A Study of Ibuprofen (IBU) 250mg/APAP 500mg In The Treatment Of Post-Surgical Dental Pain

Study Overview
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Brief Summary
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This study is being conducted to determine the overall analgesic efficacy and safety of a fixed-dose ibuprofen 250 mg / acetaminophen 500 mg formulation compared to placebo in subjects who are experiencing post operative pain following surgical extraction of 3 or more third molar teeth. A review of any reported adverse events will also be completed.

Official Title
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A Phase 3, Double-blind, Randomized Safety And Efficacy Study Comparing Multiple Administrations Of Ibu 250 Mg/Apap 500 Mg (Administered As Two Tablets Of Ibu/Apap 125 Mg/250 Mg) To Placebo In The Treatment Of Post Surgical Dental Pain In Adult Subjects

Conditions
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Pain

Intervention / Treatment
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* Drug: FDC IBU/APAP 250 mg/500 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females 18 years to 40 years of age (inclusive). Outpatients who have undergone surgical extraction of 3 or more third molars, of which at least 2 must be a partial or complete bony mandibular impaction. Subject must have at least moderate pain on the 4 point categorical scale, confirmed by at least 50 mm on the 100 mm VAS PSR scale within approximately 5 hours (ie, less than or equal to 5 hours, 15 minutes) after surgery is completed. In general good health and have no contraindications to the study or rescue medication. Exclusion Criteria Presence or history of any significant hepatic, renal, endocrine, cardiovascular, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorder determined by the Investigator to place the subject at increased risk, including the presence or history within 2 years of screening of the following medical conditions/disorders: Gastrointestinal ulcer or gastrointestinal bleeding; Paralytic ileus or other gastrointestinal obstructive disorders; Bleeding disorder. Hypersensitivity to ibuprofen, naproxen, aspirin, or any other NSAID; or to APAP, tramadol, other opioids, or to their combinations. Prior use of any type of analgesic or NSAID within five half lives of that drug or less before taking the first dose of investigational product, except for pre anesthetic medication and anesthesia for the procedure. .

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fixed Dose Combination(FDC) IBU/APAP 250 mg/500 mg<br>FDC IBU/APAP 250 mg/500 mg | Drug: FDC IBU/APAP 250 mg/500 mg<br>* FDC IBU/APAP 250 mg/500 mg<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 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 Intensity Difference Scores on 11-Point Numerical Scale From 0 to 24 Hours Post-dose (SPID11 [0-24]) | Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11 [0-24]: Time-weighted sum of Pain Intensity Difference (PID) scores over 24 hours. SPID11 score range was -120 (worst score) to 240 (best score) for SPID 0-24. PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 =no pain to 10 =worst possible pain) from the baseline pain intensity scores (score range: 5 =moderate pain to 10 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -5 (worst score) to 10 (best score). | 0 to 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted Sum of Pain Intensity Difference Score on 11-Point Numerical Scale (SPID11) From 0 to 8, 6 to 8, 0 to 16, 8 to 16 and 0 to 48 Hours Post-dose | Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11 for various time intervals: Time-weighted sum of PID scores over time intervals of 0-8 hours, 6-8 hours, 0-16 hours, 8-16 hours and 0-48 hours. SPID11 score range was -40 (worst score) to 80 (best score) for (SPID11 [0-8]), -15 (worst score) to 30 (best score) for (SPID11 [6-8]), -80 (worst score) to 160 (best score) for (SPID11 [0-16]), -45 (worst score) to 90 (best score) for (SPID11 [8-16]), -240 (worst score) to 480 (best score) for (SPID11 [0-48]). PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 =no pain to 10 =worst possible pain) from the baseline pain intensity scores (score range: 5 =moderate pain to 10 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -5 (worst score) to 10 (best score). | 0 to 8 hours, 6 to 8 hours, 0 to 16 hours, 8 to 16 hours and 0 to 48 hours post dose | 
| Duration of Relief After First Dose | Duration of relief (in minutes) was defined as the time interval from the administration of first dose of study drug up to the administration of a rescue medication or discontinuation of the participant from the study due to lack of efficacy or administration of second dose of study drug, whichever occurred first. If prior to taking rescue medication or secondary dose, a participant discontinued early from the study due to other reasons, the time was censored at time when the participant last performed a study evaluation prior to the discontinuation. | Up to 8 hours after first dose | 
| Time to Onset of Meaningful Pain Relief After First Dose | Using the double stopwatch method, participants started two stopwatches soon after dosing. Participants evaluated time to meaningful relief after first dose by stopping the second stopwatch labelled as meaningful relief at the moment they first began to experience meaningful relief after the administration of first dose and prior to the administration of second dose of study drug. The stopwatch was active for up to 8 hours after dosing or until stopped by the participant, or until second dose or a rescue medication whichever is administered first. | Up to 8 hours after first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ibuprofen, acetaminophen, pain, molar extraction