Pain
Conditions
Keywords
dental pain, multiple dose, ibuprofen, third molar extraction
Brief summary
The study hypothesis is that single and multiple doses of ibuprofen 600 mg ER caplets provide analgesic efficacy superior to placebo over 12-hour dosing intervals.
Interventions
DRUGPlacebo
One placebo caplet dosed at times 0, 12, 24 and 36 hours
DRUGIbuprofen 600 mg ER
One 600 mg caplet dosed at 0, 12, 24 and 36 hours
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 16 to 40 years of age * Subjects who undergo surgical removal of at least two third molars * One of which must be a partial or full bony mandibular impaction * Subjects must have at least moderate baseline pain (a score of 2 on the categorical pain severity rating scale) confirmed by a score of at least 50 mm on the 100-mm visual analog scale-pain severity rating scale (VAS-PSR)
Exclusion criteria
* Acute localized dental infection at the time of surgery that could confound the post-surgical evaluation * Presence or history of any significant organ disease * Use of prescription or OTC first generation antihistamines * Females who are pregnant, lactating or of childbearing potential and not using a medically approved method to prevent pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Sum of Pain Relief and Pain Intensity Difference Scores From 0 to 12 Hours After the First Dose (SPRID 0-12) | Baseline to 12 hours | SPRID is time-weighted sum of pain relief (PR) plus pain intensity (PI) difference (PID) (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0 equals \[=\] none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for PI: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement in pain intensity. SPRID 0-12 score ranged from -12 to 84; higher score indicated better efficacy. |
| Sum of Pain Relief and Pain Intensity Difference Scores From 8-12 Hours After the First Dose | 8 to 12 hours | SPRID is time-weighted sum of PR plus PID (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPRID 8-12 score ranged from -4 to 28; higher score indicated better efficacy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Taking Rescue Medication | Baseline to 48 hours | Participants not experiencing adequate relief after the 1-hour time point during each dosing interval were allowed to take a single tablet (dose) of acetaminophen/hydrocodone HCl 500 mg/5 mg as a rescue medication (the only rescue medication allowed) during each interval. |
| Pain Relief (PR) Scores | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours | A 5-point categorical pain relief rating scale was used to rate pain relief in response to the question: How much relief do you have from your starting pain? Responses were scored as follows: 0=none, 1=a little, 2=some, 3=a lot, 4=complete. Higher score indicated more pain relief. |
| Pain Intensity Difference (PID) Scores | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 hours | For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale. Responses were scored as follows: 0=none, 1=mild, 2=moderate, 3=severe. PID score=baseline pain intensity score minus score at each time point. PID scores ranged from -1 to 3. Higher positive PID scores indicated greater improvement (decrease in pain intensity). |
| Pain Relief Combined With Pain Intensity (PRID) Scores | 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours | PRID score=PR plus PID. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; PID score ranged from -1 to 3; higher positive PID value=improvement. PRID scores ranged from -1 to 7. Higher PRID scores indicated better pain relief and decrease in pain intensity. |
| Time-weighted Sum of Pain Intensity Difference (SPID) Scores | 0 to 12 hours, 8 to 12 hours, 12 to 24 hours, 20 to 24 hours, 0 to 24 hours, 24 to 36 hours, 32 to 36 hours, 36 to 48 hours, 44 to 48 hours, 24 to 48 hours | SPID is a derived endpoint from PID scores. For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPID scores ranged as follows: 0 to 12 hour (-11.5 to 35.5), 8 to 12 hour (-6.0 to 18.0), 12 to 24 hour (-14.0 to 42.0), 20 to 24 hour (-8.0 to 24.0), 0 to 24 hour (-23.5 to 71.5), 24 to 36 hour (-16.0 to 48.0), 32 to 36 hour (-8.0 to 24.0), 36 to 48 hour (-16.0 to 48.0), 44 to 48 hour (-8.0 to 24.0), 24 to 48 hour (-28.0 to 84.0); higher positive values indicated improvement (decrease) in pain intensity. |
| Number of Doses of Rescue Medication Used | 0-12, 12-24, 24-36, 36-48, 0-48 hours | — |
| Time to Confirmed First Perceptible Relief | Baseline to 12 hours | The elapsed time from dosing until the participant indicated first perceptible pain relief by pressing the first stopwatch, provided the participant also indicated achieving meaningful relief by pressing the second stopwatch. Perceptible relief defined as when participant first began to feel any pain-relieving effect whatsoever of the drug. Did not necessarily mean the participant felt completely better, but when the participant first felt any difference in the pain he/she is currently feeling. |
| Time to Meaningful Relief | Baseline to 12 hours | Participants evaluated the time to meaningful relief by depressing a second stopwatch at the moment they first began to experience meaningful relief, defined as relief from the pain that was considered meaningful to the participant. |
| Participant Global Evaluation Score | 24 and 48 hours | Participants responded, on a 6-point categorical scale, to the following question: How would you rate this medication as a pain-reliever? Responses on this categorical scale ranged as follows: 0=very poor, 1=poor, 2=fair, 3=good, 4=very good, 5=excellent. |
| Time-weighted Sum of Pain Relief Scores (TOTPAR) | 0-12 hours, 8-12 hours | TOTPAR is a derived endpoint from PR scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). TOTPAR 0-12 scores ranged from 0 (worst) to 48 (best). TOTPAR 8-12 scores ranged from 0 (worst) to 16 (best). |
| Time to First Dose of Rescue Medication After First Dose of Study Drug | Baseline to 12 hours | During the first 12 hours of the study, participants not experiencing adequate relief after the 1-hour time point were allowed to take a single tablet (dose) of acetaminophen/hydrocodone hydrochloride (HCl) 500 mg/5 mg as a rescue medication (the only rescue medication allowed). The time at which rescue medication was taken was recorded. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo 1 matching caplet administered orally up to 5 hours after surgery, thereafter every 12 hours up to 48 hours | 52 |
| Ibuprofen Ibuprofen 600 milligrams (mg) extended release (ER) caplet administered orally up to 5 hours after surgery, thereafter every 12 hours up to 48 hours | 54 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Vomited within 4 hours of dosing | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Ibuprofen | Total |
|---|---|---|---|
| Age, Continuous | 21.1 years STANDARD_DEVIATION 3.3 | 21.3 years STANDARD_DEVIATION 3.6 | 21.2 years STANDARD_DEVIATION 3.4 |
| Pain Intensity | 73.8 millimeter STANDARD_DEVIATION 12.25 | 75.7 millimeter STANDARD_DEVIATION 12.18 | 74.8 millimeter STANDARD_DEVIATION 12.2 |
| Pain Severity Moderate | 37 participants | 39 participants | 76 participants |
| Pain Severity Severe | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 33 Participants | 36 Participants | 69 Participants |
| Sex: Female, Male Male | 19 Participants | 18 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 52 | 8 / 54 |
| serious Total, serious adverse events | 0 / 52 | 0 / 54 |
Outcome results
Primary
Sum of Pain Relief and Pain Intensity Difference Scores From 8-12 Hours After the First Dose
SPRID is time-weighted sum of PR plus PID (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPRID 8-12 score ranged from -4 to 28; higher score indicated better efficacy.
Time frame: 8 to 12 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sum of Pain Relief and Pain Intensity Difference Scores From 8-12 Hours After the First Dose | 10.3 units on a scale | Standard Deviation 12 |
| Ibuprofen | Sum of Pain Relief and Pain Intensity Difference Scores From 8-12 Hours After the First Dose | 18.4 units on a scale | Standard Deviation 12.1 |
p-value: <0.00195% CI: [4.13, 12.71]ANOVA
Primary
Time-weighted Sum of Pain Relief and Pain Intensity Difference Scores From 0 to 12 Hours After the First Dose (SPRID 0-12)
SPRID is time-weighted sum of pain relief (PR) plus pain intensity (PI) difference (PID) (PRID) scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0 equals \[=\] none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for PI: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement in pain intensity. SPRID 0-12 score ranged from -12 to 84; higher score indicated better efficacy.
