Osteoarthritis, Knee, Pain
Conditions
Brief summary
The purpose of this study is to compare the analgesic efficacy and safety of Tramadol Once a Day 100, 200, 300 mg and Placebo
Interventions
One Tramadol Once A Day tablet at randomized dose daily.
DRUGPlacebo
One Placebo tablet daily.
Sponsors
Labopharm Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Males or Females between the ages of 40-75 with a diagnosis of moderate to severe osteoarthritis of the knee, consistent with the American College of Rheumatology (ACR) Clinical Classification Criteria for Arthritis of the Knee: * Current knee pain * Less than 30 minutes of morning stiffness with or without crepitus on active motion. * Confirmation either by arthroscopy or radiologist's report (X-rays showing osteophytes, joint space narrowing or subchondral bone sclerosis {eburnation}) within five years prior to entry into the study. 2. C-reactive protein (CRP) \< 8 ug/ml (if available at local lab) or erythrocyte sedimentation rate (ESR) \< 40 mm/hr 3. Total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) Pain Subscale Score of \> 150 mm at Baseline corresponding with moderate to severe Osteoarthritis. 4. Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials. 5. Research Ethics Board (REB) approval of the written Informed Consent Form in Spanish or English which was signed and dated by the patient and Investigator, prior to study participation.
Exclusion criteria
1. Known rheumatoid arthritis or any other rheumatoid disease. 2. Secondary arthritis i.e. any of the following: septic arthritis; inflammatory joint disease; gout; pseudogout; Paget's disease; joint fracture; acromegaly; fibromyalgia; Wilson's disease; ochronosis; haemochromatosis; osteochondromatosis; or collagen gene mutations. 3. Evidence of effusion greater than 15 cubic centimetre (cc) upon physical examination of the joint at Baseline (Visit 1). 4. Body Mass Index (BMI) ≥ 38. 5. Major illness, requiring hospitalization during the 3 months before commencement of the screening period. 6. The patient was unwilling to stop taking pain medication (for arthritis or other types of pain) or was unwilling to stop taking other medications for the treatment of osteoarthritis (OA). 7. Previous failure or discontinuation (due to adverse events) of tramadol hydrochloride (HCl) therapy. 8. Treatment within the last 3 weeks with any of the following medications: monoamine oxidase inhibitors; tricyclic antidepressants and other tricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selective serotonin reuptake inhibitors; or any other drug that reduces seizure threshold. 9. Treatment with another investigational agent within the last 30 days. 10. A history of seizure disorder other than Infantile Febrile Seizures. 11. Previous or current opioid dependency. 12. Bowel disease causing malabsorption. 13. Pregnancy or lactating or childbearing potential and unwilling to utilize a medically approved method of contraception during participation in this clinical trial. 14. Significant liver disease, defined as active hepatitis or elevated liver enzymes \>3 times the upper boundary of the normal range. 15. Significant renal disease, defined as creatinine clearance \<30 mL/min as estimated by the method of Levey et al., 1999. 16. Current substance abuse or dependence, other than nicotine. 17. Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates. 18. Any other condition, that, in the opinion of the Investigators, would have adversely affected the patient's ability to complete the study or its measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Rating of Pain for the Study Period (12 Weeks) | 12 weeks | 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. |
| Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12) | Baseline to week 12 | 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 ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions. |
| Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12) | Baseline to week 12 | 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 pain (0mm) to extreme pain (100mm). The WOMAC Physical Function subscale results from the sum of 17 questions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Global Rating of Pain Relief | 12 weeks | 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. |
| Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0, week 3, week 6 | 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. |
| Percentage of Participants Who Dropped Out From Trial by Dropout Reason | 12 weeks | Reasons for withdrawal from the trial were collected and the percentage of participants who dropped out from trial were calculated by dropout reason |
| Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0, week 3, week 6 | 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 pain (0mm) to extreme pain (100mm). |
| Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | 12 weeks | Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1: Tramadol Once A Day 100mg | 110 |
| 2: Tramadol Once A Day 200mg | 113 |
| 3: Tramadol Once A Day 300mg | 115 |
| 4: Placebo | 227 |
| Total | 565 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 21 | 19 | 41 | 10 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 17 | 15 | 13 | 52 |
| Overall Study | Physician Decision | 2 | 12 | 5 | 10 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 2 | 10 |
Baseline characteristics
| Characteristic | 1: Tramadol Once A Day 100mg | 2: Tramadol Once A Day 200mg | 3: Tramadol Once A Day 300mg | 4: Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 41 Participants | 36 Participants | 49 Participants | 88 Participants | 214.0 Participants |
| Age, Categorical Between 18 and 65 years | 69 Participants | 77 Participants | 66 Participants | 139 Participants | 351.0 Participants |
| Age Continuous | 59.8 years STANDARD_DEVIATION 9 | 59.8 years STANDARD_DEVIATION 8.4 | 61.0 years STANDARD_DEVIATION 9.6 | 60.6 years STANDARD_DEVIATION 9.6 | 60.4 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 65 Participants | 64 Participants | 72 Participants | 140 Participants | 341.0 Participants |
| Sex: Female, Male Male | 45 Participants | 49 Participants | 43 Participants | 87 Participants | 224.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 110 | 49 / 113 | 57 / 115 | 38 / 227 |
| serious Total, serious adverse events | 2 / 110 | 1 / 113 | 4 / 115 | 3 / 227 |
Outcome results
Primary
Patient Global Rating of Pain for the Study Period (12 Weeks)
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.
