Back to resultsA 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
Primary Purpose
Post Operative Dental Pain
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Diclofenac potassium
Ibuprofen
Placebo to ibuprofen
Placebo to diclofenac potassium
Sponsored by
About this trial
This is an interventional treatment trial for Post Operative Dental Pain focused on measuring Diclofenac potassium, Post-operative dental pain, Moderate to severe pain
Eligibility Criteria
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).
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Dilcofenac potassium + placebo to Ibuprofen
Ibuprofen + placebo to diclofenac potassium
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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'.
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.
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.
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.
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.
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.
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).
Number of Patients Needing Rescue Medication
The number of patients needing rescue medication within the 8 hour treatment period was evaluated.
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).
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Treatment emergent adverse events are reported in the below data table.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02476422
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Operative Dental Pain
Keywords
Diclofenac potassium, Post-operative dental pain, Moderate to severe pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
328 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dilcofenac potassium + placebo to Ibuprofen
Arm Type
Experimental
Arm Description
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.
Arm Title
Ibuprofen + placebo to diclofenac potassium
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Diclofenac potassium
Other Intervention Name(s)
diclofenac-K
Intervention Description
Single dose of diclofenac 50 mg soft gelatin capsule
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Ibuprofen acid
Intervention Description
Single dose of ibuprofen 400 mg tablet
Intervention Type
Drug
Intervention Name(s)
Placebo to ibuprofen
Other Intervention Name(s)
Placebo
Intervention Description
Single dose of placebo to ibuprofen 400 mg tablet
Intervention Type
Drug
Intervention Name(s)
Placebo to diclofenac potassium
Other Intervention Name(s)
Placebo
Intervention Description
Single dose of placebo to diclofenac potassium 50 mg soft gelatin capsule
Primary Outcome Measure Information:
Title
Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at 60 Minutes Post Dose
Description
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.
Time Frame
60 minutes postdose
Secondary Outcome Measure Information:
Title
Change From Baseline in Visual Analog Scale of Pain Intensity (VASPI) at Different Time Points
Description
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.
Time Frame
15, 30, 45, and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours post dose
Title
Area Under the Curve (AUC) of Visual Analog Scale of Pain Intensity (VASPI) Measuring Change From Baseline at Different Time Points
Description
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.
Time Frame
15, 30, 45, 60 and 90 minutes, and 2, 4, 5, 6, 7, and 8 hours post dose
Title
Time to Confirmed First Perceptible Pain Relief
Description
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'.
Time Frame
Within 8 hours postdose
Title
Time to Onset of Meaningful Pain Relief (MPR)
Description
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.
Time Frame
Within 8 hours postdose
Title
Time to Onset of First Perceptible Pain Relief (FPR)
Description
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.
Time Frame
Within 8 hours postdose
Title
Sum of Pain Intensity Difference (SPID)
Description
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 Frame
1, 2, 4, 6, and 8 hours postdose
Title
Summed Total Pain Relief (TOTPAR) at Different Time Points
Description
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.
Time Frame
1, 2, 4, 6, and 8 hours postdose
Title
Peak Analgesic Effect
Description
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.
Time Frame
From dose administration to 8 hours post dose
Title
Duration of Analgesia
Description
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 Frame
From dose administration to 8 hours post dose
Title
Number of Patients Needing Rescue Medication
Description
The number of patients needing rescue medication within the 8 hour treatment period was evaluated.
Time Frame
From dose administration to 8 hours post dose
Title
Number of Patients With Different Responses Based on Patient's Global Assessment of Response to Treatment (PGART)
Description
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).
Time Frame
At 8 hour postdose prior to use of rescue medication
Title
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Description
Treatment emergent adverse events are reported in the below data table.
Time Frame
time of dosage administration up to the follow-up phone call on study Day 3 (maximum 3 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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