Time frame: Baseline to 12 hours
Population: Intent-to-treat (ITT) population: Randomized participants with at least moderate baseline pain (score 2 on the pain severity rating \[PSR\] scale) confirmed by a score of at least 50 millimeter (mm) on the 100-mm visual analog scale (VAS)-PSR, within approximately 5 hours after surgery, provided a baseline assessment, and received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of Pain Relief and Pain Intensity Difference Scores From 0 to 12 Hours After the First Dose (SPRID 0-12) | 18.2 units on a scale | Standard Deviation 20 |
| Ibuprofen | Time-weighted Sum of Pain Relief and Pain Intensity Difference Scores From 0 to 12 Hours After the First Dose (SPRID 0-12) | 41.5 units on a scale | Standard Deviation 21 |
p-value: <0.00195% CI: [16.45, 31.07]ANOVA
Secondary
Number of Doses of Rescue Medication Used
Time frame: 0-12, 12-24, 24-36, 36-48, 0-48 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Number of Doses of Rescue Medication Used | First dosing interval (0-12 hours) | 1.3 doses | Standard Deviation 1 |
| Placebo | Number of Doses of Rescue Medication Used | Third dosing interval (24-36 hours) | 0.5 doses | Standard Deviation 0.9 |
| Placebo | Number of Doses of Rescue Medication Used | Second dosing interval (12-24 hours) | 0.4 doses | Standard Deviation 0.6 |
| Placebo | Number of Doses of Rescue Medication Used | Fourth dosing interval (36-48 hours) | 0.3 doses | Standard Deviation 0.7 |
| Placebo | Number of Doses of Rescue Medication Used | Overall during the study (0-48 hours) | 2.5 doses | Standard Deviation 2.6 |
| Ibuprofen | Number of Doses of Rescue Medication Used | Fourth dosing interval (36-48 hours) | 0.1 doses | Standard Deviation 0.3 |
| Ibuprofen | Number of Doses of Rescue Medication Used | Overall during the study (0-48 hours) | 0.6 doses | Standard Deviation 1.5 |
| Ibuprofen | Number of Doses of Rescue Medication Used | First dosing interval (0-12 hours) | 0.4 doses | Standard Deviation 0.6 |
| Ibuprofen | Number of Doses of Rescue Medication Used | Second dosing interval (12-24 hours) | 0.1 doses | Standard Deviation 0.2 |
| Ibuprofen | Number of Doses of Rescue Medication Used | Third dosing interval (24-36 hours) | 0.1 doses | Standard Deviation 0.5 |
Comparison: For the first dosing interval.p-value: <0.00195% CI: [-0.91, -0.55]Cochran-Mantel-Haenszel
Comparison: For the second dosing interval.p-value: <0.00195% CI: [-1.05, -0.4]Cochran-Mantel-Haenszel
Comparison: For the third dosing interval.p-value: 0.00295% CI: [-0.9, -0.06]Cochran-Mantel-Haenszel
Comparison: For the fourth dosing interval.p-value: 0.02195% CI: [-1.02, -0.35]Cochran-Mantel-Haenszel
Comparison: For the overall study duration.p-value: <0.00195% CI: [-0.89, -0.51]Cochran-Mantel-Haenszel
Secondary
Pain Intensity Difference (PID) Scores
For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale. Responses were scored as follows: 0=none, 1=mild, 2=moderate, 3=severe. PID score=baseline pain intensity score minus score at each time point. PID scores ranged from -1 to 3. Higher positive PID scores indicated greater improvement (decrease in pain intensity).
Time frame: 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pain Intensity Difference (PID) Scores | 4 hours | 0.1 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 16 hours | 0.7 units on a scale | Standard Deviation 0.9 |
| Placebo | Pain Intensity Difference (PID) Scores | 1.5 hours | 0.0 units on a scale | Standard Deviation 0.9 |
| Placebo | Pain Intensity Difference (PID) Scores | 20 hours | 1.0 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 24 hours | 1.2 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 6 hours | 0.7 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 28 hours | 1.1 units on a scale | Standard Deviation 1.1 |
| Placebo | Pain Intensity Difference (PID) Scores | 1 hour | 0.1 units on a scale | Standard Deviation 0.8 |
| Placebo | Pain Intensity Difference (PID) Scores | 32 hours | 1.0 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 8 hours | 0.4 units on a scale | Standard Deviation 0.9 |
