Trial Outcomes & Findings for A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol HCl / Contramid® Tablets to Twice Daily Tramadol HCl (SR) for the Treatment of Osteoarthritis of the Knee (NCT NCT00950651)

NCT ID: NCT00950651

Last Updated: 2012-04-30

Results Overview

The WOMAC is a statistically validated, 24-item questionnaire assessing current OA symptoms and functional limitations. The Pain subscale score consists of 5 items each rated on a 100mm VAS scale (0mm=no pain to 100mm=extreme pain). In case of premature discontinuation, the last assessment was used to calculate the percentage of change.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

431 participants

Primary outcome timeframe

Baseline to week 12

Results posted on

2012-04-30

Participant Flow

Participant milestones

Participant milestones
Measure
Tramadol HCl Contramid® Once A Day
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Overall Study
STARTED
215
216
Overall Study
COMPLETED
184
181
Overall Study
NOT COMPLETED
31
35

Reasons for withdrawal

Reasons for withdrawal
Measure
Tramadol HCl Contramid® Once A Day
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Overall Study
Adverse Event
17
20
Overall Study
Death
1
0
Overall Study
Lack of Efficacy
2
2
Overall Study
Protocol Violation
3
4
Overall Study
Withdrawal by Subject
8
9

Baseline Characteristics

A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol HCl / Contramid® Tablets to Twice Daily Tramadol HCl (SR) for the Treatment of Osteoarthritis of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Tramadol HCl Contramid® Once A Day
n=215 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=215 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Total
n=430 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
121 Participants
n=5 Participants
137 Participants
n=7 Participants
258 Participants
n=5 Participants
Age, Categorical
>=65 years
94 Participants
n=5 Participants
78 Participants
n=7 Participants
172 Participants
n=5 Participants
Age Continuous
61.9 years
STANDARD_DEVIATION 8.8 • n=5 Participants
59.9 years
STANDARD_DEVIATION 9.1 • n=7 Participants
60.9 years
STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male
Female
181 Participants
n=5 Participants
176 Participants
n=7 Participants
357 Participants
n=5 Participants
Sex: Female, Male
Male
34 Participants
n=5 Participants
39 Participants
n=7 Participants
73 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The WOMAC is a statistically validated, 24-item questionnaire assessing current OA symptoms and functional limitations. The Pain subscale score consists of 5 items each rated on a 100mm VAS scale (0mm=no pain to 100mm=extreme pain). In case of premature discontinuation, the last assessment was used to calculate the percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in WOMAC Pain Subscale Score at Week 12
58.3 percentage of change
Standard Deviation 29.9
58.7 percentage of change
Standard Deviation 27.0

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Each day before morning dose, patients assessed arthritis pain in worst knee in a diary using a 5-point rating scale ranging from none to severe. A median score was estimated for each patient each week and re-categorized into different degrees of pain (rounding off to the closest integer). Results are of 12th week (day 78-84).

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
None
20 participants
19 participants
Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
Barely noticeable
42 participants
33 participants
Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
Mild
35 participants
40 participants
Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
Moderate
35 participants
32 participants
Arthritis Pain at the End of Dosing Interval (24-hour Efficacy)
Severe
2 participants
5 participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The WOMAC is a statistically validated, 24-item questionnaire assessing current OA symptoms and functional limitations. Stiffness subscale score consists of 2 items each rated on 100mm VAS scale (0mm=no stiffness to 100mm=extreme stiffness). In case of premature discontinuation, the last assessment was used to calculate the percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in WOMAC Stiffness Subscale Score at Week 12
49.1 percentage of change
Standard Deviation 60.8
49.5 percentage of change
Standard Deviation 37.9

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The WOMAC is a statistically validated, 24-item questionnaire assessing current OA symptoms and functional limitations. Physical Function subscale score consists of 17 items rated on a 100mm VAS scale (0mm=no difficulty to 100mm=extreme difficulty). In case of premature discontinuation, the last assessment was used to calculate percentage of change

