Trial Outcomes & Findings for Study of Indomethacin Capsules to Treat Pain Following Bunionectomy (NCT NCT01543685)

NCT ID: NCT01543685

Last Updated: 2014-02-04

Results Overview

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". 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 462 participants
• Primary outcome timeframe: 0 - 48 hours
• Results posted on: 2014-02-04

Participant Flow

Participant milestones

Measure	Indomethacin 40 mg TID Indomethacin : 40 mg TID capsules	Indomethacin 40 mg BID Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID Indomethacin : 20 mg TID capsules	Celecoxib 200 mg Celecoxib : 200 mg capsules	Placebo Placebo : Capsules
Overall Study STARTED	93	91	91	93	94
Overall Study COMPLETED	90	88	89	93	90
Overall Study NOT COMPLETED	3	3	2	0	4

Reasons for withdrawal

Measure	Indomethacin 40 mg TID Indomethacin : 40 mg TID capsules	Indomethacin 40 mg BID Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID Indomethacin : 20 mg TID capsules	Celecoxib 200 mg Celecoxib : 200 mg capsules	Placebo Placebo : Capsules
Overall Study Lack of Efficacy	1	2	2	0	2
Overall Study Adverse Event	2	1	0	0	2

Baseline Characteristics

Study of Indomethacin Capsules to Treat Pain Following Bunionectomy

Baseline characteristics by cohort

Measure	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules	Placebo n=94 Participants Placebo : Capsules	Total n=462 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 12.3 • n=5 Participants	41.5 years STANDARD_DEVIATION 13.4 • n=7 Participants	41.4 years STANDARD_DEVIATION 12.4 • n=5 Participants	41.5 years STANDARD_DEVIATION 11.4 • n=4 Participants	40.4 years STANDARD_DEVIATION 13.3 • n=21 Participants	41.2 years STANDARD_DEVIATION 12.5 • n=8 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	79 Participants n=7 Participants	72 Participants n=5 Participants	79 Participants n=4 Participants	77 Participants n=21 Participants	384 Participants n=8 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants	14 Participants n=4 Participants	17 Participants n=21 Participants	78 Participants n=8 Participants
Region of Enrollment United States	93 participants n=5 Participants	91 participants n=7 Participants	91 participants n=5 Participants	93 participants n=4 Participants	94 participants n=21 Participants	462 participants n=8 Participants

PRIMARY outcome

Timeframe: 0 - 48 hours

Population: Intent to Treat Population

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".

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.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
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)	329.8 mm*hour Standard Deviation 903.3	377.3 mm*hour Standard Deviation 1045.1	280.5 mm*hour Standard Deviation 799.8	69.4 mm*hour Standard Deviation 364.3	508.2 mm*hour Standard Deviation 1125.6

SECONDARY outcome

Timeframe: 0 - 4 hours

Population: Intent to Treat Population

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".

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.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
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.	29.8 mm*hour Standard Deviation 70.8	17.9 mm*hour Standard Deviation 57.1	20.4 mm*hour Standard Deviation 54.6	8.9 mm*hour Standard Deviation 38.3	30.7 mm*hour Standard Deviation 74.9

SECONDARY outcome

Timeframe: 0 - 8 hours

Population: Intent to Treat Population

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".

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.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
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.	55.4 mm*hour Standard Deviation 132.4	45.7 mm*hour Standard Deviation 122.7	37.2 mm*hour Standard Deviation 97.4	12.0 mm*hour Standard Deviation 49.9	64.1 mm*hour Standard Deviation 144.6

SECONDARY outcome

Timeframe: 0 - 24 hours

Population: Intent to Treat Population

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".

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.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
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	158.3 mm*hour Standard Deviation 405.2	176.9 mm*hour Standard Deviation 469.6	119.4 mm*hour Standard Deviation 329.6	28.3 mm*hour Standard Deviation 132.1	226.9 mm*hour Standard Deviation 500.9

SECONDARY outcome

Timeframe: 0 - 4 hours

Population: Intent to Treat Population

Pain relief was assessed using a 5-point categorical scale at all assessment time points 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.

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. In this way individual scores covering a longer time period were given more weight. The minimum theoretical score is 0 units, which represent no relief from pain (score of 0 on categorical scale) at all time points after time 0. The maximum theoretical score is 16 units, which represents complete relief from pain (score of 4 on a categorical scale) at all time points after time 0.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4).	2.1 units on a scale*hour Standard Deviation 3.4	1.7 units on a scale*hour Standard Deviation 2.9	1.8 units on a scale*hour Standard Deviation 2.8	1.2 units on a scale*hour Standard Deviation 2.1	2.5 units on a scale*hour Standard Deviation 3.6

SECONDARY outcome

Timeframe: 0 - 8 hours

Population: Intent to Treat Population

Pain relief was assessed using a 5-point categorical scale at all assessment time points 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.

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. In this way individual scores covering a longer time period were given more weight. The minimum theoretical score is 0 units, which represent no relief from pain (score of 0 on categorical scale) at all time points after time 0. The maximum theoretical score is 32 units, which represents complete relief from pain (score of 4 on a categorical scale) at all time points after time 0.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours	3.4 units on a scale*hour Standard Deviation 6.3	3.4 units on a scale*hour Standard Deviation 6.3	3.0 units on a scale*hour Standard Deviation 5.6	1.5 units on a scale*hour Standard Deviation 2.9	4.5 units on a scale*hour Standard Deviation 7.4

SECONDARY outcome

Timeframe: 0 - 24 hours

Population: Intent to Treat Population

Pain relief was assessed using a 5-point categorical scale at all assessment time points 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.

