Trial Outcomes & Findings for A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up) (NCT NCT00852917)
NCT ID: NCT00852917
Last Updated: 2012-04-30
Results Overview
3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.
COMPLETED
PHASE3
552 participants
12 weeks
2012-04-30
Participant Flow
Participant milestones
| Measure |
1: Tramadol Once A Day 100mg
|
2: Tramadol Once A Day 200mg
|
3: Tramadol Once A Day 300mg
|
4: Placebo
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
106
|
111
|
108
|
227
|
|
Overall Study
COMPLETED
|
62
|
65
|
50
|
134
|
|
Overall Study
NOT COMPLETED
|
44
|
46
|
58
|
93
|
Reasons for withdrawal
| Measure |
1: Tramadol Once A Day 100mg
|
2: Tramadol Once A Day 200mg
|
3: Tramadol Once A Day 300mg
|
4: Placebo
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
13
|
20
|
35
|
17
|
|
Overall Study
Lack of Efficacy
|
21
|
11
|
11
|
47
|
|
Overall Study
Withdrawal by Subject
|
4
|
8
|
10
|
9
|
|
Overall Study
Physician Decision
|
6
|
7
|
2
|
19
|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up)
Baseline characteristics by cohort
| Measure |
1: Tramadol Once A Day 100mg
n=106 Participants
|
2: Tramadol Once A Day 200mg
n=111 Participants
|
3: Tramadol Once A Day 300mg
n=108 Participants
|
4: Placebo
n=227 Participants
|
Total
n=552 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
|
0 Participants
n=4 Participants
|
0.0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
58 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
136 Participants
n=4 Participants
|
327.0 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
48 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
225.0 Participants
n=21 Participants
|
|
Age Continuous
|
62.9 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
61.1 years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
60.3 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
61.1 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
61.3 years
STANDARD_DEVIATION 9.3 • n=21 Participants
|
|
Sex: Female, Male
Female
|
65 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
140 Participants
n=4 Participants
|
344.0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
208.0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale)
3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Patient Global Rating of Pain for the Study Period (12 Weeks)
Very effective
|
19 participants
|
25 participants
|
27 participants
|
28 participants
|
|
Patient Global Rating of Pain for the Study Period (12 Weeks)
Effective
|
49 participants
|
55 participants
|
57 participants
|
102 participants
|
|
Patient Global Rating of Pain for the Study Period (12 Weeks)
Ineffective
|
34 participants
|
27 participants
|
21 participants
|
93 participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale). Missing Values at Last Visit Imputed by Individual Last Post Baseline Value.
Percentage of difference in WOMAC Pain Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale (VAS) ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 of the questions.
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
|
41.6 Percentage difference in WOMAC Pain
Standard Deviation 50.2
|
42.8 Percentage difference in WOMAC Pain
Standard Deviation 46.4
|
46.0 Percentage difference in WOMAC Pain
Standard Deviation 39.9
|
32.3 Percentage difference in WOMAC Pain
Standard Deviation 48.2
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale). Missing Values at Last Visit Imputed by Individual Last Post Baseline Value.
Percentage of difference in WOMAC Physical Function Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no difficulty (0mm) to extreme difficulty (100mm). The WOMAC Physical Function subscale results from the sum of 17 of the questions.