Time frame: 12 weeks
Population: 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). Last Individual value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Very effective | 19 participants |
| 1: Tramadol Once A Day 100mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Ineffective | 39 participants |
| 1: Tramadol Once A Day 100mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Effective | 50 participants |
| 2: Tramadol Once A Day 200mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Very effective | 16 participants |
| 2: Tramadol Once A Day 200mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Ineffective | 37 participants |
| 2: Tramadol Once A Day 200mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Effective | 56 participants |
| 3: Tramadol Once A Day 300mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Ineffective | 31 participants |
| 3: Tramadol Once A Day 300mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Effective | 56 participants |
| 3: Tramadol Once A Day 300mg | Patient Global Rating of Pain for the Study Period (12 Weeks) | Very effective | 26 participants |
| 4: Placebo | Patient Global Rating of Pain for the Study Period (12 Weeks) | Ineffective | 100 participants |
| 4: Placebo | Patient Global Rating of Pain for the Study Period (12 Weeks) | Very effective | 29 participants |
| 4: Placebo | Patient Global Rating of Pain for the Study Period (12 Weeks) | Effective | 94 participants |
Primary
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
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 ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.
Time frame: Baseline to week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12) | 36.3 Percentage difference | Standard Deviation 45.3 |
| 2: Tramadol Once A Day 200mg | Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12) | 36.6 Percentage difference | Standard Deviation 40.9 |
| 3: Tramadol Once A Day 300mg | Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12) | 41.0 Percentage difference | Standard Deviation 44.5 |
| 4: Placebo | Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12) | 38.0 Percentage difference | Standard Deviation 41.7 |
Primary
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
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 pain (0mm) to extreme pain (100mm). The WOMAC Physical Function subscale results from the sum of 17 questions.
Time frame: Baseline to week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12) | 31.9 Percentage difference | Standard Deviation 46 |
| 2: Tramadol Once A Day 200mg | Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12) | 37.0 Percentage difference | Standard Deviation 39.3 |
| 3: Tramadol Once A Day 300mg | Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12) | 37.3 Percentage difference | Standard Deviation 41.7 |
| 4: Placebo | Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12) | 33.7 Percentage difference | Standard Deviation 44.3 |
Secondary
Investigator Global Rating of Pain Relief
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.
Time frame: 12 weeks
Population: 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). Last Individual value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Investigator Global Rating of Pain Relief | Very effective | 20 participants |
| 1: Tramadol Once A Day 100mg | Investigator Global Rating of Pain Relief | Ineffective | 39 participants |
| 1: Tramadol Once A Day 100mg | Investigator Global Rating of Pain Relief | Effective | 49 participants |
| 2: Tramadol Once A Day 200mg | Investigator Global Rating of Pain Relief | Very effective | 14 participants |
| 2: Tramadol Once A Day 200mg | Investigator Global Rating of Pain Relief | Ineffective | 37 participants |
| 2: Tramadol Once A Day 200mg | Investigator Global Rating of Pain Relief | Effective | 58 participants |
| 3: Tramadol Once A Day 300mg | Investigator Global Rating of Pain Relief | Effective | 57 participants |
| 3: Tramadol Once A Day 300mg | Investigator Global Rating of Pain Relief | Very effective | 22 participants |
| 3: Tramadol Once A Day 300mg | Investigator Global Rating of Pain Relief | Ineffective | 32 participants |
| 4: Placebo | Investigator Global Rating of Pain Relief | Very effective | 29 participants |
| 4: Placebo | Investigator Global Rating of Pain Relief | Ineffective | 96 participants |
| 4: Placebo | Investigator Global Rating of Pain Relief | Effective | 98 participants |
Secondary
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at lunchtime (last individual visit) | 40.5 mm | Standard Deviation 29.9 |
| 1: Tramadol Once A Day 100mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain Before next morning dose (last individ visit) | 41.1 mm | Standard Deviation 30.1 |
| 1: Tramadol Once A Day 100mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at bed time (last individual visit) | 41.2 mm | Standard Deviation 30.7 |
| 2: Tramadol Once A Day 200mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at lunchtime (last individual visit) | 38.2 mm | Standard Deviation 29.6 |
| 2: Tramadol Once A Day 200mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at bed time (last individual visit) | 41.1 mm | Standard Deviation 29.9 |
| 2: Tramadol Once A Day 200mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain Before next morning dose (last individ visit) | 42.0 mm | Standard Deviation 29.5 |
| 3: Tramadol Once A Day 300mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain Before next morning dose (last individ visit) | 35.5 mm | Standard Deviation 29.3 |
| 3: Tramadol Once A Day 300mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at bed time (last individual visit) | 37.3 mm | Standard Deviation 30.2 |
| 3: Tramadol Once A Day 300mg | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at lunchtime (last individual visit) | 36.6 mm | Standard Deviation 29.4 |
| 4: Placebo | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain Before next morning dose (last individ visit) | 38.5 mm | Standard Deviation 29.8 |
| 4: Placebo | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at bed time (last individual visit) | 39.7 mm | Standard Deviation 29.4 |
| 4: Placebo | Multiple Dose Effect Using 24-hour VAS Pain Questionnaire | Pain at lunchtime (last individual visit) | 38.5 mm | Standard Deviation 29.5 |
Secondary
Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
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.
