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

History of Changes

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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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

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Prior to submitting results communications, the investigator shall allow Labopharm at least 30 days to review the proposed communication. If the proposed publication/disclosure risks Labopharm’s ability to patent any invention related to the study, the publication or disclosure will be modified or delayed to allow Labopharm to seek patent protection. This statement does not give Labopharm any editorial rights other than to restrict the disclosure of Labopharm’s confidential information.

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:

Burch F, Fishman R, Messina N, Corser B, Radulescu F, Sarbu A, Craciun-Nicodin MM, Chiriac R, Beaulieu A, Rodrigues J, Beignot-Devalmont P, Duplan A, Robertson S, Fortier L, Bouchard S. A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis. J Pain Symptom Manage. 2007 Sep;34(3):328-38. Epub 2007 Jun 21.

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

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