A Study to Assess the Efficacy and Tolerability of Diclofenac Potassium Soft Gelatin Capsules Compared With Ibuprofen Tablets in Patients With Moderate to Severe Postoperative Dental Pain

Study Overview
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Brief Summary
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The study is designed to assess the efficacy and tolerability of diclofenac potassium soft gelatin capsules compared with ibuprofen tablets in patients with moderate to severe postoperative dental pain.

Official Title
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A Randomized, Double-blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Tolerability of 50 mg Diclofenac Potassium Soft Gelatin Capsules Compared With 400 mg Ibuprofen Tablets in Patients With Moderate to Severe Postoperative Dental Pain

Conditions
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Post Operative Dental Pain

Intervention / Treatment
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* Drug: Diclofenac potassium
* Drug: Ibuprofen
* Drug: Placebo to ibuprofen
* Drug: Placebo to diclofenac potassium


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients requiring surgical removal of 2 ipsilateral third molars, of which the mandibular must be fully or partially impacted. The ipsilateral maxillary third molar may be of any impaction level. Patients having a moderate to severe Baseline pain intensity as assessed by a score of 2 (moderate) or 3 (severe) on the 4-point categorical pain intensity VRS, confirmed by a VASPI score of ≥ 50 mm within 5 hours of surgical completion, after local anesthetic dissipation. Key Exclusion Criteria: Patients who require the removal of a single third molar, or 2 ipsilateral third molars where mandibular molar is not fully or partially impacted. Patients with active peptic ulcer disease or a history of significant gastrointestinal disease or any gastrointestinal bleeding. Patients with coagulation or bleeding disorders. Patients with a positive drug or alcohol screen. Patients who have received an anti-inflammatory agent, analgesic, sedative, hypnotic, muscle relaxant, or tranquilizer within 5 elimination half-lives before administration of study drug (other than surgical anesthetic prior to and during dental surgery).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Dilcofenac potassium + placebo to Ibuprofen<br>Single dose of diclofenac potassium 50 mg soft gelatin capsule was given once patient developed moderate to severe pain post the extraction of two ipsilateral third molar teeth. Single dose of placebo to ibuprofen 400 mg tablet was also given to patient in order to maintain double dummy method. | Drug: Diclofenac potassium<br>* Single dose of diclofenac 50 mg soft gelatin capsule<br>* Other names: diclofenac-K;Drug: Placebo to ibuprofen<br>* Single dose of placebo to ibuprofen 400 mg tablet<br>* Other names: Placebo;|
| Active Comparator: Ibuprofen + placebo to diclofenac potassium<br>Single dose of ibuprofen 400 mg tablet was given once patient develops moderate to severe pain post the extraction of two ipsilateral third molar teeth. Single dose of placebo to diclofenac potassium 50 mg soft gelatin capsule was also given to patient in order to maintain double dummy method. | Drug: Ibuprofen<br>* Single dose of ibuprofen 400 mg tablet<br>* Other names: Ibuprofen acid;Drug: Placebo to diclofenac potassium<br>* Single dose of placebo to diclofenac potassium 50 mg soft gelatin capsule<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at 60 Minutes Post Dose | VASPI reduction from baseline is the difference between the Baseline VASPI score and the VASPI score at a specific observation point. Subjects were asked to identify their current level of pain intensity on the 100 mm VASPI, labeled no pain (0 mm) as the left anchor and worst possible pain (100 mm) as the right anchor. A positive change represents a reduction in pain. | 60 minutes postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at Different Time Points | VASPI reduction from baseline is the difference between the Baseline VASPI score and the VASPI score at a specific observation point. Subjects were asked to identify their current level of pain intensity on the 100 mm VASPI, labeled no pain (0 mm) as the left anchor and worst possible pain (100 mm) as the right anchor. A positive change represents a reduction in pain. | 15, 30, 45, and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours post dose | 
| Area Under the Curve (AUC) of Visual Analog Scale of Pain Intensity (VASPI) Measuring Change From Baseline at Different Time Points | VASPI reduction from baseline is the difference between the Baseline VASPI score and the VASPI score at a specific observation point. Subjects were asked to identify their pain intensity using the 100 mm VASPI to indicate their current level of pain intensity on the 100 mm VASPI labeled no pain (0 mm) as the left anchor and worst possible pain (100 mm) as the right anchor. A positive change shows reduction in pain. AUC of VASPI reduction from baseline for each time point was calculated using the trapezoidal rule. | 15, 30, 45, 60 and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours post dose | 
