A Dental Pain Study Comparing The Analgesic Efficacy Of Ibuprofen/Caffeine

Study Overview
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Brief Summary
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An efficacy study assessing analgesic effect of ibuprofen/caffeine in post-surgical dental pain.

Detailed Description
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The purpose of this study is to assess the analgesic efficacy of a fixed dose combination of ibuprofen/caffeine compared to ibuprofen alone and also to placebo.

Official Title
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A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY COMPARING THE ANALGESIC EFFICACY AND SAFETY OF A SINGLE ORAL DOSE OF A NOVEL FIXED-DOSE COMBINATION OF IBUPROFEN 400 MG WITH CAFFEINE 100 MG TO IBUPROFEN 400 MG AND TO PLACEBO IN THE TREATMENT OF POST-SURGICAL DENTAL PAIN IN OTHERWISE HEALTHY SUBJECTS

Conditions
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Pain

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 16 years to 40 years of age (inclusive). Subjects who have undergone outpatient surgical extraction of 3 or more third molars, of which at least 2 must be a partial or complete bony mandibular impaction within 30 days of Screening and have met baseline pain criteria as described in this protocol Examined by the attending dentist or physician and medically cleared to participate in the study. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) 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: Bleeding disorder; Gastrointestinal ulcer or gastrointestinal bleeding; Paralytic ileus or other gastrointestinal obstructive disorders. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception Hypersensitivity to ibuprofen, naproxen, aspirin, or any other NSAID, caffeine, or other component of the product.

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/Caffeine<br>Ibuprofen 400 mg/ Caffeine 100 mg fixed-dose combination | Drug: Ibuprofen/Caffeine<br>* Ibuprofen/Caffeine fixed-dose combination<br>|
| Active Comparator: Ibuprofen<br>Ibuprofen 400 mg | Drug: Ibuprofen<br>* Ibuprofen capsule<br>|
| Placebo Comparator: Placebo<br>Placebo comparator | Drug: Placebo<br>* Placebo treatment<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 (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen | SPRID 0-8: time-weighted sum of PRID scores from 0 to 8 hours. PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Numerical pain severity rating (NPSR) scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible SPRID 0-8 score range: -80 to 112, higher scores = more improvement in pain. | From 0 to 8 hours post-dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8) | SPRID 0-2, SPRID 0-4, SPRID 0-6, SPRID 0-8: time-weighted sum of PRID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours respectively. PRID at each post-dose time point = PID + PRR. PRR score: at each post-dose time point participants answered to question How much relief do you have from your starting pain? on 5-point scale: 0=none, 1=a little, 2=some, 3=a lot, 4=complete; higher scores=more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on 11-point scale: range from 0=no pain to 10=worst possible pain; higher scores=worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value=greater improvement. Score range for: SPRID 0-2= -20 to 28; SPRID 0-4= -40 to 56; SPRID 0-6= -60 to 84; SPRID 0-8= -80 to 112. Higher SPRID scores=more improvement in pain. | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | 
| Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8) | SPID 0-2, SPID 0-4, SPID 0-6, SPID 0-8: time-weighted sum of PID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. NPSR scale: at baseline and each post-dose time point participants answered to question How much pain do you have at this time? on an 11-point scale: score range from 0 = no pain to 10 = worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible range: SPID 0-2 = -20 to 20; SPID 0-4 = -40 to 40; SPID 0-6 = -60 to 60; SPID 0-8 = -80 to 80. Higher SPID scores = more improvement in pain. | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | 
| Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8) | TOTPAR 0-2, TOTPAR 0-4, TOTPAR 0-6, TOTPAR 0-8: time-weighted sum of PRR scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. PRR score: at each post-dose time point participants answered to the question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Overall possible range: TOTPAR 0-2 = 0 to 8; TOTPAR 0-4 = 0 to 16; TOTPAR 0-6 = 0 to 24; TOTPAR 0-8 = 0 to 32. Higher TOTPAR scores = more improvement in pain. | From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1 | 
| Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. At a single post-dose time point overall possible range for PRID score: -10 to 14, higher scores = more improvement in pain. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose on Day 1 | 
| Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | PRR score: at each post-dose time point participants answered to a question How much relief do you have from your starting pain? on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. | 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1 | 
| Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose | NPSR scale: at baseline and each post-dose time point participants answered to a question How much pain do you have at this time? on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a single post-dose time point: -10 to 10, higher positive value = greater improvement in pain. | 0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1 | 
| Time to Onset of Achieving Meaningful Relief | When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as meaningful relief at the moment when they first experienced meaningful relief, that is, when the relief from the pain was meaningful to them. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered). | Up to 8 hours post-dose on Day 1 | 
| Time to Onset of First Perceptible Relief | When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as first perceptible relief and another as meaningful relief. Participants were instructed to stop the stopwatch labelled as first perceptible relief at the moment when they first began to feel any pain relieving effect. It was when they first felt a little/noticeable pain relief. It did not mean that they felt completely better (though they might), but when they first felt any difference in pain that they had at present. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered). | Up to 8 hours post-dose on Day 1 | 
| Time to Treatment Failure | Treatment failure was defined as time to first dose of rescue medication or study discontinuation of the participants due to lack of efficacy. | Up to 8 hours post dose on Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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third molar extraction, ibuprofen, ibuprofen/caffeine, post-surgical dental pain