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A Safety And Efficacy Study of Ibuprofen 250 mg / Acetaminophen 500 mg In The Treatment Of Post-Surgical Dental Pain (SDDP)

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ClinicalTrials.gov Identifier: NCT02912650
Recruitment Status : Completed
First Posted : September 23, 2016
Results First Posted : August 30, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Post-surgical Pain Following Extraction of Molar Teeth Drug: Ibuprofen 250 mg / Acetaminophen 500 mg Drug: Ibuprofen 250 mg Drug: Acetaminophen 650 mg Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 568 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2015
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ibuprofen 250 mg / Acetaminophen 500 mg
2 caplets of Ibuprofen 125 mg / Acetaminophen 250 mg
Drug: Ibuprofen 250 mg / Acetaminophen 500 mg
2 caplets of Ibuprofen 250 mg / Acetaminophen 500 mg
Other Name: IBU 250 / APAP 500

Active Comparator: Ibuprofen 250 mg
2 caplets of IBU 125 mg
Drug: Ibuprofen 250 mg
2 caplets of Ibuprofen 125 mg
Other Name: IBU 250

Active Comparator: Acetaminophen 650 mg
2 tablets of APAP 325 mg
Drug: Acetaminophen 650 mg
2 tablets of Acetaminophen 325 mg
Other Name: APAP 650

Active Comparator: Placebo
2 caplets of Placebo
Drug: Placebo
2 caplets of Placebo




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Time-weighted Sum of Pain Intensity Difference Scores on 11-Point Numerical Scale From 6 to 8 Hours Post-dose (SPID11 [6-8]) [ Time Frame: 6 to 8 hours post-dose ]
    Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11 (6-8): Time-weighted sum of PID scores over 6 to 8 hours. SPID11 score range was -15 (worst score) to 30 (best score) for SPID 6-8. 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).

  2. Time-weighted Sum of Pain Relief Rating (TOTPAR) From 0 to 8 Hours and 6 to 8 Hours Post-dose [ Time Frame: 0 to 8 hours, 6 to 8 hours post-dose ]
    TOTPAR: Time-weighted sum of Pain Relief Rating (PRR) scores over 0 to 8 and 6 to 8 hours. TOTPAR total score range: 0 (worst score) to 32 (best score) for TOTPAR 0-8 and 0 (worst score) to 12 (best score) for TOTPAR 6-8 hours. PRR was assessed on a 5-point categorical pain relief rating scale which ranges from 0 =no relief to 4 =complete relief.

  3. Time to Treatment Failure [ Time Frame: 0 to 12 hours post-dose ]
    Time to treatment failure was defined as the time interval from the study drug administration up to the first documentation of treatment failure. Treatment failure was defined as taking the rescue medication or discontinuation of the participants from the study due to lack of efficacy, whichever came first. Participants were censored at 12 hours or at their final assessment time, whichever came first.

  4. Cumulative Percentage of Participants With Treatment Failure at 6 and 8 Hours [ Time Frame: 6 hours, 8 hours post-dose ]
    Treatment failure was defined as taking the rescue medication or discontinuation of the participants from the study due to lack of efficacy, whichever came first. Participants were censored at 12 hours or at their final assessment time, whichever came first. Percentage of participants who had treatment failure were reported.

  5. Time to Onset of Meaningful Pain Relief [ Time Frame: 0 to 12 hours post-dose ]
    Participants evaluated time to meaningful relief by stopping a second stopwatch labelled as "meaningful relief" at the moment they first began to experience meaningful relief. Stopwatch was active up to 12 hours after dosing or until stopped by participant, or participant became treatment failure prior to depressing the second stopwatch. Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy.


Other Outcome Measures:
  1. Time to Confirmed Onset of First Perceptible Relief [ Time Frame: 0 to 12 hours post-dose ]
    Participants evaluated the time to first perceptible relief (confirmed by meaningful relief) by stopping the first stopwatch labeled 'first perceptible relief' at the moment they first began to experience any pain relief, if the participant also achieved meaningful relief by the end of the study. Stopwatch was active up to 12 hours after dosing or until stopped by the participant, or until the participant dropped out due to treatment failure prior to depressing the first stopwatch or until the time of withdrawal (discontinuation). Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy.

  2. Pain Relief Rating (PRR) Score [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    Participants answered a question: "how much relief do you have from your starting pain?" on a 5-point categorical pain relief rating scale. Scale ranges from 0= no relief to 4= complete relief.

  3. Pain Intensity Difference on 11-Point Numerical Scale (PID11) [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    PID11: baseline pain severity score minus pain severity score at a given time point. Pain intensity was assessed on an 11-point numerical pain severity rating scale. PID11 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 PID11: -5 (worst score) to 10 (best score).

  4. Pain Intensity Difference on 4-Point Categorical Scale (PID4) [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    PID4: baseline pain severity score minus pain severity score at a given time point. Pain intensity was assessed on a 4-point categorical pain severity rating scale. PID4 was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [no pain] to 3 [worst possible pain]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID4: -1 (worst score) to 3 (best score).

  5. Sum of Pain Relief Rating and Pain Intensity Difference on 4-Point Categorical Scale (PRID4) [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    PRID4: sum of PID and PRR at each post-dose time points up to 12 hours. Score range for PRID: -1(worst score) to 7(best score). PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [no pain] to 3 [worst possible pain]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 =worst possible pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID4: -1 (worst score) to 3 (best score). PRR was assessed on a 5-point categorical pain relief rating scale which ranges from 0 =no relief to 4 =complete relief.