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
|
42.3 Percentage difference in WOMAC Physical
Standard Deviation 46.1
|
42.0 Percentage difference in WOMAC Physical
Standard Deviation 39.5
|
38.7 Percentage difference in WOMAC Physical
Standard Deviation 70.0
|
30.9 Percentage difference in WOMAC Physical
Standard Deviation 44.4
|
SECONDARY outcome
Timeframe: Week 0, week 3, week 6Population: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale)
Percentage of difference in WOMAC Pain Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 0 (Visit 2)
|
30.0 Percentage difference in WOMAC Pain
Standard Deviation 41.1
|
34.5 Percentage difference in WOMAC Pain
Standard Deviation 41.5
|
33.0 Percentage difference in WOMAC Pain
Standard Deviation 44.6
|
19.4 Percentage difference in WOMAC Pain
Standard Deviation 36.5
|
|
Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 3 (Visit 3)
|
56.4 Percentage difference in WOMAC Pain
Standard Deviation 39.2
|
46.4 Percentage difference in WOMAC Pain
Standard Deviation 37.7
|
51.7 Percentage difference in WOMAC Pain
Standard Deviation 41.9
|
37.8 Percentage difference in WOMAC Pain
Standard Deviation 40.0
|
|
Percentage Change in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 6 (Visit 4)
|
58.2 Percentage difference in WOMAC Pain
Standard Deviation 39.3
|
48.8 Percentage difference in WOMAC Pain
Standard Deviation 39.8
|
57.2 Percentage difference in WOMAC Pain
Standard Deviation 37.6
|
44.7 Percentage difference in WOMAC Pain
Standard Deviation 41.8
|
SECONDARY outcome
Timeframe: Week 0, week 3, week 6Population: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale)
Percentage of difference in WOMAC Physical Function Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales. The WOMAC Physical Function Subscale comprises 17 questions each rated on a 100mm visual analog scale (VAS) ranging from no difficulty (0mm) to extreme difficulty (100mm).
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 6 (Visit 4)
|
56.2 Percentage difference in WOMAC Physical
Standard Deviation 37.6
|
44.2 Percentage difference in WOMAC Physical
Standard Deviation 40.0
|
53.5 Percentage difference in WOMAC Physical
Standard Deviation 58.9
|
39.5 Percentage difference in WOMAC Physical
Standard Deviation 41.3
|
|
Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 0 (Visit 2)
|
32.0 Percentage difference in WOMAC Physical
Standard Deviation 36.8
|
29.8 Percentage difference in WOMAC Physical
Standard Deviation 35.6
|
34.5 Percentage difference in WOMAC Physical
Standard Deviation 35.9
|
17.2 Percentage difference in WOMAC Physical
Standard Deviation 36.0
|
|
Percentage Change in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Week 3 (Visit 3)
|
54.9 Percentage difference in WOMAC Physical
Standard Deviation 37.9
|
43.5 Percentage difference in WOMAC Physical
Standard Deviation 37.1
|
50.4 Percentage difference in WOMAC Physical
Standard Deviation 36.8
|
34.4 Percentage difference in WOMAC Physical
Standard Deviation 38.6
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale). Missing Values at Last Visit Imputed by Individual Last Post Baseline Value.
Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Lunchtime (last individual visit)
|
35.1 mm
Standard Deviation 29.4
|
32.0 mm
Standard Deviation 25.2
|
34.4 mm
Standard Deviation 28.6
|
38.9 mm
Standard Deviation 30.5
|
|
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Bed time (last individual visit)
|
37.0 mm
Standard Deviation 31.4
|
34.3 mm
Standard Deviation 26.0
|
34.7 mm
Standard Deviation 29.9
|
41.9 mm
Standard Deviation 32.6
|
|
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Before next morning dose (last individual visit)
|
35.9 mm
Standard Deviation 31.3
|
34.3 mm
Standard Deviation 27.6
|
34.8 mm
Standard Deviation 29.1
|
40.6 mm
Standard Deviation 31.5
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The analysis was performed using the full analysis population (All randomized patients who received at least one dose of the assigned study medication and had at least one post Baseline assessment of any functional scale)
The Investigator Global Rating of Pain is a 3-item Likert-scale to answer the following question: "How do you rate this patient's overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective".
