensity difference (PID) at 4 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 4 Hours | 
| Pain intensity difference (PID) at 5 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 5 Hours | 
| Pain intensity difference (PID) at 6 Hours | Pain intensity difference (PID) from baseline at each assessment time point - Pain intensity was evaluated using a 0-10 pain intensity numerical rating scale (PI-NRS) where 0 = no pain and 10 = very severe pain | 6 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Molar,third; Teeth,wisdom; Pain, Postoperative; Dental Surgery; Third molar extraction