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. In this way individual scores covering a longer time period were given more weight. The minimum theoretical score is 0 units, which represent no relief from pain (score of 0 on categorical scale) at all time points after time 0. The maximum theoretical score is 96 units, which represents complete relief from pain (score of 4 on a categorical scale) at all time points after time 0.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours	8.9 units on a scale*hour Standard Deviation 20.4	10.0 units on a scale*hour Standard Deviation 23.0	7.7 units on a scale*hour Standard Deviation 18.1	2.6 units on a scale*hour Standard Deviation 8.8	13.4 units on a scale*hour Standard Deviation 26.4

SECONDARY outcome

Timeframe: 0 - 48 hours

Population: Intent to Treat Population

Pain relief was assessed using a 5-point categorical scale at all assessment time points 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.

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. In this way individual scores covering a longer time period were given more weight. The minimum theoretical score is 0 units, which represent no relief from pain (score of 0 on categorical scale) at all time points after time 0. The maximum theoretical score is 192 units, which represents complete relief from pain (score of 4 on a categorical scale) at all time points after time 0.

Outcome measures

Measure	Indomethacin 40 mg BID n=91 Participants Indomethacin : 40 mg BID capsules	Indomethacin 20 mg TID n=91 Participants Indomethacin : 20 mg TID capsules	Celecoxib 200 mg n=93 Participants Celecoxib : 200 mg capsules	Placebo n=94 Participants Placebo : Capsules	Indomethacin 40 mg TID n=93 Participants Indomethacin : 40 mg TID capsules
TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours	17.8 units on a scale*hour Standard Deviation 45.6	19.6 units on a scale*hour Standard Deviation 49.3	16.4 units on a scale*hour Standard Deviation 43.2	5.2 units on a scale*hour Standard Deviation 22.9	29.3 units on a scale*hour Standard Deviation 59.8

Adverse Events

Celecoxib 200 mg

Serious events: 0 serious events

Other events: 68 other events

Deaths: 0 deaths

Indomethacin 20 mg TID

Serious events: 0 serious events

Other events: 69 other events

Deaths: 0 deaths

Indomethacin 40 mg BID

Serious events: 1 serious events

Other events: 74 other events

Deaths: 0 deaths

Indomethacin 40 mg TID

Serious events: 0 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Measure	Celecoxib 200 mg n=93 participants at risk Celecoxib : 200 mg capsules	Indomethacin 20 mg TID n=91 participants at risk Indomethacin : 20 mg TID capsules	Indomethacin 40 mg BID n=91 participants at risk Indomethacin : 40 mg BID capsules	Indomethacin 40 mg TID n=93 participants at risk Indomethacin : 40 mg TID capsules	Placebo n=94 participants at risk Placebo : Capsules
Vascular disorders Deep vein thrombosis	0.00% 0/93	0.00% 0/91	1.1% 1/91	0.00% 0/93	0.00% 0/94

Other adverse events

Measure	Celecoxib 200 mg n=93 participants at risk Celecoxib : 200 mg capsules	Indomethacin 20 mg TID n=91 participants at risk Indomethacin : 20 mg TID capsules	Indomethacin 40 mg BID n=91 participants at risk Indomethacin : 40 mg BID capsules	Indomethacin 40 mg TID n=93 participants at risk Indomethacin : 40 mg TID capsules	Placebo n=94 participants at risk Placebo : Capsules
Gastrointestinal disorders Nausea	32.3% 30/93	31.9% 29/91	26.4% 24/91	32.3% 30/93	36.2% 34/94
Nervous system disorders Dizziness	7.5% 7/93	6.6% 6/91	15.4% 14/91	12.9% 12/93	17.0% 16/94
Gastrointestinal disorders Vomiting	3.2% 3/93	11.0% 10/91	7.7% 7/91	5.4% 5/93	13.8% 13/94
Injury, poisoning and procedural complications Post procedural edema	26.9% 25/93	25.3% 23/91	24.2% 22/91	25.8% 24/93	33.0% 31/94
Nervous system disorders Headache	5.4% 5/93	12.1% 11/91	14.3% 13/91	12.9% 12/93	7.4% 7/94
Injury, poisoning and procedural complications Post procedural hemorrhage	8.6% 8/93	6.6% 6/91	14.3% 13/91	5.4% 5/93	6.4% 6/94
Skin and subcutaneous tissue disorders Erythema	1.1% 1/93	2.2% 2/91	2.2% 2/91	2.2% 2/93	6.4% 6/94
Skin and subcutaneous tissue disorders Pruritus	4.3% 4/93	5.5% 5/91	1.1% 1/91	3.2% 3/93	0.00% 0/94
Nervous system disorders Presyncope	2.2% 2/93	1.1% 1/91	5.5% 5/91	1.1% 1/93	2.1% 2/94

Additional Information

Daniel Solorio

Iroko Pharmaceuticals, LLC

Phone: 267-546-3150

Email: dsolorio@iroko.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place