A Phase 3, Double-Blind, Randomized, Safety And Efficacy Study Comparing A Single Oral Dose Of Ibuprofen (IBU) 250 Mg/Acetaminophen (APAP) 500 Mg (Administered As Two Tablets Of IBU/APAP 125 Mg/250 Mg) To Each Active Drug Monocomponent Alone And To Placebo In The Treatment Of Post-Surgical Dental Pain
Overview
- Phase
- Phase 3
- Intervention
- Ibuprofen 250 mg / Acetaminophen 500 mg
- Conditions
- Post-surgical Pain Following Extraction of Molar Teeth
- Sponsor
- Pfizer
- Enrollment
- 568
- Locations
- 1
- Primary Endpoint
- Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 0 to 8 Hours Post-dose (SPID11 [0-8])
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a randomized, double blind, placebo-controlled, parallel group, single-center study in approximately 560 subjects to determine the overall analgesic efficacy and safety of a fixed-dose ibuprofen 250 mg / acetaminophen 500 mg formulation compared to ibuprofen 250 mg alone, acetaminophen 650 mg alone, and to placebo. Subjects will be healthy males and females aged 18-40 years, inclusive, who are experiencing post-operative pain following surgical extraction of 3 or more third molar teeth. Following extraction, subjects must experience, within 5 hours, post-surgical pain of at least moderate severity (on a 4-point categorical scale), confirmed by a Visual Analog Pain Severity Rating Scale (VAS PSR) of at least 50 mm on a 100 mm VAS PSR scale. Eligible subjects will be randomized to receive a single oral dose of study medication under double-blind conditions and then evaluated on site for 12 hours following administration of study medication. Subjects will provide self-ratings of pain severity and pain relief at various time points using categorical and numerical scales. Additionally, subjects will also evaluate the time to first perceptible relief and time to meaningful relief using a double stopwatch method. Finally, at 12 hours, subjects will complete a categorical Global Evaluation of the study medication. A review of any reported adverse events will also be completed.
Detailed Description
This is a 12-hour, 4-arm, randomized, double blind, placebo-controlled, parallel group, single-center study in approximately 560 subjects to determine the overall analgesic efficacy and safety of a fixed-dose ibuprofen 250 mg / acetaminophen 500 mg formulation (administered as two caplets of 125 mg/250 mg IBU/APAP) compared to ibuprofen 250 mg alone, acetaminophen 650 mg alone, and to placebo. Subjects will be healthy males and females aged 18-40 years, inclusive, otherwise healthy, who are experiencing post-operative pain following surgical extraction of 3 or more third molar teeth. Following extraction, subjects must experience, within 5 hours, post-surgical pain of at least moderate severity (on a 4-point categorical scale), confirmed by a Visual Analog Pain Severity Rating Scale (VAS PSR) of at least 50 mm on a 100 mm VAS PSR scale. Upon completion of the baseline scales, eligible subjects will be randomized to receive a single oral dose of study medication under double-blind conditions and then evaluated on site for 12 hours following administration of study medication. At 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose time points, subjects will provide: self-ratings of pain severity using the numerical and categorical PSRs; and self-ratings of pain relief at each time point using a categorical pain relief rating scale. At 12 hours, subjects will also complete a 6-point categorical Global Evaluation of the study medication. Additionally, subjects will also evaluate the time to first perceptible relief and time to meaningful relief using a double stopwatch method up to 12 hours post-dose or until the time of first rescue medication use, whichever is sooner. A review of any reported adverse events will also be completed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Outpatients who have undergone surgical extraction of 3 or more third molars, of which at least 2 must be a partial or complete bony mandibular impaction.
- •Subject must have at least moderate pain on the 4-point categorical scale, confirmed by at least 50 mm on the 100 mm VAS PSR scale within approximately 5 hours (i.e., less than or equal to 5 hours, 15 minutes) after surgery is completed.
- •Female subjects are not pregnant or breast feeding.
- •Informed consent.
Exclusion Criteria
- •Presence or history of any significant hepatic, renal, endocrine, cardiovascular, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorder determined by the Investigator to place the subject at increased risk, including the presence or history within 2 years of screening.
- •Acute localized dental alveolar infection at the time of surgery that could confound the post-surgical evaluation.
- •Hypersensitivity to ibuprofen, naproxen, aspirin, or any other NSAID; or to APAP, tramadol, other opioids, or to their combinations.
Arms & Interventions
Ibuprofen 250 mg / Acetaminophen 500 mg
2 caplets of Ibuprofen 125 mg / Acetaminophen 250 mg
Intervention: Ibuprofen 250 mg / Acetaminophen 500 mg
Ibuprofen 250 mg
2 caplets of IBU 125 mg
Intervention: Ibuprofen 250 mg
Acetaminophen 650 mg
2 tablets of APAP 325 mg
Intervention: Acetaminophen 650 mg
Placebo
2 caplets of Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 0 to 8 Hours Post-dose (SPID11 [0-8])
Time Frame: 0 to 8 hours post-dose
Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11 (0-8): Time-weighted sum of pain intensity difference (PID) scores over 8 hours. SPID11 score range was -40 (worst score) to 80 (best score) for SPID 0-8. PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 =no pain to 10 =worst possible pain) from the baseline pain intensity scores (score range: 5 =moderate pain to 10 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -5 (worst score) to 10 (best score).
Secondary Outcomes
- Cumulative Percentage of Participants With Treatment Failure at 6 and 8 Hours(6 hours, 8 hours post-dose)
- Time to Onset of Meaningful Pain Relief(0 to 12 hours post-dose)
- Time-weighted Sum of Pain Relief Rating (TOTPAR) From 0 to 8 Hours and 6 to 8 Hours Post-dose(0 to 8 hours, 6 to 8 hours post-dose)
- Time to Treatment Failure(0 to 12 hours post-dose)
- Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 6 to 8 Hours Post-dose (SPID11 [6-8])(6 to 8 hours post-dose)