Study Evaluating A Novel Ibuprofen Formulation In The Treatment Of Dental Pain

Study Overview
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Brief Summary
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This study will compare the pain relieving effect of a single-dose of a novel ibuprofen formulation to placebo and two formulations of standard ibuprofen in the treatment of post-surgical dental pain following wisdom tooth (third molar) removal.

Official Title
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Evaluation Of The Efficacy Of A Novel Ibuprofen Formulation In The Treatment Of Post-Surgical Dental Pain: Study I

Conditions
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Pain

Intervention / Treatment
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* Drug: Novel Ibuprofen
* Drug: Standard Ibuprofen
* Drug: Standard Ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal, healthy males and females 16 to 40 years of age Outpatients who have moderate to severe post-operative pain (confirmed by a Visual Analog Scale-Pain Severity Rating [VAS-PSR] score of at least 50 mm on a 100 mm VAS-PSR) following surgical extraction of two or more third molars, at least one of which must be a partial or complete bony mandibular impaction Use of only the following pre-operative medication(s)/anesthetic(s): topical benzocaine, a short acting parenteral (local) anesthetic (mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide Exclusion Criteria: Pregnancy or breast-feeding Alcohol or substance abuse Any serious medical or psychiatric disorder History of stomach ulcers, stomach bleed, or other bleeding disorders Use of a prescription or over-the-counter drug with which administration of ibuprofen or any other non-steroidal anti-inflammatory drug, acetaminophen, or hydrocodone is contraindicated (including: opioids, antipsychotics, antianxiety agents, or other central nervous system depressants[including alcohol])

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 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: Treatment A<br> | Drug: Novel Ibuprofen<br>* Single-dose of novel ibuprofen (equal to 400 mg ibuprofen)<br>|
| Active Comparator: Treatment B<br> | Drug: Standard Ibuprofen<br>* Single-dose of standard ibuprofen (400mg)<br>|
| Active Comparator: Treatment C<br> | Drug: Standard Ibuprofen<br>* Single-dose of standard ibuprofen (400mg)<br>|
| Placebo Comparator: Treatment D<br> | Drug: Placebo<br>* Single-dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-8 Hours (SPRID 0-8) | SPRID: time-weighted sum of pain relief rating combined with pain intensity difference (PRID) over 8 hours. SPRID 0-8 score range: -8 (worst) to 56 (best). PRID: sum of Pain intensity differences (PID) and pain relief rating (PRR) at each time point. PRID score range: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (pain severity score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). PID score range: -1(worst) to 3 (best). PRR: assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief). | 0 to 8 hours | 
| Time to Onset of 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 8 hours after dosing or until stopped by the participant, or rescue medication was administered. | 0 to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Confirmed First 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 8 hours after dosing or until stopped by the participant, or rescue medication was administered. The first perceptible relief was considered confirmed if the participant also stopped the second stopwatch indicating meaningful relief. | 0 to 8 hours | 
| Pain Relief Rating (PRR) | PRR was evaluated at different time points during the study up to 8 hours after taking the study medication, and immediately before rescue medication was taken (if necessary). PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Pain Intensity Difference (PID) | PID was derived by subtracting the pain severity score at a given post-dosing time point (pain severity score range 0 [none] to 3 [severe]) from the baseline score (Baseline pain severity score range 2 [moderate] to 3 [severe]). Total possible score range for PID: -1 (worst) to 3 (best). | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Sum of Pain Relief Rating and Pain Intensity Difference (PRID) | PRID was sum of PID and PRR at each post-dosing time point. The overall possible score range, for PRID was -1 (worst) to 7 (best). PID was derived by subtracting the pain severity score at a given post-dosing time point (pain severity score range 0 [none] to 3 [severe]) from the baseline score (Baseline pain severity score range 2 [moderate] to 3 [severe]). Total possible score range for PID: -1 (worst) to 3 (best). PRR was assessed on 5-point categorical pain relief rating scale (0=No relief to 4=Complete relief). | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Time-weighted Sum of Pain Intensity Difference (SPID) | SPID: time-weighted sum of PID over 2, 3, 6 and 8 hours. SPID scores range was -2 (worst) to 6 (best) for SPID 0-2, -3 (worst) to 9 (best) for SPID 0-3, -6 (worst) to 18 (best) for SPID 0-6, -8 (worst) to 24 (best) for SPID 0-8. PID: baseline pain severity score minus pain severity score at a given time point (pain severity score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). Total score range for PID: -1(worst) to 3 (best). | 0-2, 0-3, 0-6, 0-8 hours | 
| Time-weighted Sum of Pain Relief Rating (TOTPAR) | TOTPAR: time-weighted sum of PRR scores over 2, 3, 6 and 8 hours. TOTPAR score range was 0 (worst) to 8 (best) for TOTPAR 0-2, 0 (worst) to 12 (best) for TOTPAR 0-3, 0 (worst) to 24 (best) for TOTPAR 0-6, 0 (worst) to 32 (best) for TOTPAR 0-8. PRR was evaluated at different time points during the study up to 8 hours, and immediately after taking rescue medication (if necessary). PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief. | 0-2, 0-3, 0-6, 0-8 hours | 
| Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID) | SPRID: time-weighted sum of PRID over 2, 3, 6 and 8 hours. SPRID score range:-2 (worst) to 14(best) for SPRID 0-2, -3(worst) to 21(best) for SPRID 0-3, -6(worst) to 42(best) for SPRID 0-6, -8(worst) to 56(best) for SPRID 0-8. PRID:sum of PID and PRR at each time point. Total score range for PRID: -1=worst to 7=best. PID:baseline pain severity score minus pain severity score at given time(score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). Total score range for PID: -1(worst) to 3(best), PRR: scored on 5-point pain relief rating scale(0=No relief to 4=Complete relief). | 0-2, 0-3, 0-6, 0-8 hours | 
| Cumulative Percentage of Participants With Meaningful Relief | Percentage of participants with meaningful relief evaluated by stopping the stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Cumulative Percentage of Participants With Confirmed First Perceptible Relief | Percentage of participants with first perceptible relief was evaluated by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered. The first perceptible relief was considered confirmed if the participant also stopped the second stopwatch indicating meaningful relief. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Time to Treatment Failure | Median time of dropping out of the participants from the study due to lack of efficacy or rescue medication, whichever came first. | 0 to 8 hours | 
| Cumulative Percentage of Participants With Treatment Failure | Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Cumulative Percentage of Participants With Complete Relief | Complete relief was defined as a PRR of 4. PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours | 
| Participant Global Evaluation of Study Medication | Participant global evaluation of study medication was performed at the 8-hour time point or immediately before taking the rescue medication. It was scored on a 6-point categorical scale where 0 = Very poor, 1 = Poor, 2 = Fair, 3 = Good, 4 = Very Good, and 5 = Excellent. | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain following third molar extraction