Time frame: Week 0, week 3, week 6
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 36.3 Percentage difference | Standard Deviation 40.9 |
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 26.7 Percentage difference | Standard Deviation 36.9 |
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 35.2 Percentage difference | Standard Deviation 40.9 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 36.0 Percentage difference | Standard Deviation 40.3 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 29.0 Percentage difference | Standard Deviation 33.4 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 36.4 Percentage difference | Standard Deviation 39.5 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 33.1 Percentage difference | Standard Deviation 41.4 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 42.3 Percentage difference | Standard Deviation 40.6 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 47.7 Percentage difference | Standard Deviation 42.2 |
| 4: Placebo | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 20.4 Percentage difference | Standard Deviation 35.8 |
| 4: Placebo | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 41.3 Percentage difference | Standard Deviation 39.9 |
| 4: Placebo | Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 35.1 Percentage difference | Standard Deviation 39.4 |
Secondary
Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
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 pain (0mm) to extreme pain (100mm).
Time frame: Week 0, week 3, week 6
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 23.4 Percentage difference | Standard Deviation 37.1 |
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 33.5 Percentage difference | Standard Deviation 39.8 |
| 1: Tramadol Once A Day 100mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 33.3 Percentage difference | Standard Deviation 40.7 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 36.5 Percentage difference | Standard Deviation 34.4 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 37.0 Percentage difference | Standard Deviation 36.8 |
| 2: Tramadol Once A Day 200mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 26.4 Percentage difference | Standard Deviation 30.9 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 47.7 Percentage difference | Standard Deviation 43.8 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 41.0 Percentage difference | Standard Deviation 39.7 |
| 3: Tramadol Once A Day 300mg | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 29.3 Percentage difference | Standard Deviation 37.9 |
| 4: Placebo | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 0 (Visit 2) | 18.5 Percentage difference | Standard Deviation 37.7 |
| 4: Placebo | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 6 (Visit 4) | 38.3 Percentage difference | Standard Deviation 37.8 |
| 4: Placebo | Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4) | Week 3 (Visit 3) | 33.7 Percentage difference | Standard Deviation 38.2 |
Secondary
Percentage of Participants Who Dropped Out From Trial by Dropout Reason
Reasons for withdrawal from the trial were collected and the percentage of participants who dropped out from trial were calculated by dropout reason
Time frame: 12 weeks
Population: Safety population: all randomized patients who received at least one dose of the assigned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Adverse event | 19.1 percentage of participants |
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Patient request | 4.5 percentage of participants |
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Death | 0.9 percentage of participants |
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Investigator initiated discontinuation | 1.8 percentage of participants |
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Administrative | 0 percentage of participants |
| 1: Tramadol Once A Day 100mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Lack of efficacy | 15.5 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Patient request | 6.2 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Lack of efficacy | 13.3 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Investigator initiated discontinuation | 10.6 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Adverse event | 16.8 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Administrative | 0 percentage of participants |
| 2: Tramadol Once A Day 200mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Death | 0 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Lack of efficacy | 11.3 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Patient request | 1.7 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Adverse event | 35.7 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Administrative | 0 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Death | 0 percentage of participants |
| 3: Tramadol Once A Day 300mg | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Investigator initiated discontinuation | 4.3 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Death | 0 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Lack of efficacy | 22.9 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Patient request | 4.4 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Investigator initiated discontinuation | 4.4 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Administrative | 0.4 percentage of participants |
| 4: Placebo | Percentage of Participants Who Dropped Out From Trial by Dropout Reason | Adverse event | 4.4 percentage of participants |