Clinical trial NCT02912650: A Safety And Efficacy Study of Ibuprofen 250 mg / Acetaminophen 500 mg In The Treatment Of Post-Surgical Dental Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-surgical Pain Following Extraction of Molar Teeth
Keywords: ibuprofen
acetaminophen
pain
molar extraction
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-09-23
Enrollment: 568
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 0 to 8 Hours Post-dose (SPID11 [0-8])
timeFrame: 0 to 8 hours post-dose
Secondary outcomes:
measure: Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 6 to 8 Hours Post-dose (SPID11 [6-8])
timeFrame: 6 to 8 hours post-dose
measure: Time-weighted Sum of Pain Relief Rating (TOTPAR) From 0 to 8 Hours and 6 to 8 Hours Post-dose
timeFrame: 0 to 8 hours, 6 to 8 hours post-dose
measure: Time to Treatment Failure
timeFrame: 0 to 12 hours post-dose
measure: Cumulative Percentage of Participants With Treatment Failure at 6 and 8 Hours
timeFrame: 6 hours, 8 hours post-dose
measure: Time to Onset of Meaningful Pain Relief
timeFrame: 0 to 12 hours post-dose
Other outcomes:
measure: Time to Confirmed Onset of First Perceptible Relief
timeFrame: 0 to 12 hours post-dose
measure: Pain Relief Rating (PRR) Score
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Pain Intensity Difference on 11-Point Numerical Scale (PID11)
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Pain Intensity Difference on 4-Point Categorical Scale (PID4)
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Sum of Pain Relief Rating and Pain Intensity Difference on 4-Point Categorical Scale (PRID4)
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale (SPID11) From 0 to 2 Hours, 0 to 6 Hours and 0 to 12 Hours Post-dose
timeFrame: 0 to 2 hours, 0 to 6 hours, 0 to 12 hours post-dose
measure: Time-weighted Sum of Pain Intensity Difference Scores on 4-Point Categorical Scale (SPID4) From 0 to 2 Hours, 0 to 6 Hours, 0 to 8 Hours, 0 to 12 Hours and 6 to 8 Hours Post-dose
timeFrame: 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12, 6 to 8 hours post-dose
measure: Time-weighted Sum of Pain Relief Rating (TOTPAR) From 0 to 2 Hours, 0 to 6 Hours and 0 to 12 Hours Post Dose
timeFrame: 0 to 2 hours, 0 to 6 hours, 0 to 12 hours post-dose
measure: Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores on 4-Point Categorical Scale (SPRID4) Over 2, 6, 8, 12 and 6 to 8 Hours Post-dose
timeFrame: 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12, 6 to 8 hours post-dose
measure: Cumulative Percentage of Participants With Treatment Failure
timeFrame: 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Cumulative Percentage of Participants With Confirmed First Perceptible Relief
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Cumulative Percentage of Participants With Meaningful Relief
timeFrame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
measure: Participant's Global Evaluation of Study Medication
timeFrame: 0 to 12 hours post-dose
Locations:
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: