A Two-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol HCl Once-a-Day Versus Placebo for the Treatment of Pain Due to Osteoarthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Labopharm Inc.
ClinicalTrials.gov Identifier:
NCT00833794
First received: January 29, 2009
Last updated: April 25, 2012
Last verified: April 2012
Results First Received: April 9, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Pain
Osteoarthritis
Interventions: Drug: Tramadol Once a day
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Participant Flow for 2 periods

Period 1:   Open-label Phase
    1 Tramadol Once A Day     2 Placebo  
STARTED     1028 [1]   0 [2]
Entered run-in Period     1027     0  
Received Open-Label Treatment     1023     0  
COMPLETED     646 [3]   0  
NOT COMPLETED     382     0  
Adverse Event                 225                 0  
Lack of Efficacy                 28                 0  
Withdrawal by Subject                 48                 0  
Physician Decision                 20                 0  
Administrative reason                 1                 0  
Protocol Violation                 47                 0  
Did not complete wash-out period                 12                 0  
enrolled in error (immediately D/C)                 1                 0  
[1] Enrolled. Population described in the baseline characteristics is 1023 patients (Open-Label safety).
[2] No Placebo arm during open-label phase.
[3] Randomized in double-blind phase

Period 2:   Double-blind Phase
    1 Tramadol Once A Day     2 Placebo  
STARTED     432 [1]   214 [2]
COMPLETED     326     165  
NOT COMPLETED     106     49  
Adverse Event                 44                 11  
Lack of Efficacy                 34                 22  
Withdrawal by Subject                 23                 6  
Physician Decision                 4                 7  
Administrative reason                 1                 3  
[1] Of the 646 patients who completed the Open-Label phase, 432 were randomized to Tramadol Once A Day
[2] Of the 646 patients who completed the Open-Label phase, 214 were randomized to Placebo



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.
Total Total of all reporting groups

Baseline Measures
    1 Tramadol Once A Day     2 Placebo     Total  
Number of Participants  
[units: participants]
  432     214     646  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     252     116     368  
>=65 years     180     98     278  
Age  
[units: years]
Mean ± Standard Deviation
  61.8  ± 9.0     62.3  ± 8.9     62.0  ± 9.0  
Gender  
[units: participants]
     
Female     275     133     408  
Male     157     81     238  



  Outcome Measures
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1.  Primary:   Pain Intensity Score as Measured by the 11-point Pain Intensity-Numerical Rating Scale Score at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: 12 weeks ]

Measure Type Primary
Measure Title Pain Intensity Score as Measured by the 11-point Pain Intensity-Numerical Rating Scale Score at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description The Pain Intensity Score is an 11-point pain intensity numerical rating scale ranging from 0: no pain to 10: worst possible pain. The mean score at the end of the study (week 12 or time of discontinuation) was calculated.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
Pain Intensity Score as Measured by the 11-point Pain Intensity-Numerical Rating Scale Score at the End of the Study (Week 12 or Time of Discontinuation)  
[units: Points on a scale]
Mean ± Standard Deviation
  4.3  ± 2.5     4.8  ± 2.4  

No statistical analysis provided for Pain Intensity Score as Measured by the 11-point Pain Intensity-Numerical Rating Scale Score at the End of the Study (Week 12 or Time of Discontinuation)



2.  Secondary:   Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment   [ Time Frame: 6 weeks ]

Measure Type Secondary
Measure Title Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment
Measure Description The Pain Intensity Score is an 11-point pain intensity numerical rating scale ranging from 0: no pain to 10: worst possible pain
Time Frame 6 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment  
[units: Points on a scale]
Mean ± Standard Deviation
  4.0  ± 2.2     4.5  ± 2.2  

No statistical analysis provided for Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment



3.  Secondary:   Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description Pain Intensity Score (an 11-point pain intensity numerical rating scale ranging from 0: no pain to 10: worst possible pain) was stratified by final dose level, at week 12 or time of discontinuation. The final optimum dose level based upon efficacy and tolerability was kept for the entire study. The mean score was calculated.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.
Tramadol Once A Day 200 mg No text entered.
Tramadol Once A Day 300 mg No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo     Tramadol Once A Day 200 mg     Tramadol Once A Day 300 mg  
Number of Participants Analyzed  
[units: participants]
  431     214     106     325  
Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)  
[units: Points on a scale]
Mean ± Standard Deviation
  4.3  ± 2.5     4.8  ± 2.4     4.1  ± 2.4     4.4  ± 2.6  

No statistical analysis provided for Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)



4.  Secondary:   WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description Mean WOMAC Pain Subscale score at week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 5-point Likert-scale ranging from no difficulty to extreme difficulty (0-none; 1-slight; 2-moderate; 3-severe; 4-extreme). The WOMAC pain subscale results from the sum of 5 pain questions. The maximum total score is 20.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)  
[units: Points on a scale]
Mean ± Standard Deviation
  6.9  ± 4.0     7.5  ± 4.1  

No statistical analysis provided for WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)



5.  Secondary:   WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description Mean WOMAC Physical Function Subscale score at week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 5-point Likert-scale ranging from no difficulty to extreme difficulty (0-none; 1-slight; 2-moderate; 3-severe; 4-extreme). The WOMAC Physical Function subscale results from the sum of 17 physical function questions and the maximum possible score is 68.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)  
[units: Points on a scale]
Mean ± Standard Deviation
  24.9  ± 13.4     27.5  ± 13.8  

No statistical analysis provided for WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)



6.  Secondary:   Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description This assessment of overall status integrates the effect of the treatment on pain, side effects, and the patient's expectation of pain relief. It is made using a 7-point categorical scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse)
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  425     210  
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)  
[units: participants]
   
1 = very much improved     86     27  
2 = much improved     148     59  
3 = minimally improved     108     58  
4 = no change     49     42  
5 = minimally worse     17     13  
6 = much worse     17     8  
7 = very much worse     0     3  

No statistical analysis provided for Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)



7.  Secondary:   Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)   [ Time Frame: week 12 ]

Measure Type Secondary
Measure Title Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)
Measure Description This assessment of overall impression of study drug is made using a 7-point categorical scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse)
Time Frame week 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  423     210  
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)  
[units: participants]
   
1 = very much improved     76     25  
2 = much improved     154     71  
3 = minimally improved     108     49  
4 = no change     49     41  
5 = minimally worse     21     17  
6 = much worse     13     5  
7 = very much worse     1     2  
Not determined     1     0  

No statistical analysis provided for Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation)



8.  Secondary:   Time to Response   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title Time to Response
Measure Description Response was defined as a decrease of ≥1 point in an 11-point PINRS (11-point pain intensity numerical rating scale ranging from 0: no pain to 10: worst possible pain) from baseline to the last visit. The time to response was estimated using Kaplan-Meier analysis and a 95% CI for the median time was calculated.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
Time to Response  
[units: days]
Median ( 95% Confidence Interval )
   
1-point response     14  
  ( 14 to 14 )  
  14  
  ( 14 to 14 )  
2-point response     14  
  ( 14 to 15 )  
  15  
  ( 14 to 16 )  
3-point response     16  
  ( 15 to 35 )  
  39  
  ( 35 to 56 )  
4-point response     15  
  ( 14 to 15 )  
  35  
  ( 35 to 56 )  
5-point response     35  
  ( 15 to 35 )  
  77  
  ( 56 to 99 )  

No statistical analysis provided for Time to Response



9.  Secondary:   Discontinuation Due to Lack of Efficacy   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title Discontinuation Due to Lack of Efficacy
Measure Description The number of patients who discontinued due to lack of efficacy was reported.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
Discontinuation Due to Lack of Efficacy  
[units: participants]
  34     22  

No statistical analysis provided for Discontinuation Due to Lack of Efficacy



10.  Secondary:   Discontinuation Due to Adverse Events   [ Time Frame: 12 weeks ]

Measure Type Secondary
Measure Title Discontinuation Due to Adverse Events
Measure Description The number of patients who discontinued due to adverse events (AEs). An AE is defined as any untoward medical event that occurs during the course of a clinical investigation in which a patient is administered a pharmaceutical or other therapeutic product. Its occurrence does not necessarily imply a causal relationship with the treatment.
Time Frame 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis population: all randomized patients who received at least one dose of the randomized study medication regardless of the status of the post-dosing assessment.

Reporting Groups
  Description
1 Tramadol Once A Day No text entered.
2 Placebo No text entered.

Measured Values
    1 Tramadol Once A Day     2 Placebo  
Number of Participants Analyzed  
[units: participants]
  431     214  
Discontinuation Due to Adverse Events  
[units: participants]
  44     12  

No statistical analysis provided for Discontinuation Due to Adverse Events




  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked 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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked 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. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Director of Regulatory Affairs
Organization: Labopharm Inc.
phone: 1 450 686 1017


Publications of Results:

Responsible Party: Labopharm Inc.
ClinicalTrials.gov Identifier: NCT00833794     History of Changes
Other Study ID Numbers: MDT3-005
Study First Received: January 29, 2009
Results First Received: April 9, 2009
Last Updated: April 25, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Canada: Health Canada
Romania: National Medicines Agency