Multiple Dose Dental Pain Study Of Ibuprofen Extended Release

Study Overview
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Brief Summary
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The study hypothesis is that single and multiple doses of ibuprofen 600 mg ER caplets provide analgesic efficacy superior to placebo over 12-hour dosing intervals.

Official Title
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A Multiple Dose Dental Pain Study Of An Ibuprofen 600 Mg Extended Release Caplet

Conditions
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Pain

Intervention / Treatment
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* Drug: Ibuprofen 600 mg ER
* 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 Subjects who undergo surgical removal of at least two third molars One of which must be a partial or full bony mandibular impaction Subjects must have at least moderate baseline pain (a score of 2 on the categorical pain severity rating scale) confirmed by a score of at least 50 mm on the 100-mm visual analog scale-pain severity rating scale (VAS-PSR) Exclusion Criteria: Acute localized dental infection at the time of surgery that could confound the post-surgical evaluation Presence or history of any significant organ disease Use of prescription or OTC first generation antihistamines Females who are pregnant, lactating or of childbearing potential and not using a medically approved method to prevent pregnancy

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen 600 mg extended release<br> | Drug: Ibuprofen 600 mg ER<br>* One 600 mg caplet dosed at 0, 12, 24 and 36 hours<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One placebo caplet dosed at times 0, 12, 24 and 36 hours<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 and Pain Intensity Difference Scores From 0 to 12 Hours After the First Dose (SPRID 0-12) | SPRID is time-weighted sum of pain relief (PR) plus pain intensity (PI) difference (PID) (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0 equals [=] none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for PI: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement in pain intensity. SPRID 0-12 score ranged from -12 to 84; higher score indicated better efficacy. | Baseline to 12 hours | 
| Sum of Pain Relief and Pain Intensity Difference Scores From 8-12 Hours After the First Dose | SPRID is time-weighted sum of PR plus PID (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPRID 8-12 score ranged from -4 to 28; higher score indicated better efficacy. | 8 to 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID is a derived endpoint from PID scores. For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPID scores ranged as follows: 0 to 12 hour (-11.5 to 35.5), 8 to 12 hour (-6.0 to 18.0), 12 to 24 hour (-14.0 to 42.0), 20 to 24 hour (-8.0 to 24.0), 0 to 24 hour (-23.5 to 71.5), 24 to 36 hour (-16.0 to 48.0), 32 to 36 hour (-8.0 to 24.0), 36 to 48 hour (-16.0 to 48.0), 44 to 48 hour (-8.0 to 24.0), 24 to 48 hour (-28.0 to 84.0); higher positive values indicated improvement (decrease) in pain intensity. | 0 to 12 hours, 8 to 12 hours, 12 to 24 hours, 20 to 24 hours, 0 to 24 hours, 24 to 36 hours, 32 to 36 hours, 36 to 48 hours, 44 to 48 hours, 24 to 48 hours | 
| Time to First Dose of Rescue Medication After First Dose of Study Drug | During the first 12 hours of the study, participants not experiencing adequate relief after the 1-hour time point were allowed to take a single tablet (dose) of acetaminophen/hydrocodone hydrochloride (HCl) 500 mg/5 mg as a rescue medication (the only rescue medication allowed). The time at which rescue medication was taken was recorded. | Baseline to 12 hours | 
| Percentage of Participants Taking Rescue Medication | Participants not experiencing adequate relief after the 1-hour time point during each dosing interval were allowed to take a single tablet (dose) of acetaminophen/hydrocodone HCl 500 mg/5 mg as a rescue medication (the only rescue medication allowed) during each interval. | Baseline to 48 hours | 
| Pain Relief (PR) Scores | A 5-point categorical pain relief rating scale was used to rate pain relief in response to the question: How much relief do you have from your starting pain? Responses were scored as follows: 0=none, 1=a little, 2=some, 3=a lot, 4=complete. Higher score indicated more pain relief. | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours | 
| Pain Intensity Difference (PID) Scores | For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale. Responses were scored as follows: 0=none, 1=mild, 2=moderate, 3=severe. PID score=baseline pain intensity score minus score at each time point. PID scores ranged from -1 to 3. Higher positive PID scores indicated greater improvement (decrease in pain intensity). | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 hours | 
| Pain Relief Combined With Pain Intensity (PRID) Scores | PRID score=PR plus PID. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; PID score ranged from -1 to 3; higher positive PID value=improvement. PRID scores ranged from -1 to 7. Higher PRID scores indicated better pain relief and decrease in pain intensity. | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours | 
| Time-weighted Sum of Pain Relief Scores (TOTPAR) | TOTPAR is a derived endpoint from PR scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). TOTPAR 0-12 scores ranged from 0 (worst) to 48 (best). TOTPAR 8-12 scores ranged from 0 (worst) to 16 (best). | 0-12 hours, 8-12 hours | 
| Number of Doses of Rescue Medication Used |  | 0-12, 12-24, 24-36, 36-48, 0-48 hours | 
| Time to Confirmed First Perceptible Relief | The elapsed time from dosing until the participant indicated first perceptible pain relief by pressing the first stopwatch, provided the participant also indicated achieving meaningful relief by pressing the second stopwatch. Perceptible relief defined as when participant first began to feel any pain-relieving effect whatsoever of the drug. Did not necessarily mean the participant felt completely better, but when the participant first felt any difference in the pain he/she is currently feeling. | Baseline to 12 hours | 
| Time to Meaningful Relief | Participants evaluated the time to meaningful relief by depressing a second stopwatch at the moment they first began to experience meaningful relief, defined as relief from the pain that was considered meaningful to the participant. | Baseline to 12 hours | 
| Participant Global Evaluation Score | Participants responded, on a 6-point categorical scale, to the following question: How would you rate this medication as a pain-reliever? Responses on this categorical scale ranged as follows: 0=very poor, 1=poor, 2=fair, 3=good, 4=very good, 5=excellent. | 24 and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dental pain, multiple dose, ibuprofen, third molar extraction