| Placebo | Pain Intensity Difference (PID) Scores | 36 hours | 0.8 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 2 hours | -0.0 units on a scale | Standard Deviation 0.8 |
| Placebo | Pain Intensity Difference (PID) Scores | 40 hours | 0.9 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 10 hours | 0.3 units on a scale | Standard Deviation 0.9 |
| Placebo | Pain Intensity Difference (PID) Scores | 44 hours | 1.3 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 0.5 hours | 0.1 units on a scale | Standard Deviation 0.6 |
| Placebo | Pain Intensity Difference (PID) Scores | 48 hours | 1.4 units on a scale | Standard Deviation 1 |
| Placebo | Pain Intensity Difference (PID) Scores | 12 hours | 0.5 units on a scale | Standard Deviation 1.2 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 48 hours | 1.6 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 0.5 hours | 0.5 units on a scale | Standard Deviation 0.7 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 1 hour | 1.0 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 1.5 hours | 1.2 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 2 hours | 1.4 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 4 hours | 1.4 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 6 hours | 1.3 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 8 hours | 1.0 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 10 hours | 0.9 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 12 hours | 0.8 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 16 hours | 1.6 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 24 hours | 1.2 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 28 hours | 1.6 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 32 hours | 1.6 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 36 hours | 1.0 units on a scale | Standard Deviation 1 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 40 hours | 1.6 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 44 hours | 1.6 units on a scale | Standard Deviation 0.9 |
| Ibuprofen | Pain Intensity Difference (PID) Scores | 20 hours | 1.4 units on a scale | Standard Deviation 0.9 |
Comparison: Ibuprofen versus placebo at 0.5 hours.p-value: <0.00195% CI: [0.16, 0.59]ANOVA
Comparison: Ibuprofen versus placebo at 1 hour.p-value: <0.00195% CI: [0.63, 1.18]ANOVA
Comparison: Ibuprofen versus placebo at 1.5 hours.p-value: <0.00195% CI: [0.91, 1.52]ANOVA
Comparison: Ibuprofen versus placebo at 2 hours.p-value: <0.00195% CI: [1.1, 1.71]ANOVA
Comparison: Ibuprofen versus placebo at 4 hours.p-value: <0.00195% CI: [0.97, 1.67]ANOVA
Comparison: Ibuprofen versus placebo at 6 hours.p-value: <0.00195% CI: [0.3, 0.91]ANOVA
Comparison: Ibuprofen versus placebo at 8 hours.p-value: <0.00195% CI: [0.31, 0.97]ANOVA
Comparison: Ibuprofen versus placebo at 10 hours.p-value: <0.00195% CI: [0.36, 0.97]ANOVA
Comparison: Ibuprofen versus placebo at 12 hours.p-value: 0.08995% CI: [-0.04, 0.59]ANOVA
Comparison: Ibuprofen versus placebo at 16 hours.p-value: <0.00195% CI: [0.7, 1.29]ANOVA
Comparison: Ibuprofen versus placebo at 20 hours.p-value: 0.00495% CI: [0.15, 0.78]ANOVA
Comparison: Ibuprofen versus placebo at 24 hours.p-value: 0.82195% CI: [-0.28, 0.35]ANOVA
Comparison: Ibuprofen versus placebo at 28 hours.p-value: 0.00195% CI: [0.23, 0.9]ANOVA
Comparison: Ibuprofen versus placebo at 32 hours.p-value: <0.00195% CI: [0.3, 0.94]ANOVA
Comparison: Ibuprofen versus placebo at 36 hours.p-value: 0.12795% CI: [-0.07, 0.57]ANOVA
Comparison: Ibuprofen versus placebo at 40 hours.p-value: <0.00195% CI: [0.35, 1]ANOVA
Comparison: Ibuprofen versus placebo at 44 hours.p-value: 0.03695% CI: [0.02, 0.67]ANOVA
Comparison: Ibuprofen versus placebo at 48 hours.p-value: 0.09195% CI: [-0.04, 0.56]ANOVA
Secondary
Pain Relief Combined With Pain Intensity (PRID) Scores
PRID score=PR plus PID. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). 4-point categorical scale for pain intensity: How much pain do you have at this time? (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; PID score ranged from -1 to 3; higher positive PID value=improvement. PRID scores ranged from -1 to 7. Higher PRID scores indicated better pain relief and decrease in pain intensity.
