Evaluation of the Efficacy of Novel Ibuprofen Acetaminophen Combination Formulations in the Treatment of Post-surgical Dental Pain

Study Overview
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Brief Summary
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This study will determine the overall analgesic efficacy of three different fixed dose ibuprofen plus acetaminophen formulations compared to ibuprofen alone and to placebo.

Official Title
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EVALUATION OF THE EFFICACY OF NOVEL IBUPROFEN ACETAMINOPHEN COMBINATION FORMULATIONS IN THE TREATMENT OF POST-SURGICAL DENTAL PAIN

Conditions
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Pain

Intervention / Treatment
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* Drug: Ibuprofen/acetaminophen
* Drug: Ibuprofen/acetaminophen
* Drug: Ibuprofen/acetaminophen
* Drug: Ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 16 to 40 years of age Moderate to severe post-operative pain following surgical extraction of three or more third molar teeth Exclusion Criteria: Presence of history of significant hepatic, renal, endocrine, cardiovascular, neurological, psychiatric, gastrointestinal, pulmonary, hematologic or metabolic disorder Pregnant or breastfeeding females

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen/acetaminophen (lower dose)<br> | Drug: Ibuprofen/acetaminophen<br>* Two caplets of ibuprofen 100 mg plus acetaminophen 250 mg<br>|
| Experimental: Ibuprofen/acetaminophen (middle dose)<br> | Drug: Ibuprofen/acetaminophen<br>* Two caplets of ibuprofen 125 mg plus acetaminophen 250 mg<br>|
| Experimental: Ibuprofen/acetaminophen (high dose)<br> | Drug: Ibuprofen/acetaminophen<br>* Two caplets of ibuprofen 150 mg plus acetaminophen 250 mg<br>|
| Active Comparator: Ibuprofen<br> | Drug: Ibuprofen<br>* Two caplets of ibuprofen 200 mg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Two caplets 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 Scores From 0 to 8 Hours (SPRID 0-8) | SPRID4:Time-weighted sum of pain relief rating (PRR) and pain intensity difference (PID) based on 4 point categorical severity rating scale (PRID) over 8 hours.SPRID 0-8 score range:-8 (worst score) to 56 (best score).PRID: sum of PRR and PID at each time point.PRID score range:-1= worst score to 7= best score.PID4 was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [none] to 3 [severe]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 = severe pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -1 (worst score) to 3 (best score).PRR assessed on 5-point categorical scale with range:0 =no relief to 4 =complete relief. | From 0 hour up to 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Onset of Meaningful Pain Relief | Participants evaluated time to meaningful relief by stopping a second stopwatch labelled as meaningful relief at the moment they first began to experience meaningful relief. Stopwatch was active up to 12 hours after dosing or until stopped by participant, or participant became treatment failure prior to depressing the second stopwatch. Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy. | From 0 hour up to 12 hours post-dose | 
| Time to Confirmed First Perceptible Relief | Participants evaluated the time to first perceptible relief (confirmed by meaningful relief) by stopping the first stopwatch labelled 'first perceptible relief' at the moment they first began to experience any pain relief, if the participant also achieved meaningful relief by the end of the study. Stopwatch was active up to 12 hours after dosing or until stopped by the participant, or until the participant dropped out due to treatment failure (defined as participant taking rescue medication, or discontinuing due to lack of efficacy) prior to depressing the first stopwatch or until the time of withdrawal (discontinuation). | From 0 hour up to 12 hours post-dose | 
| Pain Relief Rating Score (PRR) | Participants answered a question: how much relief do you have from your starting pain? on a 5-point categorical pain relief rating scale. Scale ranges from 0= no relief to 4= complete relief. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Pain Intensity Difference on 4-Point Categorical Scale (PID4) | PID4: baseline pain severity score minus pain severity score at a given time point. Pain intensity was assessed on a 4-point categorical pain severity rating scale. PID4 was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [no pain] to 3 [worst possible pain]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID4: -1 (worst score) to 3 (best score). | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Pain Intensity Difference on 11-Point Numerical Scale (PID11) | PID11: baseline pain severity score minus pain severity score at a given time point. Pain intensity was assessed on an 11-point numerical pain severity rating scale. PID11 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 PID11: -5 (worst score) to 10 (best score). | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Sum of Pain Relief Rating and Pain Intensity Difference on 4-Point Categorical Scale (PRID4) | PRID4: sum of PID and PRR at each post-dose time points up to 12 hours. Score range for PRID: -1(worst score) to 7(best score). PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [no pain] to 3 [worst possible pain]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID4: -1 (worst score) to 3 (best score). PRR was assessed on a 5-point categorical pain relief rating scale which ranges from 0 =no relief to 4 =complete relief. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Time-weighted Sum of Pain Intensity Difference on 4-Point Categorical Scale (SPID4) Over 2, 6, 8 and 12 Hours Post-Dose | Pain intensity was assessed on a 4-point categorical pain severity rating scale. SPID4: Time-weighted sum of PID over post-dose time points. SPID4 score range was -2 (worst score) to 6 (best score) for SPID 0-2, -6 (worst score) to 18 (best score) for SPID 0-6, -8 (worst score) to 24 (best score) for SPID 0-8, -12 (worst score) to 36 (best score) for SPID 0-12. PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [none] to 3 [severe]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 = severe pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -1 (worst score) to 3 (best score). | 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12 hours post-dose | 
| Time-weighted Sum of Pain Intensity Difference on 11-Point Numerical Scale (SPID11) Over 2, 6, 8 and 12 Hours Post-Dose | Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11: Time-weighted sum of PID scores over 12 hours. SPID11 score range was -10 (worst score) to 20 (best score) for SPID 0-2, -30 (worst score) to 60 (best score) for SPID 0-6, -40 (worst score) to 80 (best score) for SPID 0-8, -60 (worst score) to 120 (best score) for SPID 0-12. 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 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12 hours post-dose | 
| Time-weighted Sum of Pain Relief Rating (TOTPAR) Over 2, 6, 8, 12 Hours Post-Dose | TOTPAR: time-weighted sum of PRR scores over 2, 6, 8 and 12 hours. TOTPAR score range was 0 (worst score) to 8 (best score) for TOTPAR 0-2, 0 (worst score) to 24 (best score) for TOTPAR 0-6, 0 (worst score) to 32 (best score) for TOTPAR 0-8, 0 (worst score) to 48 (best score) for TOTPAR 0-12. PRR was assessed on a 5-point categorical pain relief rating scale where 0= No relief to 4= Complete relief. | 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12 hours post-dose | 
| Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference on 4-Point Categorical Scale (SPRID4) Over 2, 6 and 12 Hours Post Dose | SPRID4: Time-weighted sum of PRR and PID based on 4 point categorical pain severity rating scale (PRID) with score range: -2(worst score) to 14 (best score) for SPRID 0-2, -6 (worst score) to 42 (best score) for SPRID 0-6 and -12 (worst score) to 84 (best score) for SPRID 0-12. PRID: sum of PID and PRR at post-dose time point with score range: -1 (worst score) to 7 (best score). PID calculated by subtracting pain intensity score at post-dose time points (score range: 0 [none] to 3 [severe]) from baseline pain intensity scores (score range: 2 =moderate pain to 3 = severe pain; as participants with baseline score of at least moderate were included). PID total possible score range: -1 (worst score) to 3(best score). PRR assessed on 5-point categorical scale with range: 0 =no relief to 4 =complete relief. | 0 to 2 hours, 0 to 6 hours, 0 to 12 hours post-dose | 
| Cumulative Percentage of Participants With Meaningful Relief | Percentage of participants with meaningful relief was reported. Participants evaluated 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 12 hours after dosing or until stopped by participant, or participant became treatment failure prior to depressing the second stopwatch. Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Cumulative Percentage of Participants With Confirmed First Perceptible Relief | Percentage of participants with confirmed first perceptible relief was reported. Participants evaluated the time to first perceptible relief (confirmed by meaningful relief) by stopping the first stopwatch labelled 'first perceptible relief' at the moment they first began to experience any pain relief, if the participant also achieved meaningful relief by the end of the study. Stopwatch was active up to 12 hours after dosing or until stopped by the participant, or until the participant dropped out due to treatment failure prior to depressing the first stopwatch or until the time of withdrawal (discontinuation). Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Time to Treatment Failure | Time to treatment failure was defined as the time interval from the study drug administration up to the first documentation of treatment failure. Treatment failure was defined as taking the rescue medication or discontinuation of the participants from the study due to lack of efficacy, whichever came first. Participants were censored at 12 hours or at their final assessment time, whichever came first. | From 0 hour up to 12 hours post-dose | 
| Cumulative Percentage of Participants With Treatment Failure | Treatment failure was defined as taking the rescue medication or discontinuation of the participants from the study due to lack of efficacy, whichever came first. Participants were censored at 12 hours or at their final assessment time, whichever came first. Percentage of participants who had treatment failure were reported. | 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose | 
| Participant Global Evaluation of Study Medication | Participant global evaluation of study medication was performed at the 12-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. | 12 hour | 

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