Other Acute Postoperative Pain
Conditions
Brief summary
The purpose of this study is to determine whether Indomethacin \[Test\] Capsules are safe and effective for the treatment of postoperative bunionectomy pain.
Interventions
DRUGIndomethacin
capsules, 40 mg, TID
DRUGPlacebo
capsules
Sponsors
Iroko Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient is male or female between 18 and 65 years of age * For women of child-bearing potential: a woman who is not pregnant and not nursing, and who is practicing an acceptable method of birth control * Has undergone primary, unilateral, first metatarsal bunionectomy with no additional collateral procedures * Patient must be willing to stay at the study site ≥ 72 hours
Exclusion criteria
* Patient has hypersensitivity, allergy, or clinically significant intolerance to any medications to be used in the study, or related drugs * Patient has a current disease or history of a disease that will impact the study or the patient's well-being * Patient has used or intends to use any of the medications that are prohibited by the protocol * Patient has a history of drug or alcohol abuse or dependence, or patient has a positive urine drug screen or alcohol breathalyzer test * Patient has taken another investigational drug within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48) | 0-48 hours | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40, and 48 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry. | 0-8 hours | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment. |
| VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry. | 0-24 hours | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 hours. The VAS summed pain intensity difference (VASSPID) is calculated as a time-weighted sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment. |
| Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4). | 0-4 hours | Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3 & 4 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 16 units, which represents complete pain relief (4 on scale) at all points after 0. |
| VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry. | 0-4 hours | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, and 4 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment. |
| TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours | 0-24 hours | Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, & 24 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 96 units, which represents complete pain relief (4 on scale) at all points after 0. |
| TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours | 0-48 hours | Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40 & 48 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 192 units, which represents complete pain relief (4 on scale) at all points after 0. |
| TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours | 0-8 hours | Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7 & 8 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 32 units, which represents complete pain relief (4 on scale) at all points after 0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indomethacin 40 mg TID Indomethacin Nanoformulation Capsules 40 mg TID | 94 |
| Indomethacin 40 mg BID Indomethacin Nanoformulation Capsules 40 mg BID | 93 |
| Indomethacin 20 mg TID Indomethacin Nanoformulation Capsules 20 mg TID | 92 |
| Placebo Placebo Group | 94 |
| Total | 373 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 |
| Overall Study | Investigator Decision | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Indomethacin 40 mg BID | Total | Placebo | Indomethacin 40 mg TID | Indomethacin 20 mg TID |
|---|---|---|---|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 12.5 | 40.3 years STANDARD_DEVIATION 12.16 | 40.7 years STANDARD_DEVIATION 11.32 | 40.2 years STANDARD_DEVIATION 12.27 | 41.3 years STANDARD_DEVIATION 12.57 |
| Baseline pain intensity, mm | 71.2 mm STANDARD_DEVIATION 16.11 | 72.1 mm STANDARD_DEVIATION 16.21 | 73.9 mm STANDARD_DEVIATION 16.6 | 71.0 mm STANDARD_DEVIATION 16.33 | 72.3 mm STANDARD_DEVIATION 15.9 |
| BMI (kg/m^2) | 26.3 KG/M^2 STANDARD_DEVIATION 4.34 | 26.3 KG/M^2 STANDARD_DEVIATION 4.52 | 25.8 KG/M^2 STANDARD_DEVIATION 4.57 | 26.5 KG/M^2 STANDARD_DEVIATION 4.49 | 26.7 KG/M^2 STANDARD_DEVIATION 4.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 73 Participants | 20 Participants | 15 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 300 Participants | 74 Participants | 79 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 165.65 CM STANDARD_DEVIATION 8.994 | 166.01 CM STANDARD_DEVIATION 8.621 | 165.61 CM STANDARD_DEVIATION 7.646 | 166.28 CM STANDARD_DEVIATION 8.059 | 166.52 CM STANDARD_DEVIATION 9.761 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants | 5 participants | 1 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 8 participants | 2 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 25 participants | 80 participants | 19 participants | 15 participants | 21 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 3 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Other | 0 participants | 3 participants | 2 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White or Caucasian | 66 participants | 282 participants | 70 participants | 77 participants | 69 participants |
| Sex: Female, Male Female | 77 Participants | 317 Participants | 83 Participants | 80 Participants | 77 Participants |
| Sex: Female, Male Male | 16 Participants | 56 Participants | 11 Participants | 14 Participants | 15 Participants |
| Surgery duration, min | 27.6 minutes STANDARD_DEVIATION 7.95 | 27.7 minutes STANDARD_DEVIATION 7.67 | 27.2 minutes STANDARD_DEVIATION 6.59 | 27.7 minutes STANDARD_DEVIATION 7.45 | 28.5 minutes STANDARD_DEVIATION 8.63 |
| Weight (kg) | 72.77 KG STANDARD_DEVIATION 15.761 | 73.19 KG STANDARD_DEVIATION 15.758 | 71.22 KG STANDARD_DEVIATION 14.607 | 73.81 KG STANDARD_DEVIATION 14.686 | 74.99 KG STANDARD_DEVIATION 17.821 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 65 / 94 | 74 / 93 | 68 / 92 | 71 / 94 |
| serious Total, serious adverse events | 0 / 94 | 0 / 93 | 0 / 92 | 0 / 94 |
Outcome results
Primary
The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48)
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40, and 48 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment.