Time frame: 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 1 hour | 0.8 units on a scale | Standard Deviation 1.7 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 6 hours | 2.5 units on a scale | Standard Deviation 2.2 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 2 hours | 0.5 units on a scale | Standard Deviation 1.7 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 8 hours | 1.8 units on a scale | Standard Deviation 2.1 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 1.5 hours | 0.6 units on a scale | Standard Deviation 1.7 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 10 hours | 1.3 units on a scale | Standard Deviation 2 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 4 hours | 0.8 units on a scale | Standard Deviation 2.2 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 12 hours | 2.0 units on a scale | Standard Deviation 2.6 |
| Placebo | Pain Relief Combined With Pain Intensity (PRID) Scores | 0.5 hours | 0.6 units on a scale | Standard Deviation 1.1 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 12 hours | 2.7 units on a scale | Standard Deviation 2.1 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 0.5 hours | 1.8 units on a scale | Standard Deviation 1.6 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 1 hour | 3.2 units on a scale | Standard Deviation 2 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 1.5 hours | 3.8 units on a scale | Standard Deviation 2.2 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 2 hours | 4.1 units on a scale | Standard Deviation 2.1 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 4 hours | 4.3 units on a scale | Standard Deviation 2.2 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 6 hours | 4.0 units on a scale | Standard Deviation 1.9 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 8 hours | 3.5 units on a scale | Standard Deviation 2.2 |
| Ibuprofen | Pain Relief Combined With Pain Intensity (PRID) Scores | 10 hours | 3.0 units on a scale | Standard Deviation 2.2 |
Comparison: Ibuprofen versus placebo at 0.5 hours.p-value: <0.00195% CI: [0.69, 1.74]ANOVA
Comparison: Ibuprofen versus placebo at 1 hour.p-value: <0.00195% CI: [1.77, 3.09]ANOVA
Comparison: Ibuprofen versus placebo at 1.5 hours.p-value: <0.00195% CI: [2.49, 3.95]ANOVA
Comparison: Ibuprofen versus placebo at 2 hours.p-value: <0.00195% CI: [2.98, 4.42]ANOVA
Comparison: Ibuprofen versus placebo at 4 hours.p-value: <0.00195% CI: [2.67, 4.33]ANOVA
Comparison: Ibuprofen versus placebo at 6 hours.p-value: <0.00195% CI: [0.79, 2.27]ANOVA
Comparison: Ibuprofen versus placebo at 8 hours.p-value: <0.00195% CI: [0.87, 2.48]ANOVA
Comparison: Ibuprofen versus placebo at 10 hours.p-value: <0.00195% CI: [0.97, 2.54]ANOVA
Comparison: Ibuprofen versus placebo at 12 hours.p-value: 0.05695% CI: [-0.02, 1.58]ANOVA
Secondary
Pain Relief (PR) Scores
A 5-point categorical pain relief rating scale was used to rate pain relief in response to the question: How much relief do you have from your starting pain? Responses were scored as follows: 0=none, 1=a little, 2=some, 3=a lot, 4=complete. Higher score indicated more pain relief.
Time frame: 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pain Relief (PR) Scores | 1 hour | 0.7 units on a scale | Standard Deviation 1 |
| Placebo | Pain Relief (PR) Scores | 6 hours | 1.9 units on a scale | Standard Deviation 1.3 |
| Placebo | Pain Relief (PR) Scores | 2 hours | 0.5 units on a scale | Standard Deviation 1 |
| Placebo | Pain Relief (PR) Scores | 8 hours | 1.4 units on a scale | Standard Deviation 1.3 |
