Pain, Postoperative
Conditions
Keywords
Postsurgical pain
Brief summary
To compare the duration of analgesic efficacy as determined by the time to rescue medication of a single oral dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo over 24 hours in subjects experiencing moderate to severe post-impaction surgery dental pain. To compare the overall analgesic effect (SPID 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo. To compare the overall relief from pain (TOTPAR 0-24) of a single dose of naproxen sodium 440 mg (2 x 220 mg tablets) relative to ibuprofen 400 mg (2 x 200 mg tablets) and placebo.
Interventions
220 mg x 2 tablets, oral, single dose
200 mg x 2 tablets, oral, single dose
DRUGPlacebo
Matching placebo, 2 tablets, oral, single dose
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Healthy, ambulatory, male or female volunteers 16-40 years of age; * Body mass index 18.0 to 30.0 kg/m\^2 inclusive; * Scheduled to undergo surgical removal of at least 2 mandibular partial or full bony impacted third molars. Up to two maxillary third molars may be removed regardless of impaction level. Supernumerary teeth present may also be removed at the discretion of the oral surgeon; * Mandibular molars must demonstrate modified Demirjian root classification stage D, E, F, G or H;
Exclusion criteria
* History of hypersensitivity to naproxen sodium, ibuprofen, nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational products; * Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years; * Relevant concomitant disease such as asthma (exercise induced asthma is permitted)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Use of Rescue Medication | Up to 24 hours | Time to first use of rescue medication was estimated using Kaplan-Meier method. If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference (SPID) | Up to 24 hours | Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted sum of pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. |
| Total Pain Relief (TOTPAR) | Up to 24 hours | Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at one center in the United States, between 12 February 2018 (first patient first visit) and 10 July 2018 (last patient last visit).
Pre-assignment details
Overall, 387 participants completed surgical teeth extraction, and all of them were randomized and received the treatment.
Participants by arm
| Arm | Count |
|---|---|
| Naproxen Sodium (Aleve, BAY117031) Participants received one single dose of 440 mg naproxen sodium tablets (200 mg x 2 tablets, oral) after randomization | 166 |
| Ibuprofen (Advil) Participants received one single dose of 400 mg ibuprofen tablets (200 mg x 2 tablets, oral) after randomization | 166 |
| Placebo Participants received one single dose of matching placebo tablets (2 tablets, oral) after randomization | 55 |
| Total | 387 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Naproxen Sodium (Aleve, BAY117031) | Ibuprofen (Advil) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 19.0 years STANDARD_DEVIATION 2.96 | 19.0 years STANDARD_DEVIATION 2.62 | 19.0 years STANDARD_DEVIATION 2.91 | 19.0 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 25 Participants | 10 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 143 Participants | 141 Participants | 45 Participants | 329 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity Score Mild Pain (1) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity Score Moderate Pain (2) | 69 Participants | 67 Participants | 23 Participants | 159 Participants |
| Pain Intensity Score No Pain (0) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity Score Severe Pain (3) | 97 Participants | 99 Participants | 32 Participants | 228 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 5 Participants | 2 Participants | 18 Participants |
| Race/Ethnicity, Customized White | 148 Participants | 148 Participants | 48 Participants | 344 Participants |
| Sex: Female, Male Female | 77 Participants | 89 Participants | 30 Participants | 196 Participants |
| Sex: Female, Male Male | 89 Participants | 77 Participants | 25 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 166 | 0 / 55 | 0 / 166 |
| other Total, other adverse events | 25 / 166 | 16 / 55 | 31 / 166 |
| serious Total, serious adverse events | 1 / 166 | 0 / 55 | 0 / 166 |
Outcome results
Primary
Time to First Use of Rescue Medication
Time to first use of rescue medication was estimated using Kaplan-Meier method. If a subject did not take the rescue medication during the treatment period, (s)he was censored at the time of last assessment.
Time frame: Up to 24 hours
Population: Per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naproxen Sodium (Aleve, BAY117031) | Time to First Use of Rescue Medication | 75th Percentile | NA hours |
| Naproxen Sodium (Aleve, BAY117031) | Time to First Use of Rescue Medication | 50th Percentile | NA hours |
| Naproxen Sodium (Aleve, BAY117031) | Time to First Use of Rescue Medication | Minimum | 1.22 hours |
| Naproxen Sodium (Aleve, BAY117031) | Time to First Use of Rescue Medication | 25th Percentile | 11.017 hours |
| Naproxen Sodium (Aleve, BAY117031) | Time to First Use of Rescue Medication | Maximum | 22.17 hours |
| Ibuprofen (Advil) | Time to First Use of Rescue Medication | 50th Percentile | 10.533 hours |
| Ibuprofen (Advil) | Time to First Use of Rescue Medication | Minimum | 1.22 hours |
| Ibuprofen (Advil) | Time to First Use of Rescue Medication | 25th Percentile | 8.267 hours |
| Ibuprofen (Advil) | Time to First Use of Rescue Medication | 75th Percentile | 14.117 hours |
| Ibuprofen (Advil) | Time to First Use of Rescue Medication | Maximum | 18.28 hours |
| Placebo | Time to First Use of Rescue Medication | Maximum | 21.75 hours |
| Placebo | Time to First Use of Rescue Medication | 75th Percentile | 12.100 hours |
| Placebo | Time to First Use of Rescue Medication | Minimum | 1.18 hours |
| Placebo | Time to First Use of Rescue Medication | 50th Percentile | 2.533 hours |
| Placebo | Time to First Use of Rescue Medication | 25th Percentile | 2.117 hours |
p-value: <0.001Log Rank
p-value: <0.001Log Rank
Secondary
Sum of Pain Intensity Difference (SPID)
Pain intensity was measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each postdose time point, pain intensity differences (PIDs) were derived by subtracting the pain intensity at the postdose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference was indicative of improvement. Time-weighted sum of pain intensity differences (SPIDs) were calculated by multiplying the PID score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.
Time frame: Up to 24 hours
Population: Per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium (Aleve, BAY117031) | Sum of Pain Intensity Difference (SPID) | 83.29 Scores on a scale * hours | Standard Deviation 57.177 |
| Ibuprofen (Advil) | Sum of Pain Intensity Difference (SPID) | 48.54 Scores on a scale * hours | Standard Deviation 40.705 |
| Placebo | Sum of Pain Intensity Difference (SPID) | 9.96 Scores on a scale * hours | Standard Deviation 58.197 |
95% CI: [-45.67, -23.8]ANCOVA
95% CI: [-89.01, -57.85]ANCOVA
95% CI: [-54.29, -23.11]ANCOVA
Secondary
Total Pain Relief (TOTPAR)
Pain relief was measured using Categorical Pain Relief Rating Scale (0 = No relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief). Total pain relief scores (TOTPARs) were calculated by multiplying the pain relief score at each postdose time point by the duration (in hours) since the preceding time point and then summing these values.
Time frame: Up to 24 hours
Population: Per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen Sodium (Aleve, BAY117031) | Total Pain Relief (TOTPAR) | 47.16 Scores on a scale * hours | Standard Deviation 28.228 |
| Ibuprofen (Advil) | Total Pain Relief (TOTPAR) | 28.96 Scores on a scale * hours | Standard Deviation 21.097 |
| Placebo | Total Pain Relief (TOTPAR) | 13.40 Scores on a scale * hours | Standard Deviation 23.328 |
95% CI: [-23.52, -12.89]ANCOVA
95% CI: [-41.29, -26.14]ANCOVA
95% CI: [-23.09, -7.93]ANCOVA