Study Evaluating A Novel Ibuprofen Formulation In The Treatment Of Dental Pain

Evaluation Of The Efficacy Of A Novel Ibuprofen Formulation In The Treatment Of Post-Surgical Dental Pain: Study I

This study will compare the pain relieving effect of a single-dose of a novel ibuprofen formulation to placebo and two formulations of standard ibuprofen in the treatment of post-surgical dental pain following "wisdom" tooth (third molar) removal.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo; Drug: Novel Ibuprofen; Drug: Standard Ibuprofen

• Study Type: Interventional
• Enrollment (Actual): 335
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Normal, healthy males and females 16 to 40 years of age
• Outpatients who have moderate to severe post-operative pain (confirmed by a Visual Analog Scale-Pain Severity Rating [VAS-PSR] score of at least 50 mm on a 100 mm VAS-PSR) following surgical extraction of two or more third molars, at least one of which must be a partial or complete bony mandibular impaction
• Use of only the following pre-operative medication(s)/anesthetic(s): topical benzocaine, a short acting parenteral (local) anesthetic (mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide

Exclusion Criteria:

• Pregnancy or breast-feeding
• Alcohol or substance abuse
• Any serious medical or psychiatric disorder
• History of stomach ulcers, stomach bleed, or other bleeding disorders
• Use of a prescription or over-the-counter drug with which administration of ibuprofen or any other non-steroidal anti-inflammatory drug, acetaminophen, or hydrocodone is contraindicated (including: opioids, antipsychotics, antianxiety agents, or other central nervous system depressants[including alcohol])

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A	Drug: Novel Ibuprofen; Single-dose of novel ibuprofen (equal to 400 mg ibuprofen)
Active Comparator: Treatment B	Drug: Standard Ibuprofen; Single-dose of standard ibuprofen (400mg)
Active Comparator: Treatment C	Drug: Standard Ibuprofen; Single-dose of standard ibuprofen (400mg)
Placebo Comparator: Treatment D	Drug: Placebo; Single-dose of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-8 Hours (SPRID 0-8)	SPRID: time-weighted sum of pain relief rating combined with pain intensity difference (PRID) over 8 hours. SPRID 0-8 score range: -8 (worst) to 56 (best). PRID: sum of Pain intensity differences (PID) and pain relief rating (PRR) at each time point. PRID score range: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (pain severity score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). PID score range: -1(worst) to 3 (best). PRR: assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief).	0 to 8 hours
Time to Onset of Meaningful Relief	Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment they first began to experience meaningful relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered.	0 to 8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Confirmed First Perceptible Relief	Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment they first began to experience any relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered. The first perceptible relief was considered confirmed if the participant also stopped the second stopwatch indicating meaningful relief.	0 to 8 hours
Pain Relief Rating (PRR)	PRR was evaluated at different time points during the study up to 8 hours after taking the study medication, and immediately before rescue medication was taken (if necessary). PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Pain Intensity Difference (PID)	PID was derived by subtracting the pain severity score at a given post-dosing time point (pain severity score range 0 [none] to 3 [severe]) from the baseline score (Baseline pain severity score range 2 [moderate] to 3 [severe]). Total possible score range for PID: -1 (worst) to 3 (best).	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	PRID was sum of PID and PRR at each post-dosing time point. The overall possible score range, for PRID was -1 (worst) to 7 (best). PID was derived by subtracting the pain severity score at a given post-dosing time point (pain severity score range 0 [none] to 3 [severe]) from the baseline score (Baseline pain severity score range 2 [moderate] to 3 [severe]). Total possible score range for PID: -1 (worst) to 3 (best). PRR was assessed on 5-point categorical pain relief rating scale (0=No relief to 4=Complete relief).	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Time-weighted Sum of Pain Intensity Difference (SPID)	SPID: time-weighted sum of PID over 2, 3, 6 and 8 hours. SPID scores range was -2 (worst) to 6 (best) for SPID 0-2, -3 (worst) to 9 (best) for SPID 0-3, -6 (worst) to 18 (best) for SPID 0-6, -8 (worst) to 24 (best) for SPID 0-8. PID: baseline pain severity score minus pain severity score at a given time point (pain severity score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). Total score range for PID: -1(worst) to 3 (best).	0-2, 0-3, 0-6, 0-8 hours
Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR: time-weighted sum of PRR scores over 2, 3, 6 and 8 hours. TOTPAR score range was 0 (worst) to 8 (best) for TOTPAR 0-2, 0 (worst) to 12 (best) for TOTPAR 0-3, 0 (worst) to 24 (best) for TOTPAR 0-6, 0 (worst) to 32 (best) for TOTPAR 0-8. PRR was evaluated at different time points during the study up to 8 hours, and immediately after taking rescue medication (if necessary). PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.	0-2, 0-3, 0-6, 0-8 hours
Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID: time-weighted sum of PRID over 2, 3, 6 and 8 hours. SPRID score range:-2 (worst) to 14(best) for SPRID 0-2, -3(worst) to 21(best) for SPRID 0-3, -6(worst) to 42(best) for SPRID 0-6, -8(worst) to 56(best) for SPRID 0-8. PRID:sum of PID and PRR at each time point. Total score range for PRID: -1=worst to 7=best. PID:baseline pain severity score minus pain severity score at given time(score range 0=none to 3=severe; baseline score range 2=moderate to 3=severe). Total score range for PID: -1(worst) to 3(best), PRR: scored on 5-point pain relief rating scale(0=No relief to 4=Complete relief).	0-2, 0-3, 0-6, 0-8 hours
Cumulative Percentage of Participants With Meaningful Relief	Percentage of participants with meaningful relief evaluated by stopping the stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Cumulative Percentage of Participants With Confirmed First Perceptible Relief	Percentage of participants with first perceptible relief was evaluated by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 8 hours after dosing or until stopped by the participant, or rescue medication was administered. The first perceptible relief was considered confirmed if the participant also stopped the second stopwatch indicating meaningful relief.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Time to Treatment Failure	Median time of dropping out of the participants from the study due to lack of efficacy or rescue medication, whichever came first.	0 to 8 hours
Cumulative Percentage of Participants With Treatment Failure	Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Cumulative Percentage of Participants With Complete Relief	Complete relief was defined as a PRR of 4. PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8 hours
Participant Global Evaluation of Study Medication	Participant global evaluation of study medication was performed at the 8-hour time point or immediately before taking the rescue medication. It was scored on a 6-point categorical scale where 0 = Very poor, 1 = Poor, 2 = Fair, 3 = Good, 4 = Very Good, and 5 = Excellent.	8 hours

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Jayawardena S, Leyva R, Kellstein D. Safety of a novel formulation of ibuprofen sodium compared with standard ibuprofen and placebo. Postgrad Med. 2015 Jan;127(1):33-7. doi: 10.1080/00325481.2015.993268. Epub 2014 Dec 15.
• Brain P, Leyva R, Doyle G, Kellstein D. Onset of analgesia and efficacy of ibuprofen sodium in postsurgical dental pain: a randomized, placebo-controlled study versus standard ibuprofen. Clin J Pain. 2015 May;31(5):444-50. doi: 10.1097/AJP.0000000000000142.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 1, 2010
• First Submitted That Met QC Criteria: April 1, 2010
• First Posted (Estimate): April 5, 2010

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: July 12, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Pain following third molar extraction
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: AH-09-10