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in WOMAC Physical Function Subscale Score at Week 12
50.8 percentage of change
Standard Deviation 32.5
49.8 percentage of change
Standard Deviation 29.7

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The WOMAC is a statistically validated, 24-item questionnaire assessing current OA symptoms and functional limitations. Each item is rated on a 100mm VAS scale (0mm=no pain/stiffness/difficulty to 100mm=extreme no pain/stiffness/difficulty). In case of premature discontinuation, the last assessment was used to calculate percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in WOMAC Total Score at Week 12
52.9 percentage of change
Standard Deviation 30.9
52.0 percentage of change
Standard Deviation 28.5

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Pain Visual Analogue Scales: Current Pain. Patients indicated their current pain using a 100mm VAS scale ranging from 0=no pain to 100=extreme pain. The percentage of change in current pain was calculated from baseline to week 12. In case of premature discontinuation, the last assessment was used to calculate percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in Current Pain at Week 12
35.1 percentage of change
Standard Deviation 23.8
34.6 percentage of change
Standard Deviation 23.5

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients indicated their Least Pain Within Last 24 Hours using a 100mm VAS scale ranging from 0=no pain to 100=extreme pain. The percentage of change was calculated from baseline to week 12. In case of premature discontinuation, the last assessment was used to calculate percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in Least Pain Within Last 24 Hours at Week 12
21.6 percentage of change
Standard Deviation 21.3
23.5 percentage of change
Standard Deviation 21.2

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients indicated their Worst Pain Within Last 24 Hours using a 100mm VAS scale ranging from 0=no pain to 100=extreme pain. The percentage of change was calculated from baseline to week 12. In case of premature discontinuation, the last assessment was used to calculate percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in Worst Pain Within Last 24 Hours at Week 12
38.6 percentage of change
Standard Deviation 27.9
39.2 percentage of change
Standard Deviation 26.3

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients indicated their Average Pain Within Last 24 Hours using a 100mm VAS scale ranging from 0=no pain to 100=extreme pain. The percentage of change was calculated from baseline to week 12. In case of premature discontinuation, the last assessment was used to calculate percentage of change.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in Average Pain Within Last 24 Hours at Week 12
30.1 percentage of change
Standard Deviation 22.0
30.7 percentage of change
Standard Deviation 19.7

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The walking test is a measure of how many seconds it takes the patient to walk a distance of 15 meters. The change from baseline to week 12 was calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Percentage of Change From Baseline in Walking Time for 15 Meters at Week 12
5.639 percentage of change
Standard Deviation 6.231
4.738 percentage of change
Standard Deviation 5.495

SECONDARY outcome

Timeframe: 12 Weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The Patient Global Rating of Pain is a Likert-scale that answers the question: "How do you rate overall pain relief with the drug?" with 4 possible answers that were dichotomized: "very effective", "effective", and "somewhat effective" were summarized to "effective"; "not effective" remained unchanged.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Global Rating of Pain Relief at Week 12
Effective
160 participants
151 participants
Patient Global Rating of Pain Relief at Week 12
Not effective
1 participants
2 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients were asked: "How have any side effects you may have felt from the drug interfered with day-to-day activities?" with 4 possible answers: "Significantly", "Somewhat", "Minimally", "Not at all".

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Global Assessment: Side Effects Interfering With Day to Day Activities at Week 12
Significantly
7 participants
2 participants
Patient Global Assessment: Side Effects Interfering With Day to Day Activities at Week 12
Somewhat
15 participants
18 participants
Patient Global Assessment: Side Effects Interfering With Day to Day Activities at Week 12
Minimally
39 participants
34 participants
Patient Global Assessment: Side Effects Interfering With Day to Day Activities at Week 12
Not at all
100 participants
99 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients who have previously taken tramadol HCl were asked to compare how they compare the current pain relief to the pain relief felt when previously taking tramadol, using a 4-point Likert-scale: "Worse than before", "Same as before", "Somewhat better now", or "Much better now".