| Placebo | Pain Relief (PR) Scores | 1.5 hours | 0.6 units on a scale | Standard Deviation 1 |
| Placebo | Pain Relief (PR) Scores | 10 hours | 1.0 units on a scale | Standard Deviation 1.3 |
| Placebo | Pain Relief (PR) Scores | 4 hours | 0.7 units on a scale | Standard Deviation 1.3 |
| Placebo | Pain Relief (PR) Scores | 12 hours | 1.5 units on a scale | Standard Deviation 1.5 |
| Placebo | Pain Relief (PR) Scores | 0.5 hours | 0.4 units on a scale | Standard Deviation 0.7 |
| Ibuprofen | Pain Relief (PR) Scores | 12 hours | 1.9 units on a scale | Standard Deviation 1.3 |
| Ibuprofen | Pain Relief (PR) Scores | 0.5 hours | 1.3 units on a scale | Standard Deviation 1.1 |
| Ibuprofen | Pain Relief (PR) Scores | 1 hour | 2.2 units on a scale | Standard Deviation 1.2 |
| Ibuprofen | Pain Relief (PR) Scores | 1.5 hours | 2.6 units on a scale | Standard Deviation 1.3 |
| Ibuprofen | Pain Relief (PR) Scores | 2 hours | 2.8 units on a scale | Standard Deviation 1.2 |
| Ibuprofen | Pain Relief (PR) Scores | 4 hours | 2.9 units on a scale | Standard Deviation 1.3 |
| Ibuprofen | Pain Relief (PR) Scores | 6 hours | 2.8 units on a scale | Standard Deviation 1.1 |
| Ibuprofen | Pain Relief (PR) Scores | 8 hours | 2.4 units on a scale | Standard Deviation 1.3 |
| Ibuprofen | Pain Relief (PR) Scores | 10 hours | 2.1 units on a scale | Standard Deviation 1.4 |
Comparison: Ibuprofen versus placebo at 0.5 hours.p-value: <0.00195% CI: [0.5, 1.19]ANOVA
Comparison: Ibuprofen versus placebo at 1 hour.p-value: <0.00195% CI: [1.11, 1.94]ANOVA
Comparison: Ibuprofen versus placebo at 1.5 hours.p-value: <0.00195% CI: [1.56, 2.44]ANOVA
Comparison: Ibuprofen versus placebo at 2 hours.p-value: <0.00195% CI: [1.86, 2.73]ANOVA
Comparison: Ibuprofen versus placebo at 4 hours.p-value: <0.00195% CI: [1.69, 2.68]ANOVA
Comparison: Ibuprofen versus placebo at 6 hours.p-value: <0.00195% CI: [0.46, 1.38]ANOVA
Comparison: Ibuprofen versus placebo at 8 hours.p-value: <0.00195% CI: [0.54, 1.54]ANOVA
Comparison: Ibuprofen versus placebo at 10 hours.p-value: <0.00195% CI: [0.59, 1.6]ANOVA
Comparison: Ibuprofen versus placebo at 12 hours.p-value: 0.05295% CI: [0, 1.01]ANOVA
Secondary
Participant Global Evaluation Score
Participants responded, on a 6-point categorical scale, to the following question: How would you rate this medication as a pain-reliever? Responses on this categorical scale ranged as follows: 0=very poor, 1=poor, 2=fair, 3=good, 4=very good, 5=excellent.
Time frame: 24 and 48 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Participant Global Evaluation Score | 24 hours | 1.2 units on a scale | Standard Deviation 1.4 |
| Placebo | Participant Global Evaluation Score | 48 hours | 1.7 units on a scale | Standard Deviation 1.5 |
| Ibuprofen | Participant Global Evaluation Score | 24 hours | 3.5 units on a scale | Standard Deviation 1.2 |
| Ibuprofen | Participant Global Evaluation Score | 48 hours | 3.7 units on a scale | Standard Deviation 1 |
Comparison: Ibuprofen versus placebo at 24 hoursp-value: <0.00195% CI: [0.74, 0.95]Cochran-Mantel-Haenszel
Comparison: Ibuprofen versus placebo at 48 hoursp-value: <0.00195% CI: [0.66, 0.92]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Taking Rescue Medication
Participants not experiencing adequate relief after the 1-hour time point during each dosing interval were allowed to take a single tablet (dose) of acetaminophen/hydrocodone HCl 500 mg/5 mg as a rescue medication (the only rescue medication allowed) during each interval.
