Trial Outcomes & Findings for Study of Indomethacin Capsules to Treat Pain Following Bunionectomy (NCT NCT01626118)

NCT ID: NCT01626118

Last Updated: 2014-03-17

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". 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

373 participants

Primary outcome timeframe

0-48 hours

Results posted on

2014-03-17

Participant Flow

Participant milestones

Participant milestones
Measure
Indomethacin 40 mg TID
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
Placebo Group
Overall Study
STARTED
94
93
92
94
Overall Study
COMPLETED
92
91
90
91
Overall Study
NOT COMPLETED
2
2
2
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Indomethacin 40 mg TID
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
Placebo Group
Overall Study
Lack of Efficacy
1
0
1
3
Overall Study
Lost to Follow-up
1
0
0
0
Overall Study
Adverse Event
0
1
1
0
Overall Study
Investigator Decision
0
1
0
0

Baseline Characteristics

Study of Indomethacin Capsules to Treat Pain Following Bunionectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
Total
n=373 Participants
Total of all reporting groups
Age, Continuous
40.2 years
STANDARD_DEVIATION 12.27 • n=5 Participants
38.9 years
STANDARD_DEVIATION 12.5 • n=7 Participants
41.3 years
STANDARD_DEVIATION 12.57 • n=5 Participants
40.7 years
STANDARD_DEVIATION 11.32 • n=4 Participants
40.3 years
STANDARD_DEVIATION 12.16 • n=21 Participants
Sex: Female, Male
Female
80 Participants
n=5 Participants
77 Participants
n=7 Participants
77 Participants
n=5 Participants
83 Participants
n=4 Participants
317 Participants
n=21 Participants
Sex: Female, Male
Male
14 Participants
n=5 Participants
16 Participants
n=7 Participants
15 Participants
n=5 Participants
11 Participants
n=4 Participants
56 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
15 Participants
n=5 Participants
26 Participants
n=7 Participants
12 Participants
n=5 Participants
20 Participants
n=4 Participants
73 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
79 Participants
n=5 Participants
67 Participants
n=7 Participants
80 Participants
n=5 Participants
74 Participants
n=4 Participants
300 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
2 participants
n=5 Participants
2 participants
n=7 Participants
0 participants
n=5 Participants
1 participants
n=4 Participants
5 participants
n=21 Participants
Race/Ethnicity, Customized
Asian
2 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
2 participants
n=4 Participants
8 participants
n=21 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 participants
n=5 Participants
1 participants
n=7 Participants
2 participants
n=5 Participants
0 participants
n=4 Participants
3 participants
n=21 Participants
Race/Ethnicity, Customized
Black or African American
15 participants
n=5 Participants
25 participants
n=7 Participants
21 participants
n=5 Participants
19 participants
n=4 Participants
80 participants
n=21 Participants
Race/Ethnicity, Customized
White or Caucasian
77 participants
n=5 Participants
66 participants
n=7 Participants
69 participants
n=5 Participants
70 participants
n=4 Participants
282 participants
n=21 Participants
Race/Ethnicity, Customized
Other
0 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
2 participants
n=4 Participants
3 participants
n=21 Participants
Weight (kg)
73.81 KG
STANDARD_DEVIATION 14.686 • n=5 Participants
72.77 KG
STANDARD_DEVIATION 15.761 • n=7 Participants
74.99 KG
STANDARD_DEVIATION 17.821 • n=5 Participants
71.22 KG
STANDARD_DEVIATION 14.607 • n=4 Participants
73.19 KG
STANDARD_DEVIATION 15.758 • n=21 Participants
Height (cm)
166.28 CM
STANDARD_DEVIATION 8.059 • n=5 Participants
165.65 CM
STANDARD_DEVIATION 8.994 • n=7 Participants
166.52 CM
STANDARD_DEVIATION 9.761 • n=5 Participants
165.61 CM
STANDARD_DEVIATION 7.646 • n=4 Participants
166.01 CM
STANDARD_DEVIATION 8.621 • n=21 Participants
BMI (kg/m^2)
26.5 KG/M^2
STANDARD_DEVIATION 4.49 • n=5 Participants
26.3 KG/M^2
STANDARD_DEVIATION 4.34 • n=7 Participants
26.7 KG/M^2
STANDARD_DEVIATION 4.73 • n=5 Participants
25.8 KG/M^2
STANDARD_DEVIATION 4.57 • n=4 Participants
26.3 KG/M^2
STANDARD_DEVIATION 4.52 • n=21 Participants
Baseline pain intensity, mm
71.0 mm
STANDARD_DEVIATION 16.33 • n=5 Participants
71.2 mm
STANDARD_DEVIATION 16.11 • n=7 Participants
72.3 mm
STANDARD_DEVIATION 15.90 • n=5 Participants
73.9 mm
STANDARD_DEVIATION 16.6 • n=4 Participants
72.1 mm
STANDARD_DEVIATION 16.21 • n=21 Participants
Surgery duration, min
27.7 minutes
STANDARD_DEVIATION 7.45 • n=5 Participants
27.6 minutes
STANDARD_DEVIATION 7.95 • n=7 Participants
28.5 minutes
STANDARD_DEVIATION 8.63 • n=5 Participants
27.2 minutes
STANDARD_DEVIATION 6.59 • n=4 Participants
27.7 minutes
STANDARD_DEVIATION 7.67 • n=21 Participants