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Global Assessment: Current Pain Relief Versus Pain Relief During Previous Tramadol Treatment at Week 12
Worse than before
0 participants
0 participants
Patient Global Assessment: Current Pain Relief Versus Pain Relief During Previous Tramadol Treatment at Week 12
Same as before
4 participants
2 participants
Patient Global Assessment: Current Pain Relief Versus Pain Relief During Previous Tramadol Treatment at Week 12
Somewhat better now
11 participants
3 participants
Patient Global Assessment: Current Pain Relief Versus Pain Relief During Previous Tramadol Treatment at Week 12
Much better now
8 participants
8 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

Patients who have previously taken tramadol HCl were asked: "Compared to when you were previously taking tramadol, how have any side effects you have felt during this study interfered with your day-to-day activities?". Possible answers were: "Interfered much less now", "Interfered somewhat less now", "Same as before", "Interfered more now".

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Global Assessment: Current Interfering Side Effects Versus Pain Relief During Previous Tramadol Treatment at Week 12
Interfered much less now
4 participants
8 participants
Patient Global Assessment: Current Interfering Side Effects Versus Pain Relief During Previous Tramadol Treatment at Week 12
Interfered somewhat less now
2 participants
1 participants
Patient Global Assessment: Current Interfering Side Effects Versus Pain Relief During Previous Tramadol Treatment at Week 12
Same as before
13 participants
4 participants
Patient Global Assessment: Current Interfering Side Effects Versus Pain Relief During Previous Tramadol Treatment at Week 12
Interfered more now
3 participants
0 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The physician was asked to indicate his overall assessment of the formulation the patient was taking using a 4-point Likert-scale dichotomized for the analysis: Very Effective, Effective, and Somewhat Effective were summarized to Effective; Ineffective remained unchanged.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Physician Overall Rating: Overall Assessment at Week 12
Effective
160 participants
150 participants
Physician Overall Rating: Overall Assessment at Week 12
Not effective
1 participants
3 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

The physician was asked to indicate the effectiveness of pain control 24 hours after the most recent dose of tramadol using a 4-point Likert-scale, dichotomized for the analysis: Very Effective, Effective, Somewhat Effective were summarized to Effective; Ineffective remained unchanged.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Physician Overall Rating: Effectiveness of Pain Control 24 Hours After the Most Recent Dose of Tramadol at Week 12
Effective
160 participants
151 participants
Physician Overall Rating: Effectiveness of Pain Control 24 Hours After the Most Recent Dose of Tramadol at Week 12
Not effective
1 participants
2 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

As part of the daily diary for the entire study, patients rated the arthritis pain in their worst knee using a five-point scale ranging from 1=none to 5=severe. Mean scores summarizing the entries of the preceding period were calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Diary: Pain (Between Visit Means) at Week 12
2.74 Units on a scale
Standard Deviation 0.98
2.86 Units on a scale
Standard Deviation 1.08

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

As part of the daily diary for the entire study, patients rated the stiffness in their worst knee using a five-point scale ranging from 1=none to 5=severe. Mean scores summarizing the entries of the preceding period were calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Diary: Stiffness (Between Visit Means) at Week 12
2.67 Units on a scale
Standard Deviation 0.96
2.82 Units on a scale
Standard Deviation 1.06

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

As part of the daily diary for the entire study, patients rated their ability to get things done with their worst knee using a five-point scale ranging from: 1=No problem to 5=A lot of things didn't get done. Mean scores summarizing the entries of the preceding period were calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Diary: Ability Getting Things Done (Between Visit Means) at Week 12
2.41 Units on a scale
Standard Deviation 1.14
2.34 Units on a scale
Standard Deviation 1.18

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

As part of the daily diary for the entire study, patients rated their difficulty walking with their worst knee using a five-point scale ranging from 1=No problem to 5=Severe difficulty. Mean scores summarizing the entries of the preceding period were calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Diary: Difficulty With Walking (Between Visit Means) at Week 12
2.79 Units on a scale
Standard Deviation 1.05
2.85 Units on a scale
Standard Deviation 1.11

SECONDARY outcome

Timeframe: 12 weeks

Population: Per protocol population: patients who completed study, had no major protocol deviations before/during trial and had primary efficacy variable rating at end of study. Early drop-outs due to AEs / lack of efficacy were included if they took study drug for \>2weeks in maintenance phase and had efficacy assessments within 2 days after end of study drug.

