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

Phase 3

Completed

Conditions: Post Operative Dental Pain

Interventions: Drug: Diclofenac potassium
Drug: Ibuprofen
Drug: Placebo to diclofenac potassium
Drug: Placebo to ibuprofen

Registration Number: NCT02476422

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 328

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ibuprofen + placebo to diclofenac potassium	Placebo to diclofenac potassium	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.
Dilcofenac potassium + placebo to Ibuprofen	Placebo to ibuprofen	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.
Dilcofenac potassium + placebo to Ibuprofen	Diclofenac potassium	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.
Ibuprofen + placebo to diclofenac potassium	Ibuprofen	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at 60 Minutes Post Dose	60 minutes postdose	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.

Secondary Outcome Measures

Name	Time	Method
Time to Onset of Meaningful Pain Relief (MPR)	Within 8 hours postdose	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.
Sum of Pain Intensity Difference (SPID)	1, 2, 4, 6, and 8 hours postdose	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.
Time to Onset of First Perceptible Pain Relief (FPR)	Within 8 hours postdose	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.
Duration of Analgesia	From dose administration to 8 hours post dose	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).
Time to Confirmed First Perceptible Pain Relief	Within 8 hours postdose	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'.
Number of Patients With Different Responses Based on Patient's Global Assessment of Response to Treatment (PGART)	At 8 hour postdose prior to use of rescue medication	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).
Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at Different Time Points	15, 30, 45, and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours 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.
Area Under the Curve (AUC) of Visual Analog Scale of Pain Intensity (VASPI) Measuring Change From Baseline at Different Time Points	15, 30, 45, 60 and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours 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 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.
Summed Total Pain Relief (TOTPAR) at Different Time Points	1, 2, 4, 6, and 8 hours postdose	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.
Number of Patients Needing Rescue Medication	From dose administration to 8 hours post dose	The number of patients needing rescue medication within the 8 hour treatment period was evaluated.
Number of Patients With Any Adverse Events, Serious Adverse Events and Death	time of dosage administration up to the follow-up phone call on study Day 3 (maximum 3 days)	Treatment emergent adverse events are reported in the below data table.
Peak Analgesic Effect	From dose administration to 8 hours post dose	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.