Trial Outcomes & Findings for Co-crystal E-58425 vs Tramadol and Celecoxib for Moderate to Severe Acute Pain After Bunionectomy. Phase III Clinical Trial. (NCT NCT03108482)
NCT ID: NCT03108482
Last Updated: 2019-01-24
Results Overview
The primary efficacy variable was the Pain Intensity (PI) measured by the Numerical Pain Rating Scale (NPRS); a scale from zero to 10 on which subjects circled a single number to indicate current pain level, with zero representing "No Pain" and 10 representing "Worst Possible Pain". The primary analysis endpoint was the Sum of Pain Intensity Differences (SPID) from 0 to 48 hours. Pain Intensity Differences (PID) was the difference between current PI at assessment minus baseline PI (prior to the first dose). Baseline PI ranged from 5 to 9. SPID was calculated as a time-weighted Sum of PID scores over 48 hours. Negative differences correspond to an amelioration of pain, while positive differences correspond to recrudescence of pain. The total scale ranged from -480 (best) to +480 (worst). A higher negative value of SPID indicates greater pain relief.
COMPLETED
PHASE3
637 participants
Assessments was recorded from time 0 to 48 hours.
2019-01-24
Participant Flow
Participant milestones
| Measure |
Co-crystal E-58425 (Tramadol/Celecoxib)
Co-crystal E-58425 (Tramadol/Celecoxib): Two tablets of 100 mg every 12 hours. The total daily dose was 400 mg of Co-crystal E-58425.
Co-crystal E-58425 (Tramadol/Celecoxib): Co-crystal E-58425 (Tramadol/Celecoxib): Two immediate release oral over-encapsulated tablets of 100 mg, every 12 hours for 48 hours.
|
Tramadol (Ultram®)
Tramadol: One tablet of 50 mg every 6 hours. The total daily dose was 200 mg of tramadol.
Tramadol (Ultram®): Tramadol: One immediate release oral over-encapsulated tablet of 50 mg, every 6 hours for 48 hours.
|
Celecoxib (Celebrex®)
Celecoxib: One capsule of 100 mg every 12 hours. The total daily dose was 200 mg of celecoxib.
Celecoxib (Celebrex®): Celecoxib: One immediate release oral over-encapsulated capsule of 100 mg, every 12 hours for 48 hours.
|
Placebo
Placebo: One or two tablets of 100 mg every 6 hours.
Placebo: Placebo 100 mg or 200 mg oral over-encapsulated tablets every 6 hours for 48 hours.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
183
|
183
|
182
|
89
|
|
Overall Study
COMPLETED
|
183
|
179
|
180
|
86
|
|
Overall Study
NOT COMPLETED
|
0
|
4
|
2
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Co-crystal E-58425 vs Tramadol and Celecoxib for Moderate to Severe Acute Pain After Bunionectomy. Phase III Clinical Trial.
Baseline characteristics by cohort
| Measure |
Co-crystal E-58425 (Tramadol/Celecoxib)
n=183 Participants
Co-crystal E-58425 (Tramadol/Celecoxib): Two tablets of 100 mg every 12 hours. The total daily dose was 400 mg of Co-crystal E-58425.
Co-crystal E-58425 (Tramadol/Celecoxib): Co-crystal E-58425 (Tramadol/Celecoxib): Two immediate release oral over-encapsulated tablets of 100 mg, every 12 hours for 48 hours.
|
Tramadol (Ultram®)
n=183 Participants
Tramadol: One tablet of 50 mg every 6 hours. The total daily dose was 200 mg of tramadol.
Tramadol (Ultram®): Tramadol: One immediate release oral over-encapsulated tablet of 50 mg, every 6 hours for 48 hours.
|
Celecoxib (Celebrex®)
n=182 Participants
Celecoxib: One capsule of 100 mg every 12 hours. The total daily dose was 200 mg of celecoxib.
Celecoxib (Celebrex®): Celecoxib: One immediate release oral over-encapsulated capsule of 100 mg, every 12 hours for 48 hours.
|
Placebo
n=89 Participants
Placebo: One or two tablets of 100 mg every 6 hours.
Placebo: Placebo 100 mg or 200 mg oral over-encapsulated tablets every 6 hours for 48 hours.
|
Total
n=637 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
43.9 years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
48.1 years
STANDARD_DEVIATION 14.4 • n=7 Participants
|
45.1 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
46.1 years
STANDARD_DEVIATION 14.9 • n=4 Participants
|
45.8 years
STANDARD_DEVIATION 14.1 • n=21 Participants
|
|
Sex: Female, Male
Female
|
161 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
547 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
90 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
50 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
151 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
133 Participants
n=5 Participants
|
138 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
71 Participants
n=4 Participants
|
486 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
|
|
Region of Enrollment
United States
|
183 participants
n=5 Participants
|
183 participants
n=7 Participants
|
182 participants
n=5 Participants
|
89 participants
n=4 Participants
|
637 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Assessments was recorded from time 0 to 48 hours.Population: Full Analysis Set (Study Treatments as randomized)
The primary efficacy variable was the Pain Intensity (PI) measured by the Numerical Pain Rating Scale (NPRS); a scale from zero to 10 on which subjects circled a single number to indicate current pain level, with zero representing "No Pain" and 10 representing "Worst Possible Pain". The primary analysis endpoint was the Sum of Pain Intensity Differences (SPID) from 0 to 48 hours. Pain Intensity Differences (PID) was the difference between current PI at assessment minus baseline PI (prior to the first dose). Baseline PI ranged from 5 to 9. SPID was calculated as a time-weighted Sum of PID scores over 48 hours. Negative differences correspond to an amelioration of pain, while positive differences correspond to recrudescence of pain. The total scale ranged from -480 (best) to +480 (worst). A higher negative value of SPID indicates greater pain relief.