As part of the daily diary for the entire study, patients rated their difficulty with stairs with their worst knee using a five-point scale ranging from 1=No problem to 5=Severe difficulty. Mean scores summarizing the entries of the preceding period were calculated.

Outcome measures

Outcome measures
Measure
Tramadol HCl Contramid® Once A Day
n=161 Participants
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=153 Participants
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Patient Diary: Difficulty With Stairs (Between Visit Means) at Week 12
2.97 Units on a scale
Standard Deviation 1.14
3.10 Units on a scale
Standard Deviation 1.16

Adverse Events

Tramadol HCl Contramid® Once A Day

Serious events: 3 serious events
Other events: 159 other events
Deaths: 0 deaths

Tramadol HCl Twice a Day (SR)

Serious events: 8 serious events
Other events: 159 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Tramadol HCl Contramid® Once A Day
n=215 participants at risk
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=215 participants at risk
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Cardiac disorders
Angina Unstable
0.00%
0/215
0.47%
1/215 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Neoplasm NOS
0.00%
0/215
0.47%
1/215 • Number of events 1
Nervous system disorders
Cerebrovascular Disorder NOS
0.00%
0/215
0.47%
1/215 • Number of events 1
General disorders
Chest Pain
0.00%
0/215
0.47%
1/215 • Number of events 1
Hepatobiliary disorders
Cholelithiasis
0.00%
0/215
0.47%
1/215 • Number of events 1
Cardiac disorders
Coronary Artery Insufficiency
0.47%
1/215 • Number of events 1
0.00%
0/215
Vascular disorders
Essential Hypertension
0.47%
1/215 • Number of events 1
0.00%
0/215
Nervous system disorders
Ischaemic Stroke NOS
0.47%
1/215 • Number of events 1
0.00%
0/215
Gastrointestinal disorders
Peritoneal Adhesions
0.00%
0/215
0.47%
1/215 • Number of events 1
Renal and urinary disorders
Renal Colic
0.00%
0/215
0.47%
1/215 • Number of events 1
Injury, poisoning and procedural complications
Tibia Fracture
0.00%
0/215
0.47%
1/215 • Number of events 1

Other adverse events

Other adverse events
Measure
Tramadol HCl Contramid® Once A Day
n=215 participants at risk
The available doses for Tramadol HCl Contramid Once A Day (OAD) were 100 mg, 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Tramadol HCl Twice a Day (SR)
n=215 participants at risk
The available doses for Tramadol HCl Twice a day (SR) were 200 mg, 300 mg or 400 mg daily. Each patient was titrated to his/her optimum dose (based on efficacy and tolerability) and maintained that dose until the end of the study.
Gastrointestinal disorders
Constipation
34.0%
73/215 • Number of events 136
30.2%
65/215 • Number of events 143
Nervous system disorders
Dizziness
23.7%
51/215 • Number of events 85
30.2%
65/215 • Number of events 97
Gastrointestinal disorders
Dry mouth
9.3%
20/215 • Number of events 28
4.7%
10/215 • Number of events 15
Nervous system disorders
Headache
12.6%
27/215 • Number of events 37
17.7%
38/215 • Number of events 54
Gastrointestinal disorders
Nausea
32.6%
70/215 • Number of events 121
34.0%
73/215 • Number of events 134
Nervous system disorders
Somnolence
30.2%
65/215 • Number of events 113
21.4%
46/215 • Number of events 67
Skin and subcutaneous tissue disorders
Sweating increased
7.4%
16/215 • Number of events 17
7.0%
15/215 • Number of events 25
Gastrointestinal disorders
Vomiting
8.4%
18/215 • Number of events 24
14.4%
31/215 • Number of events 34
General disorders
Weakness
11.2%
24/215 • Number of events 33
14.4%
31/215 • Number of events 47

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