Time frame: 0-48 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48) | 598.670 mm*hour | Standard Deviation 1173.7863 |
| Indomethacin 40 mg BID | The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48) | 623.162 mm*hour | Standard Deviation 1182.0912 |
| Indomethacin 20 mg TID | The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48) | 342.779 mm*hour | Standard Deviation 858.6326 |
| Placebo | The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale From 0 to 48 Hours After Trial Entry (VASSPID-48) | 280.517 mm*hour | Standard Deviation 817.6026 |
Comparison: The p value was obtained from an analysis of covariance (ANCOVA) model that included treatment effect as the factor and baseline pain intensity as the covariate. This was the primary analysis of the primary efficacy parameter.p-value: 0.03495% CI: [23.297, 611.926]ANCOVA
Comparison: The p value was obtained from an analysis of covariance (ANCOVA) model that included treatment effect as the factor and baseline pain intensity as the covariate. This was the primary analysis of the primary efficacy parameter.p-value: 0.02395% CI: [47.09, 637.175]ANCOVA
Comparison: The p value was obtained from an analysis of covariance (ANCOVA) model that included treatment effect as the factor and baseline pain intensity as the covariate. This was the primary analysis of the primary efficacy parameter.p-value: 0.6895% CI: [-233.527, 357.471]ANCOVA
Comparison: The p value was obtained from a mixed-model repeated-measure (MMRM) model that used all available data from all subjects to derive an estimate of pain intensity scores for subjects following study withdrawal, rather than imputing a score for individual subjects. The MMRM analysis was a sensitivity analysis of the primary efficacy parameter.p-value: <0.00195% CI: [301.93, 704.086]Mixed Models Analysis
Comparison: The p value was obtained from a mixed-model repeated-measure (MMRM) model that used all available data from all subjects to derive an estimate of pain intensity scores for subjects following study withdrawal, rather than imputing a score for individual subjects. The MMRM analysis was a sensitivity analysis of the primary efficacy parameter.p-value: <0.00195% CI: [309.749, 712.965]Mixed Models Analysis
Comparison: The p value was obtained from a mixed-model repeated-measure (MMRM) model that used all available data from all subjects to derive an estimate of pain intensity scores for subjects following study withdrawal, rather than imputing a score for individual subjects. The MMRM analysis was a sensitivity analysis of the primary efficacy parameter.p-value: <0.00195% CI: [139.249, 543.215]Mixed Models Analysis
Secondary
Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4).
Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3 & 4 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 16 units, which represents complete pain relief (4 on scale) at all points after 0.
Time frame: 0-4 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4). | 2.6 units on a scale*hour | Standard Deviation 3.8 |
| Indomethacin 40 mg BID | Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4). | 2.8 units on a scale*hour | Standard Deviation 3.8 |
| Indomethacin 20 mg TID | Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4). | 2.0 units on a scale*hour | Standard Deviation 2.9 |
| Placebo | Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4). | 1.9 units on a scale*hour | Standard Deviation 3.1 |
p-value: 0.141t-test, 2 sided
p-value: 0.071t-test, 2 sided
p-value: 0.716t-test, 2 sided
Secondary
TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours
Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, & 24 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 96 units, which represents complete pain relief (4 on scale) at all points after 0.
Time frame: 0-24 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours | 16.2 units on a scale*hour | Standard Deviation 29.1 |
| Indomethacin 40 mg BID | TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours | 16.8 units on a scale*hour | Standard Deviation 28 |
| Indomethacin 20 mg TID | TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours | 10.1 units on a scale*hour | Standard Deviation 21.8 |
| Placebo | TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours | 7.8 units on a scale*hour | Standard Deviation 19.1 |
p-value: 0.021t-test, 2 sided
p-value: 0.012t-test, 2 sided
p-value: 0.447t-test, 2 sided
Secondary
TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours
Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40 & 48 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 192 units, which represents complete pain relief (4 on scale) at all points after 0.