| Time to Confirmed First Perceptible Pain Relief | Time to onset of first perceptible pain relief (FPR), provided the FPR was subsequently 'confirmed' through the achievement of meaningful pain relief (MPR). Participant started two stopwatches at dosing, and recorded FPR by stopping the first stopwatch when he/she first experienced 'any' pain relief. FPR is 'confirmed' only if the participant also stopped the second stopwatch indicating 'meaningful pain relief'. | Within 8 hours postdose | 
| Time to Onset of Meaningful Pain Relief (MPR) | Using the double stopwatch technique, participant started two stopwatches at dosing, and stopped the second stopwatch as soon as he/she began to experience 'meaningful' relief from pain. Time elapsed is recorded as the MPR. | Within 8 hours postdose | 
| Time to Onset of First Perceptible Pain Relief (FPR) | Using the double stopwatch technique, participant started two stopwatches at dosing, and stopped the first stopwatch as soon as he/she first began to feel 'any' relief from pain. The time elapsed was recorded as the FPR. | Within 8 hours postdose | 
| Sum of Pain Intensity Difference (SPID) | At baseline and at each defined study time point, the clinical site staff captured pain intensity information from each subject using the 4-point categorical VRS. The subject was asked What is your pain level at this time? and the response was recorded as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Pain intensity difference (PID) was the difference between the baseline pain intensity score and the pain intensity score at a specific observation point. SPID is the weighted sum of PIDs from the 15-minute to the 8-hour observation point (SPID8). Additionally, SPID evaluations were also be done at 1 (SPID1), 2 (SPID2), 4 (SPID4) and 6 (SPID6) hours post dose. The weights used for these values were 0.25 for the 15-, 30-, 45-, and 60-minute observations, and 0.5 for the 90-minute, 2- and 4-hour observations, and 1 for the remaining observations. | 1, 2, 4, 6, and 8 hours postdose | 
| Summed Total Pain Relief (TOTPAR) at Different Time Points | After the administration of the single dose of the assigned study treatment, at the defined study time points, the clinical site staff captured pain relief information from each subject. The subject was asked What is the amount of pain relief as compared to the starting pain? and the response was recorded as 0 = none, 1 = a little, 2 = some, 3 = a lot, or 4 = complete. Total pain relief (TOTPAR) was the weighted sum of the pain relief scores from the 15-minute to the 8-hour observation points (TOTPAR8). Additionally, TOTPARs at 1, 2, 4 and 6 hours were calculated. The weights used for these values (evaluation time points) were 0.25 for the 15-, 30-, 45-, and 60-minute observations, 0.5 for the 90-minute, 2- and 4-hour observations, and 1 for the remaining observations. | 1, 2, 4, 6, and 8 hours postdose | 
| Peak Analgesic Effect | Peak analgesic relief is represented through highest pain intensity difference (PID), highest VASPI reduction, and highest pain relief scores. Pain intensity was measured on a verbal rating scale (VRS) ranging from 0 to 3 (none to severe, with higher score for higher pain intensity). PID represents difference in this score at baseline and specific time points, larger change indicating larger reduction in pain, with highest PID representing the largest difference. Pain relief was recorded on a scale ranging from 0 to 4 (none to complete, with higher score for higher pain relief), with highest pain relief representing maximum relief obtained. Pain intensity was also measured through a 100 mm visual analogue scale (VASPI), ranging from no pain (0 mm) to worst possible pain (100 mm). A positive change in VASPI indicates reduction in pain, with highest VASPI reduction representing highest change. | From dose administration to 8 hours post dose | 
| Duration of Analgesia | Duration of analgesia (time to first use of rescue medication) was evaluated, from dose administration to the time of first use of rescue medication within the 8-hour treatment period. Censored observations were included in calculating this endpoint. Censored subjects include any subject who did not take rescue medication prior to the end of the assessment period of 480 minutes (8 hours). | From dose administration to 8 hours post dose | 
| Number of Patients Needing Rescue Medication | The number of patients needing rescue medication within the 8 hour treatment period was evaluated. | From dose administration to 8 hours post dose | 
| Number of Patients With Different Responses Based on Patient's Global Assessment of Response to Treatment (PGART) | PGART was measured by asking patients to give a score on a scale from 0 to 4, where 0 = poor; 1 = fair; 2 = good; 3 = very good; 4 = excellent. This measurement was taken at the end of 8 hours, or before the use of rescue medication (for a patient who takes rescue medciation within the 8 hour period). | At 8 hour postdose prior to use of rescue medication | 
| Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Treatment emergent adverse events are reported in the below data table. | time of dosage administration up to the follow-up phone call on study Day 3 (maximum 3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diclofenac potassium, Post-operative dental pain, Moderate to severe pain