Trial Outcomes & Findings for 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 (NCT NCT00833794)

NCT ID: NCT00833794

Last Updated: 2012-04-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1028 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2012-04-30

Participant Flow

Participant milestones

Measure	1 Tramadol Once A Day	2 Placebo
Open-label Phase STARTED	1028	0
Open-label Phase Entered run-in Period	1027	0
Open-label Phase Received Open-Label Treatment	1023	0
Open-label Phase COMPLETED	646	0
Open-label Phase NOT COMPLETED	382	0
Double-blind Phase STARTED	432	214
Double-blind Phase COMPLETED	326	165
Double-blind Phase NOT COMPLETED	106	49

Reasons for withdrawal

Measure	1 Tramadol Once A Day	2 Placebo
Open-label Phase Adverse Event	225	0
Open-label Phase Lack of Efficacy	28	0
Open-label Phase Withdrawal by Subject	48	0
Open-label Phase Physician Decision	20	0
Open-label Phase Administrative reason	1	0
Open-label Phase Protocol Violation	47	0
Open-label Phase Did not complete wash-out period	12	0
Open-label Phase enrolled in error (immediately D/C)	1	0
Double-blind Phase Adverse Event	44	11
Double-blind Phase Lack of Efficacy	34	22
Double-blind Phase Withdrawal by Subject	23	6
Double-blind Phase Physician Decision	4	7
Double-blind Phase Administrative reason	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	1 Tramadol Once A Day n=432 Participants	2 Placebo n=214 Participants	Total n=646 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	252 Participants n=5 Participants	116 Participants n=7 Participants	368 Participants n=5 Participants
Age, Categorical >=65 years	180 Participants n=5 Participants	98 Participants n=7 Participants	278 Participants n=5 Participants
Age Continuous	61.8 years STANDARD_DEVIATION 9.0 • n=5 Participants	62.3 years STANDARD_DEVIATION 8.9 • n=7 Participants	62.0 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	275 Participants n=5 Participants	133 Participants n=7 Participants	408 Participants n=5 Participants
Sex: Female, Male Male	157 Participants n=5 Participants	81 Participants n=7 Participants	238 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
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)	4.3 Points on a scale Standard Deviation 2.5	4.8 Points on a scale Standard Deviation 2.4	—	—

SECONDARY outcome

Timeframe: 6 weeks

Population: 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.

The Pain Intensity Score is an 11-point pain intensity numerical rating scale ranging from 0: no pain to 10: worst possible pain

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Pain Intensity Score (11-point PINRS) After 6 Weeks of Maintenance Treatment	4.0 Points on a scale Standard Deviation 2.2	4.5 Points on a scale Standard Deviation 2.2	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg n=106 Participants	Tramadol Once A Day 300 mg n=325 Participants
Pain Intensity Score Stratified by Dose, at the End of the Study (Week 12 or Time of Discontinuation)	4.3 Points on a scale Standard Deviation 2.5	4.8 Points on a scale Standard Deviation 2.4	4.1 Points on a scale Standard Deviation 2.4	4.4 Points on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
WOMAC Pain Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)	6.9 Points on a scale Standard Deviation 4.0	7.5 Points on a scale Standard Deviation 4.1	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
WOMAC Physical Function Subscale Score at the End of the Study (Week 12 or Time of Discontinuation)	24.9 Points on a scale Standard Deviation 13.4	27.5 Points on a scale Standard Deviation 13.8	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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)

Outcome measures

Measure	1 Tramadol Once A Day n=425 Participants	2 Placebo n=210 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 1 = very much improved	86 participants	27 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 6 = much worse	17 participants	8 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 7 = very much worse	0 participants	3 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 2 = much improved	148 participants	59 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 3 = minimally improved	108 participants	58 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 4 = no change	49 participants	42 participants	—	—
Patient Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 5 = minimally worse	17 participants	13 participants	—	—

SECONDARY outcome

Timeframe: week 12

Population: 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.

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)

Outcome measures

Measure	1 Tramadol Once A Day n=423 Participants	2 Placebo n=210 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 3 = minimally improved	108 participants	49 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 1 = very much improved	76 participants	25 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 2 = much improved	154 participants	71 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 4 = no change	49 participants	41 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 5 = minimally worse	21 participants	17 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 6 = much worse	13 participants	5 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) 7 = very much worse	1 participants	2 participants	—	—
Physician Global Impression of Change at the End of the Study (Week 12 or Time of Discontinuation) Not determined	1 participants	0 participants	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Time to Response 1-point response	14 days Interval 14.0 to 14.0	14 days Interval 14.0 to 14.0	—	—
Time to Response 2-point response	14 days Interval 14.0 to 15.0	15 days Interval 14.0 to 16.0	—	—
Time to Response 3-point response	16 days Interval 15.0 to 35.0	39 days Interval 35.0 to 56.0	—	—
Time to Response 4-point response	15 days Interval 14.0 to 15.0	35 days Interval 35.0 to 56.0	—	—
Time to Response 5-point response	35 days Interval 15.0 to 35.0	77 days Interval 56.0 to 99.0	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

The number of patients who discontinued due to lack of efficacy was reported.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Discontinuation Due to Lack of Efficacy	34 participants	22 participants	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	1 Tramadol Once A Day n=431 Participants	2 Placebo n=214 Participants	Tramadol Once A Day 200 mg	Tramadol Once A Day 300 mg
Discontinuation Due to Adverse Events	44 participants	12 participants	—	—

Adverse Events

1 Tramadol Once A Day

Serious events: 9 serious events

Other events: 136 other events

Deaths: 0 deaths

2 Placebo

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	1 Tramadol Once A Day	2 Placebo
Nervous system disorders Grand mal convulsion	0.10% 1/1023 • Number of events 1	0.00% 0/214
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.10% 1/1023 • Number of events 1	0.00% 0/214
Infections and infestations Hepatitis	0.10% 1/1023 • Number of events 1	0.00% 0/214
Renal and urinary disorders Renal impairment	0.10% 1/1023 • Number of events 1	0.00% 0/214
Musculoskeletal and connective tissue disorders Popliteal bursitis	0.10% 1/1023 • Number of events 1	0.00% 0/214
Nervous system disorders Ischaemic stroke	0.00% 0/1023	0.47% 1/214 • Number of events 1
Gastrointestinal disorders Diverticulitis	0.10% 1/1023 • Number of events 1	0.00% 0/214
Cardiac disorders Angina unstable	0.10% 1/1023 • Number of events 1	0.00% 0/214
Nervous system disorders Syncope	0.10% 1/1023 • Number of events 1	0.00% 0/214
General disorders Chest pain	0.10% 1/1023 • Number of events 1	0.00% 0/214
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.10% 1/1023 • Number of events 1	0.00% 0/214

Other adverse events

Measure	1 Tramadol Once A Day	2 Placebo
Gastrointestinal disorders Nausea	15.3% 66/432 • Number of events 86	5.6% 12/214 • Number of events 12
Gastrointestinal disorders Constipation	14.1% 61/432 • Number of events 73	4.2% 9/214 • Number of events 12
Nervous system disorders Dizziness	6.0% 26/432 • Number of events 28	3.3% 7/214 • Number of events 8
Nervous system disorders Somnolence	6.7% 29/432 • Number of events 40	3.7% 8/214 • Number of events 9

Additional Information

Director of Regulatory Affairs

Labopharm Inc.

Phone: 1 450 686 1017

Results disclosure agreements

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

Restriction type: OTHER