Time frame: Baseline to 48 hours
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Taking Rescue Medication | Second dosing interval (12 to 24 hours) | 30.8 percentage of participants |
| Placebo | Percentage of Participants Taking Rescue Medication | Fourth dosing interval (36 to 48 hours) | 19.2 percentage of participants |
| Placebo | Percentage of Participants Taking Rescue Medication | Third dosing interval (24 to 36 hours) | 32.7 percentage of participants |
| Placebo | Percentage of Participants Taking Rescue Medication | Overall during the study (0 to 48 hours) | 78.8 percentage of participants |
| Placebo | Percentage of Participants Taking Rescue Medication | First dosing interval (0 to 12 hours) | 76.9 percentage of participants |
| Ibuprofen | Percentage of Participants Taking Rescue Medication | Overall during the study (0 to 48 hours) | 31.5 percentage of participants |
| Ibuprofen | Percentage of Participants Taking Rescue Medication | First dosing interval (0 to 12 hours) | 29.6 percentage of participants |
| Ibuprofen | Percentage of Participants Taking Rescue Medication | Second dosing interval (12 to 24 hours) | 5.6 percentage of participants |
| Ibuprofen | Percentage of Participants Taking Rescue Medication | Third dosing interval (24 to 36 hours) | 9.3 percentage of participants |
| Ibuprofen | Percentage of Participants Taking Rescue Medication | Fourth dosing interval (36 to 48 hours) | 5.6 percentage of participants |
Comparison: During the first dosing interval (0 to 12 hours).p-value: <0.00195% CI: [-64.46, -31.56]Cochran-Mantel-Haenszel
Comparison: During the second dosing interval (12 to 24 hours).p-value: <0.00195% CI: [-39.78, -11.28]Cochran-Mantel-Haenszel
Comparison: During the third dosing interval (24 to 36 hours).p-value: 0.00295% CI: [-38.93, -9.18]Cochran-Mantel-Haenszel
Comparison: During the fourth dosing interval (36 to 48 hours).p-value: 0.03595% CI: [-26.41, -0.79]Cochran-Mantel-Haenszel
Comparison: During the study overall (0 to 48 hours).p-value: <0.00195% CI: [-64.42, -31.6]Cochran-Mantel-Haenszel
Comparison: Time to First Dose Rescue Medication Over Entire Study Period (0-48 Hours)p-value: 0.01195% CI: [0.01, 0.57]Andersen-Gill (AG)
Secondary
Time to Confirmed First Perceptible Relief
The elapsed time from dosing until the participant indicated first perceptible pain relief by pressing the first stopwatch, provided the participant also indicated achieving meaningful relief by pressing the second stopwatch. Perceptible relief defined as when participant first began to feel any pain-relieving effect whatsoever of the drug. Did not necessarily mean the participant felt completely better, but when the participant first felt any difference in the pain he/she is currently feeling.
Time frame: Baseline to 12 hours
Population: ITT population. Here, Number of participants analysed signifies those participants who were evaluable for this outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Confirmed First Perceptible Relief | NA minutes |
| Ibuprofen | Time to Confirmed First Perceptible Relief | 25.0 minutes |
Secondary
Time to First Dose of Rescue Medication After First Dose of Study Drug
During the first 12 hours of the study, participants not experiencing adequate relief after the 1-hour time point were allowed to take a single tablet (dose) of acetaminophen/hydrocodone hydrochloride (HCl) 500 mg/5 mg as a rescue medication (the only rescue medication allowed). The time at which rescue medication was taken was recorded.
Time frame: Baseline to 12 hours
Population: ITT population. Here, Number of participants analysed signifies those participants who were evaluable for this outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Dose of Rescue Medication After First Dose of Study Drug | 1.6 hours |
| Ibuprofen | Time to First Dose of Rescue Medication After First Dose of Study Drug | NA hours |
p-value: <0.00195% CI: [0.1, 0.34]proportional hazards model
Secondary
Time to Meaningful Relief
Participants evaluated the time to meaningful relief by depressing a second stopwatch at the moment they first began to experience meaningful relief, defined as relief from the pain that was considered meaningful to the participant.
Time frame: Baseline to 12 hours
Population: ITT population. Here, Number of participants analysed signifies those participants who were evaluable for this outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Meaningful Relief | NA minutes |
| Ibuprofen | Time to Meaningful Relief | 54.2 minutes |
Secondary
Time-weighted Sum of Pain Intensity Difference (SPID) Scores
SPID is a derived endpoint from PID scores. For pain intensity, How much pain do you have at this time? answered on a 4-point categorical scale (0=none, 1=mild, 2=moderate, 3=severe). PID score=baseline pain intensity score minus pain intensity at each time point; score ranged from -1 to 3; higher positive PID value indicated improvement (decrease) in pain intensity. SPID scores ranged as follows: 0 to 12 hour (-11.5 to 35.5), 8 to 12 hour (-6.0 to 18.0), 12 to 24 hour (-14.0 to 42.0), 20 to 24 hour (-8.0 to 24.0), 0 to 24 hour (-23.5 to 71.5), 24 to 36 hour (-16.0 to 48.0), 32 to 36 hour (-8.0 to 24.0), 36 to 48 hour (-16.0 to 48.0), 44 to 48 hour (-8.0 to 24.0), 24 to 48 hour (-28.0 to 84.0); higher positive values indicated improvement (decrease) in pain intensity.