Outcome measures
| Measure |
Co-crystal E-58425 (Tramadol/Celecoxib)
n=184 Participants
Co-crystal E-58425 (Tramadol/Celecoxib): Two tablets of 100 mg every 12 hours. The total daily dose was 400 mg of Co-crystal E-58425.
Co-crystal E-58425 (Tramadol/Celecoxib): Co-crystal E-58425 (Tramadol/Celecoxib): Two immediate release oral over-encapsulated tablets of 100 mg, every 12 hours for 48 hours.
|
Tramadol (Ultram®)
n=183 Participants
Tramadol: One tablet of 50 mg every 6 hours. The total daily dose was 200 mg of tramadol.
Tramadol (Ultram®): Tramadol: One immediate release oral over-encapsulated tablet of 50 mg, every 6 hours for 48 hours.
|
Celecoxib (Celebrex®)
n=181 Participants
Celecoxib: One capsule of 100 mg every 12 hours. The total daily dose was 200 mg of celecoxib.
Celecoxib (Celebrex®): Celecoxib: One immediate release oral over-encapsulated capsule of 100 mg, every 12 hours for 48 hours.
|
Placebo
n=89 Participants
Placebo: One or two tablets of 100 mg every 6 hours.
Placebo: Placebo 100 mg or 200 mg oral over-encapsulated tablets every 6 hours for 48 hours.
|
|---|---|---|---|---|
|
Sum of Pain Intensity Differences (SPID)
|
-139.12 units on a scale
Interval -151.75 to -126.49
|
-109.08 units on a scale
Interval -121.74 to -96.42
|
-103.69 units on a scale
Interval -116.39 to -90.99
|
-74.55 units on a scale
Interval -92.48 to -56.61
|
Adverse Events
Co-crystal E-58425 (Tramadol/Celecoxib)
Tramadol (Ultram®)
Celecoxib (Celebrex®)
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Co-crystal E-58425 (Tramadol/Celecoxib)
n=183 participants at risk
Co-crystal E-58425 (Tramadol/Celecoxib): Two tablets of 100 mg every 12 hours. The total daily dose was 400 mg of Co-crystal E-58425.
Co-crystal E-58425 (Tramadol/Celecoxib): Co-crystal E-58425 (Tramadol/Celecoxib): Two immediate release oral over-encapsulated tablets of 100 mg, every 12 hours for 48 hours.
|
Tramadol (Ultram®)
n=183 participants at risk
Tramadol: One tablet of 50 mg every 6 hours. The total daily dose was 200 mg of tramadol.
Tramadol (Ultram®): Tramadol: One immediate release oral over-encapsulated tablet of 50 mg, every 6 hours for 48 hours.
|
Celecoxib (Celebrex®)
n=182 participants at risk
Celecoxib: One capsule of 100 mg every 12 hours. The total daily dose was 200 mg of celecoxib.
Celecoxib (Celebrex®): Celecoxib: One immediate release oral over-encapsulated capsule of 100 mg, every 12 hours for 48 hours.
|
Placebo
n=89 participants at risk
Placebo: One or two tablets of 100 mg every 6 hours.
Placebo: Placebo 100 mg or 200 mg oral over-encapsulated tablets every 6 hours for 48 hours.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
2.2%
4/183 • 10 days
|
7.1%
13/183 • 10 days
|
4.9%
9/182 • 10 days
|
3.4%
3/89 • 10 days
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/183 • 10 days
|
3.3%
6/183 • 10 days
|
2.7%
5/182 • 10 days
|
0.00%
0/89 • 10 days
|
|
Gastrointestinal disorders
Nausea
|
30.1%
55/183 • 10 days
|
37.7%
69/183 • 10 days
|
16.5%
30/182 • 10 days
|
19.1%
17/89 • 10 days
|
|
Gastrointestinal disorders
Vomiting
|
15.8%
29/183 • 10 days
|
16.4%
30/183 • 10 days
|
2.2%
4/182 • 10 days
|
2.2%
2/89 • 10 days
|
|
General disorders
Asthenia
|
0.55%
1/183 • 10 days
|
2.2%
4/183 • 10 days
|
0.00%
0/182 • 10 days
|
0.00%
0/89 • 10 days
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
3.3%
6/183 • 10 days
|
6.0%
11/183 • 10 days
|
0.55%
1/182 • 10 days
|
0.00%
0/89 • 10 days
|
|
Nervous system disorders
Dizziness
|
16.9%
31/183 • 10 days
|
18.6%
34/183 • 10 days
|
4.9%
9/182 • 10 days
|
14.6%
13/89 • 10 days
|
|
Nervous system disorders
Headache
|
11.5%
21/183 • 10 days
|
18.0%
33/183 • 10 days
|
11.0%
20/182 • 10 days
|
6.7%
6/89 • 10 days
|
|
Nervous system disorders
Somnolence
|
8.2%
15/183 • 10 days
|
5.5%
10/183 • 10 days
|
2.2%
4/182 • 10 days
|
3.4%
3/89 • 10 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.8%
7/183 • 10 days
|
2.2%
4/183 • 10 days
|
1.6%
3/182 • 10 days
|
0.00%
0/89 • 10 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
- Publication restrictions are in place
Restriction type: OTHER