PRIMARY outcome

Timeframe: 0-48 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
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
623.162 mm*hour
Standard Deviation 1182.0912
342.779 mm*hour
Standard Deviation 858.6326
280.517 mm*hour
Standard Deviation 817.6026

SECONDARY outcome

Timeframe: 0-4 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
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
35.3 mm*hour
Standard Deviation 79.6
24.8 mm*hour
Standard Deviation 54.6
18.4 mm*hour
Standard Deviation 62.1

SECONDARY outcome

Timeframe: 0-8 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
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
75.5 mm*hour
Standard Deviation 152.5
47.6 mm*hour
Standard Deviation 109.9
35.8 mm*hour
Standard Deviation 107.9

SECONDARY outcome

Timeframe: 0-24 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
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
265.2 mm*hour
Standard Deviation 516.2
156.8 mm*hour
Standard Deviation 384.0
115.5 mm*hour
Standard Deviation 346.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
Total Pain Relief (TOTPAR) Over 0 to 4 Hours (TOTPAR-4).
2.6 units on a scale*hour
Standard Deviation 3.8
2.8 units on a scale*hour
Standard Deviation 3.8
2.0 units on a scale*hour
Standard Deviation 2.9
1.9 units on a scale*hour
Standard Deviation 3.1

SECONDARY outcome

Timeframe: 0-8 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
TOTPAR-8. Total Pain Relief (TOTPAR) Over 0 to 8 Hours
5.0 units on a scale*hour
Standard Deviation 8.0
5.4 units on a scale*hour
Standard Deviation 8.1
3.5 units on a scale*hour
Standard Deviation 5.9
3.0 units on a scale*hour
Standard Deviation 5.8

SECONDARY outcome

Timeframe: 0-24 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
TOTPAR-24. Total Pain Relief (TOTPAR) Over 0 to 24 Hours
16.2 units on a scale*hour
Standard Deviation 29.1
16.8 units on a scale*hour
Standard Deviation 28.0
10.1 units on a scale*hour
Standard Deviation 21.8
7.8 units on a scale*hour
Standard Deviation 19.1

SECONDARY outcome

Timeframe: 0-48 hours

Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug.

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.

Outcome measures

Outcome measures
Measure
Indomethacin 40 mg TID
n=94 Participants
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 Participants
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 Participants
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 Participants
Placebo Group
TOTPAR-48. Total Pain Relief (TOTPAR) Over 0 to 48 Hours
34.7 units on a scale*hour
Standard Deviation 65.1
37.0 units on a scale*hour
Standard Deviation 64.5
21.2 units on a scale*hour
Standard Deviation 49.3
17.3 units on a scale*hour
Standard Deviation 45.6

Adverse Events

Indomethacin 40 mg TID

Serious events: 0 serious events
Other events: 65 other events
Deaths: 0 deaths

Indomethacin 40 mg BID

Serious events: 0 serious events
Other events: 74 other events
Deaths: 0 deaths

Indomethacin 20 mg TID

Serious events: 0 serious events
Other events: 68 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 71 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Indomethacin 40 mg TID
n=94 participants at risk
Indomethacin Nanoformulation Capsules 40 mg TID
Indomethacin 40 mg BID
n=93 participants at risk
Indomethacin Nanoformulation Capsules 40 mg BID
Indomethacin 20 mg TID
n=92 participants at risk
Indomethacin Nanoformulation Capsules 20 mg TID
Placebo
n=94 participants at risk
Placebo Group
Gastrointestinal disorders
Nausea
34.0%
32/94
38.7%
36/93
37.0%
34/92
35.1%
33/94
Injury, poisoning and procedural complications
Postprocedural edema
21.3%
20/94
19.4%
18/93
27.2%
25/92
30.9%
29/94
Nervous system disorders
Dizziness
17.0%
16/94
12.9%
12/93
13.0%
12/92
17.0%
16/94
Nervous system disorders
Headache
18.1%
17/94
12.9%
12/93
9.8%
9/92
14.9%
14/94
Gastrointestinal disorders
Vomiting
9.6%
9/94
12.9%
12/93
12.0%
11/92
8.5%
8/94
Gastrointestinal disorders
Constipation
3.2%
3/94
7.5%
7/93
8.7%
8/92
5.3%
5/94
Injury, poisoning and procedural complications
Post procedural haemorrhage
4.3%
4/94
7.5%
7/93
3.3%
3/92
5.3%
5/94

Additional Information

Daniel Solorio

Iroko Pharmaceuticals, LLC

Phone: 267-546-3150

Results disclosure agreements

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