Time frame: 0 to 12 hours, 8 to 12 hours, 12 to 24 hours, 20 to 24 hours, 0 to 24 hours, 24 to 36 hours, 32 to 36 hours, 36 to 48 hours, 44 to 48 hours, 24 to 48 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 0-12 | 4.1 units on a scale | Standard Deviation 9.6 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 8-12 | 2.5 units on a scale | Standard Deviation 5.4 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 12-24 | 12.5 units on a scale | Standard Deviation 12.5 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 20-24 | 8.8 units on a scale | Standard Deviation 7.5 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 0-24 | 15.5 units on a scale | Standard Deviation 19.3 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 24-36 | 16.2 units on a scale | Standard Deviation 15.2 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 32-36 | 7.0 units on a scale | Standard Deviation 7.8 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 36-48 | 17.4 units on a scale | Standard Deviation 14.2 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 44-48 | 10.5 units on a scale | Standard Deviation 7.7 |
| Placebo | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 24-48 | 30.5 units on a scale | Standard Deviation 25.2 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 36-48 | 23.0 units on a scale | Standard Deviation 13.8 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 0-12 | 12.8 units on a scale | Standard Deviation 9.5 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 24-36 | 21.6 units on a scale | Standard Deviation 13.9 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 8-12 | 5.5 units on a scale | Standard Deviation 5.2 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 24-48 | 40.7 units on a scale | Standard Deviation 23.9 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 12-24 | 18.7 units on a scale | Standard Deviation 11.7 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 32-36 | 10.2 units on a scale | Standard Deviation 7.4 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 20-24 | 10.7 units on a scale | Standard Deviation 7.3 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 44-48 | 12.7 units on a scale | Standard Deviation 7.3 |
| Ibuprofen | Time-weighted Sum of Pain Intensity Difference (SPID) Scores | SPID 0-24 | 29.9 units on a scale | Standard Deviation 18.8 |
Comparison: For SPID 0-12.p-value: <0.00195% CI: [5.94, 11.95]ANOVA
Comparison: For SPID 8-12.p-value: <0.00195% CI: [1.45, 4.85]ANOVA
Comparison: For SPID 12-24.p-value: <0.00195% CI: [2.84, 10.27]ANOVA
Comparison: For SPID 20-24.p-value: 0.09195% CI: [-0.33, 4.37]ANOVA
Comparison: For SPID 0-24.p-value: <0.00195% CI: [9.12, 20.79]ANOVA
Comparison: For SPID 24-36.p-value: 0.0195% CI: [1.42, 10.33]ANOVA
Comparison: For SPID 32-36.p-value: 0.00495% CI: [1.13, 5.83]ANOVA
Comparison: For SPID 36-48.p-value: 0.00695% CI: [1.82, 10.36]ANOVA
Comparison: For SPID 44-48.p-value: 0.04295% CI: [0.09, 4.73]ANOVA
Comparison: For SPID 24-48.p-value: 0.00495% CI: [3.49, 18.45]ANOVA
Secondary
Time-weighted Sum of Pain Relief Scores (TOTPAR)
TOTPAR is a derived endpoint from PR scores. 5-point categorical scale for PR: How much relief do you have from your starting pain? (0=none, 1=a little, 2=some, 3=a lot, 4=complete). TOTPAR 0-12 scores ranged from 0 (worst) to 48 (best). TOTPAR 8-12 scores ranged from 0 (worst) to 16 (best).
Time frame: 0-12 hours, 8-12 hours
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time-weighted Sum of Pain Relief Scores (TOTPAR) | TOTPAR 0 to 12 | 14.1 units on a scale | Standard Deviation 11.2 |
| Placebo | Time-weighted Sum of Pain Relief Scores (TOTPAR) | TOTPAR 8 to 12 | 7.8 units on a scale | Standard Deviation 7.2 |
| Ibuprofen | Time-weighted Sum of Pain Relief Scores (TOTPAR) | TOTPAR 0 to 12 | 28.7 units on a scale | Standard Deviation 12.3 |
| Ibuprofen | Time-weighted Sum of Pain Relief Scores (TOTPAR) | TOTPAR 8 to 12 | 12.9 units on a scale | Standard Deviation 7.4 |
Comparison: Ibuprofen versus placebo at 0 to 12 hours.p-value: <0.00195% CI: [10.38, 19.25]ANOVA
Comparison: Ibuprofen versus placebo from 8 to 12 hours.p-value: <0.00195% CI: [2.57, 7.98]ANOVA