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Co-crystal E-58425 vs Tramadol and Celecoxib for Moderate to Severe Acute Pain After Bunionectomy. Phase III Clinical Trial.

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ClinicalTrials.gov Identifier: NCT03108482
Recruitment Status : Completed
First Posted : April 11, 2017
Results First Posted : January 9, 2019
Last Update Posted : January 24, 2019
Sponsor:
Collaborator:
Premier Research Group plc
Information provided by (Responsible Party):
Laboratorios del Dr. Esteve, S.A.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Acute Post-surgical Pain
Interventions Drug: Co-crystal E-58425 (Tramadol/Celecoxib)
Drug: Tramadol (Ultram®)
Drug: Celecoxib (Celebrex®)
Drug: Placebo
Enrollment 637
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Hide Arm/Group Description

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: 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: 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: 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.

Period Title: Overall Study
Started [1] 183 183 182 89
Completed 183 179 180 86
Not Completed 0 4 2 3
[1]
Safety Analysis Set (Study Treatments as actually received)
Arm/Group Title Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo Total
Hide Arm/Group Description

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: 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: 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: 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 of all reporting groups
Overall Number of Baseline Participants 183 183 182 89 637
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 183 participants 183 participants 182 participants 89 participants 637 participants
43.9  (14.5) 48.1  (14.4) 45.1  (13.0) 46.1  (14.9) 45.8  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants 183 participants 182 participants 89 participants 637 participants
Female
161
  88.0%
150
  82.0%
161
  88.5%
75
  84.3%
547
  85.9%
Male
22
  12.0%
33
  18.0%
21
  11.5%
14
  15.7%
90
  14.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants 183 participants 182 participants 89 participants 637 participants
Hispanic or Latino
50
  27.3%
45
  24.6%
38
  20.9%
18
  20.2%
151
  23.7%
Not Hispanic or Latino
133
  72.7%
138
  75.4%
144
  79.1%
71
  79.8%
486
  76.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 183 participants 183 participants 182 participants 89 participants 637 participants
183 183 182 89 637
1.Primary Outcome
Title Sum of Pain Intensity Differences (SPID)
Hide Description 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.
Time Frame Assessments was recorded from time 0 to 48 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (Study Treatments as randomized)
Arm/Group Title Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Hide Arm/Group Description:

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: 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: 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: 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 Number of Participants Analyzed 184 183 181 89
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-139.12
(-151.75 to -126.49)
-109.08
(-121.74 to -96.42)
-103.69
(-116.39 to -90.99)
-74.55
(-92.48 to -56.61)
Time Frame 10 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Hide Arm/Group Description

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: 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: 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: 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.

All-Cause Mortality
Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/183 (0.00%)   0/183 (0.00%)   0/182 (0.00%)   0/89 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/183 (0.00%)   0/183 (0.00%)   0/182 (0.00%)   0/89 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Co-crystal E-58425 (Tramadol/Celecoxib) Tramadol (Ultram®) Celecoxib (Celebrex®) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   87/183 (47.54%)   101/183 (55.19%)   60/182 (32.97%)   31/89 (34.83%) 
Gastrointestinal disorders         
Constipation *  4/183 (2.19%)  13/183 (7.10%)  9/182 (4.95%)  3/89 (3.37%) 
Dry mouth *  0/183 (0.00%)  6/183 (3.28%)  5/182 (2.75%)  0/89 (0.00%) 
Nausea *  55/183 (30.05%)  69/183 (37.70%)  30/182 (16.48%)  17/89 (19.10%) 
Vomiting *  29/183 (15.85%)  30/183 (16.39%)  4/182 (2.20%)  2/89 (2.25%) 
General disorders         
Asthenia *  1/183 (0.55%)  4/183 (2.19%)  0/182 (0.00%)  0/89 (0.00%) 
Metabolism and nutrition disorders         
Decreased Appetite *  6/183 (3.28%)  11/183 (6.01%)  1/182 (0.55%)  0/89 (0.00%) 
Nervous system disorders         
Dizziness *  31/183 (16.94%)  34/183 (18.58%)  9/182 (4.95%)  13/89 (14.61%) 
Headache *  21/183 (11.48%)  33/183 (18.03%)  20/182 (10.99%)  6/89 (6.74%) 
Somnolence *  15/183 (8.20%)  10/183 (5.46%)  4/182 (2.20%)  3/89 (3.37%) 
Skin and subcutaneous tissue disorders         
Pruritus *  7/183 (3.83%)  4/183 (2.19%)  3/182 (1.65%)  0/89 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Neus Gascon
Organization: Esteve Pharmaceuticals, S.A.
Phone: +34934446000
EMail: ngascon@esteve.com
Layout table for additonal information
Responsible Party: Laboratorios del Dr. Esteve, S.A.
ClinicalTrials.gov Identifier: NCT03108482     History of Changes
Other Study ID Numbers: ESTEVE-SUSA-301
First Submitted: March 30, 2017
First Posted: April 11, 2017
Results First Submitted: November 8, 2018
Results First Posted: January 9, 2019
Last Update Posted: January 24, 2019