Time frame: 0-48 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours | 34.7 units on a scale*hour | Standard Deviation 65.1 |
| Indomethacin 40 mg BID | TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours | 37.0 units on a scale*hour | Standard Deviation 64.5 |
| Indomethacin 20 mg TID | TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours | 21.2 units on a scale*hour | Standard Deviation 49.3 |
| Placebo | TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours | 17.3 units on a scale*hour | Standard Deviation 45.6 |
p-value: 0.036t-test, 2 sided
p-value: 0.017t-test, 2 sided
p-value: 0.577t-test, 2 sided
Secondary
TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours
Pain relief was assessed with a 5-point categorical scale at all assessment timepoints after time 0. Subjects were asked How much relief have you had since your starting pain? with response choices of none=0, a little=1, some=2, a lot=3 and complete=4. Pain relief is assessed at the following points after time 0: 15, 30 & 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7 & 8 hours. The Total Pain Relief (TOTPAR) score for a given time interval is calculated as the sum of the pain relief scores at each follow-up time point (as recorded on the categorical pain relief scale) over that interval multiplied by the amount of time (in hours) since the prior assessment. Thus, individual scores covering a longer period were given more weight. The minimum theoretical score is 0 units, which represents no pain relief (0 on scale) at all points after time 0. The maximum theoretical score is 32 units, which represents complete pain relief (4 on scale) at all points after 0.
Time frame: 0-8 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours | 5.0 units on a scale*hour | Standard Deviation 8 |
| Indomethacin 40 mg BID | TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours | 5.4 units on a scale*hour | Standard Deviation 8.1 |
| Indomethacin 20 mg TID | TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours | 3.5 units on a scale*hour | Standard Deviation 5.9 |
| Placebo | TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours | 3.0 units on a scale*hour | Standard Deviation 5.8 |
p-value: 0.049t-test, 2 sided
p-value: 0.02t-test, 2 sided
p-value: 0.593t-test, 2 sided
Secondary
VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry.
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 hours. The VAS summed pain intensity difference (VASSPID) is calculated as a time-weighted sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment.
Time frame: 0-24 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry. | 268.4 mm*hour | Standard Deviation 526.9 |
| Indomethacin 40 mg BID | VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry. | 265.2 mm*hour | Standard Deviation 516.2 |
| Indomethacin 20 mg TID | VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry. | 156.8 mm*hour | Standard Deviation 384 |
| Placebo | VASSPID-24. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 24 Hours After Trial Entry. | 115.5 mm*hour | Standard Deviation 346.5 |
p-value: 0.02t-test, 2 sided
p-value: 0.021t-test, 2 sided
p-value: 0.441t-test, 2 sided
Secondary
VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry.
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, and 4 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment.
Time frame: 0-4 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry. | 31.5 mm*hour | Standard Deviation 74.4 |
| Indomethacin 40 mg BID | VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry. | 35.3 mm*hour | Standard Deviation 79.6 |
| Indomethacin 20 mg TID | VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry. | 24.8 mm*hour | Standard Deviation 54.6 |
| Placebo | VASSPID-4. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 4 Hours After Trial Entry. | 18.4 mm*hour | Standard Deviation 62.1 |
p-value: 0.191t-test, 2 sided
p-value: 0.108t-test, 2 sided
p-value: 0.461t-test, 2 sided
Secondary
VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry.
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Possible Pain. Pain intensity is assessed at baseline (time 0) and at the following time points after time 0: 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours. The VAS summed pain intensity difference (VASSPID) is calculated as the sum of the pain intensity difference values at each follow-up time point (difference between the starting pain intensity and the pain intensity at the given assessment time) multiplied by the amount of time (in hours) since the prior assessment.
Time frame: 0-8 hours
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin 40 mg TID | VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry. | 69.7 mm*hour | Standard Deviation 151.7 |
| Indomethacin 40 mg BID | VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry. | 75.5 mm*hour | Standard Deviation 152.5 |
| Indomethacin 20 mg TID | VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry. | 47.6 mm*hour | Standard Deviation 109.9 |
| Placebo | VASSPID-8. The Time-Weighted Summed Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale (VASSPID) From 0 to 8 Hours After Trial Entry. | 35.8 mm*hour | Standard Deviation 107.9 |
p-value: 0.041t-test, 2 sided
p-value: 0.079t-test, 2 sided
p-value: 0.458t-test, 2 sided