  6. 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 [ Time Frame: 0 to 2 hours, 0 to 6 hours, 0 to 12 hours post-dose ]
    Pain intensity was assessed on an 11-point numerical pain severity rating scale. SPID11: Time-weighted sum of PID scores over 12 hours. SPID11 score range was -10 (worst score) to 20 (best score) for SPID 0-2, -30 (worst score) to 60 (best score) for SPID 0-6, -60 (worst score) to 120 (best score) for SPID 0-12. 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) to 10 (best).

  7. 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 [ Time Frame: 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12, 6 to 8 hours post-dose ]
    Pain intensity was assessed on a 4-point categorical pain severity rating scale. SPID4: Time-weighted sum of PID over post-dose time points. SPID4 score range was -2 (worst score) to 6 (best score) for SPID 0-2, -6 (worst score) to 18 (best score) for SPID 0-6, -8 (worst score) to 24 (best score) for SPID 0-8, -12 (worst score) to 36 (best score) for SPID 0-12 and -3 (worst score) to 9 (best score) for SPID 6-8. PID was calculated by subtracting the pain intensity score at given post-dose time points (pain severity score range: 0 [none] to 3 [severe]) from the baseline pain intensity scores (score range: 2 =moderate pain to 3 = severe pain; as participants with baseline pain score of at least moderate were included in study). Total possible score range for PID: -1 (worst score) to 3 (best score).

  8. Time-weighted Sum of Pain Relief Rating (TOTPAR) From 0 to 2 Hours, 0 to 6 Hours and 0 to 12 Hours Post Dose [ Time Frame: 0 to 2 hours, 0 to 6 hours, 0 to 12 hours post-dose ]
    TOTPAR: Time-weighted sum of PRR scores over 2, 6 and 12 hours. TOTPAR total score range: 0 (worst score) to 8 (best score) for TOTPAR 0-2, 0 (worst score) to 24 (best score) for TOTPAR 0-6, 0 (worst score) to 32 (best score) for TOTPAR 0-8, 0 (worst score) to 48 (best score) for TOTPAR 0-12. PRR was assessed on a 5-point categorical pain relief rating scale which ranges from 0 =no relief to 4 =complete relief.

  9. 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 [ Time Frame: 0 to 2 hours, 0 to 6 hours, 0 to 8 hours, 0 to 12, 6 to 8 hours post-dose ]
    SPRID4: Time-weighted sum of PRR and PID based on 4 point categorical pain severity rating scale (PRID) with score range: -2(worst score) to 14 (best score) for SPRID 0-2, -6 (worst score) to 42 (best score) for SPRID 0-6, -8 (worst score) to 56 (best score) for SPRID 0-8, -12 (worst score) to 84 (best score) for SPRID 0-12 and -3 (worst score) to 21 (best score) for SPRID 6-8 hours. PRID: sum of PID and PRR at post-dose time point with score range: -1 (worst score) to 7 (best score). PID calculated by subtracting pain intensity score at post-dose time points (score range: 0 [none] to 3 [severe]) from baseline pain intensity scores (score range: 2 =moderate pain to 3 = severe pain; as participants with baseline score of at least moderate were included). PID total possible score range: -1 (worst score) to 3(best score). PRR assessed on 5-point categorical scale with range: 0 =no relief to 4 =complete relief.

  10. Cumulative Percentage of Participants With Treatment Failure [ Time Frame: 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    Treatment failure was defined as taking the rescue medication or discontinuation of the participants from the study due to lack of efficacy, whichever came first. Participants were censored at 12 hours or at their final assessment time, whichever came first. Percentage of participants who had treatment failure were reported.

  11. Cumulative Percentage of Participants With Confirmed First Perceptible Relief [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    Percentage of participants with confirmed first perceptible relief was reported. Participants evaluated the time to first perceptible relief (confirmed by meaningful relief) by stopping the first stopwatch labelled 'first perceptible relief' at the moment they first began to experience any pain relief, if the participant also achieved meaningful relief by the end of the study. Stopwatch was active up to 12 hours after dosing or until stopped by the participant, or until the participant dropped out due to treatment failure prior to depressing the first stopwatch or until the time of withdrawal (discontinuation). Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy.

  12. Cumulative Percentage of Participants With Meaningful Relief [ Time Frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ]
    Percentage of participants with meaningful relief was reported. Participants evaluated 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 12 hours after dosing or until stopped by participant, or participant became treatment failure prior to depressing the second stopwatch. Treatment failure was defined as participant taking rescue medication, or discontinuing due to lack of efficacy.

  13. Participant's Global Evaluation of Study Medication [ Time Frame: 0 to 12 hours post-dose ]
    Participant global evaluation of study medication was performed at the 12-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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02912650


Locations
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United States, Utah
Jean Brown Research
Salt Lake City, Utah, United States, 84124
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02912650    
Other Study ID Numbers: B5061003
GEMINI SDDP ( Other Identifier: Alias Study Number )
First Posted: September 23, 2016    Key Record Dates
Results First Posted: August 30, 2017
Last Update Posted: August 30, 2017
Last Verified: July 2017
Keywords provided by Pfizer:
ibuprofen
acetaminophen
pain
molar extraction
Additional relevant MeSH terms:
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Toothache
Tooth Diseases
Stomatognathic Diseases
Facial Pain
Pain
Neurologic Manifestations
Acetaminophen
Ibuprofen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action