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=103 Participants
|
2: Tramadol Once A Day 200mg
n=107 Participants
|
3: Tramadol Once A Day 300mg
n=105 Participants
|
4: Placebo
n=224 Participants
|
|---|---|---|---|---|
|
Investigator Global Rating of Pain Relief
Very effective
|
20 participants
|
26 participants
|
26 participants
|
26 participants
|
|
Investigator Global Rating of Pain Relief
Effective
|
46 participants
|
53 participants
|
61 participants
|
102 participants
|
|
Investigator Global Rating of Pain Relief
Ineffective
|
35 participants
|
28 participants
|
17 participants
|
95 participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Safety population: all randomized patients who received at least one dose of the assigned study medication.
Reasons for withdrawal from the trial were collected
Outcome measures
| Measure |
1: Tramadol Once A Day 100mg
n=106 Participants
|
2: Tramadol Once A Day 200mg
n=111 Participants
|
3: Tramadol Once A Day 300mg
n=108 Participants
|
4: Placebo
n=227 Participants
|
|---|---|---|---|---|
|
Dropout Rate
Lack of efficacy
|
19.8 percentage of participants
|
9.9 percentage of participants
|
10.2 percentage of participants
|
20.7 percentage of participants
|
|
Dropout Rate
Patient request
|
3.8 percentage of participants
|
7.2 percentage of participants
|
9.3 percentage of participants
|
4.0 percentage of participants
|
|
Dropout Rate
Investigator initiated discontinuation
|
5.7 percentage of participants
|
6.3 percentage of participants
|
1.9 percentage of participants
|
8.4 percentage of participants
|
|
Dropout Rate
Adverse events
|
12.3 percentage of participants
|
18.0 percentage of participants
|
32.4 percentage of participants
|
7.5 percentage of participants
|
|
Dropout Rate
Death
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0.4 percentage of participants
|
Adverse Events
1: Tramadol Once A Day 100mg
2: Tramadol Once A Day 200mg
3: Tramadol Once A Day 300mg
4: Placebo
Serious adverse events
| Measure |
1: Tramadol Once A Day 100mg
|
2: Tramadol Once A Day 200mg
|
3: Tramadol Once A Day 300mg
|
4: Placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Small intestinal obstruction Not Otherwise Specified (NOS)
|
0.94%
1/106 • Number of events 1
|
0.00%
0/111
|
0.00%
0/108
|
0.00%
0/227
|
|
Gastrointestinal disorders
Gastritis Not Otherwise Specified (NOS)
|
0.00%
0/106
|
0.00%
0/111
|
0.93%
1/108 • Number of events 1
|
0.00%
0/227
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/106
|
0.00%
0/111
|
0.00%
0/108
|
0.44%
1/227 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/106
|
0.00%
0/111
|
0.00%
0/108
|
0.44%
1/227 • Number of events 1
|
Other adverse events
| Measure |
1: Tramadol Once A Day 100mg
|
2: Tramadol Once A Day 200mg
|
3: Tramadol Once A Day 300mg
|
4: Placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
10.4%
11/106 • Number of events 11
|
14.4%
16/111 • Number of events 22
|
9.3%
10/108 • Number of events 13
|
1.3%
3/227 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
10.4%
11/106 • Number of events 11
|
9.0%
10/111 • Number of events 13
|
18.5%
20/108 • Number of events 21
|
4.0%
9/227 • Number of events 13
|
|
Gastrointestinal disorders
Nausea
|
11.3%
12/106 • Number of events 14
|
19.8%
22/111 • Number of events 34
|
25.9%
28/108 • Number of events 36
|
5.7%
13/227 • Number of events 18
|
|
Nervous system disorders
Somnolence
|
8.5%
9/106 • Number of events 11
|
15.3%
17/111 • Number of events 19
|
12.0%
13/108 • Number of events 13
|
0.88%
2/227 • Number of events 2
|
|
Nervous system disorders
Headache
|
5.7%
6/106 • Number of events 8
|
9.0%
10/111 • Number of events 15
|
5.6%
6/108 • Number of events 6
|
7.9%
18/227 • Number of events 21
|
Additional Information
Director of Regulatory Affairs
Labopharm Inc.
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