Osteoarthritis, Knee
Conditions
Keywords
Moderate to severe symptomatic osteoarthritis of the knee
Brief summary
The purpose of this study is to collect information regarding the long-term (6 and 12 months) safety of Tramadol HCl Once-A-Day(OAD) 300 mg.
Interventions
Sponsors
Labopharm Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or Female patients between the ages of 40-75 with a diagnosis of Osteoarthritis of the knee consistent with the American College of Rheumatology (ACR) Clinical Classification Criteria for Arthritis of the Knee (Altman, R. et al., 1991): * 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 two years prior to entry into the study. 2. Erythrocyte Sedimentation Rate (ESR) \< 40 mm/hour. 3. Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain Subscale total score of \>= 150 mm at baseline. (5 questions/100 mm scale each with an averaged response of 30 mm or higher per question). 4. Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials. 5. The Patient has signed and dated the Research Ethics Board (REB) approved, written, informed consent 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; heritable arthritic disorders; or collagen gene mutations. 3. Obesity Class II (Body Mass Index (BMI) \>= 35) (National Institutes of Health (NIH), 2000). 4. Major illness requiring hospitalization during the 3 months before commencement of the screening period. 5. Patients who are unwilling to stop taking pain medication other than the study medication (for arthritis or other types of pain) or are unwilling to stop taking other medications for the treatment of osteoarthritis (OA). 6. Patients who have previously failed tramadol hydrochloride (HCl) therapy or those who discontinued tramadol HCl due to adverse events. 7. Patients who are taking or within the last 3 weeks have taken the following medications: monoamine oxidase inhibitors; tricyclic antidepressants and other tricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selective serotonin reuptake inhibitors; or other drugs which reduce seizure threshold. 8. Patients who are taking or have taken another investigational agent within the last 30 days. 9. Patients with a history of seizure disorder other than Infantile Febrile Seizures. 10. Patients who are opioid dependent. 11. Patients with bowel disease causing malabsorption. 12. Patients who are pregnant or lactating or patients of child-bearing potential who are unwilling to utilize a medically approved method of contraception during participation in this clinical trial. 13. Patients with significant liver disease, defined as active hepatitis or elevated liver enzymes \>3 times the upper boundary of the normal range. 14. Patients with significant renal disease, defined as creatinine clearance \<30 mL/min as estimated by the method of Levey et al., 1999. 15. Current substance abuse or dependence, other than nicotine. 16. Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates. 17. Any other condition that, in the opinion of the investigators, would adversely affect the patient's ability to complete the study or its measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation | 6 months and 12 months | Spontaneous reports of adverse events were recorded for the entire study population, the 6-months safety population and the 12-months safety population |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 300 mg Tramadol HCl OAD | 392 |
| Total | 392 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintenance Phase I | Adverse Event | 73 |
| Maintenance Phase I | Lack of Efficacy | 4 |
| Maintenance Phase I | Physician Decision | 10 |
| Maintenance Phase I | Withdrawal by Subject | 11 |
| Maintenance Phase II | Adverse Event | 6 |
| Maintenance Phase II | Lack of Efficacy | 1 |
| Maintenance Phase II | Physician Decision | 2 |
| Maintenance Phase II | Withdrawal by Subject | 1 |
| Titration | Adverse Event | 18 |
| Titration | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | 300 mg Tramadol HCl OAD |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 163 Participants |
| Age, Categorical Between 18 and 65 years | 229 Participants |
| Age Continuous | 61.4 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 333 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 321 / 392 | 169 / 275 | 101 / 168 |
| serious Total, serious adverse events | 9 / 392 | 1 / 275 | 0 / 168 |
Outcome results
Primary
Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation
Spontaneous reports of adverse events were recorded for the entire study population, the 6-months safety population and the 12-months safety population
Time frame: 6 months and 12 months
Population: All patients having taken 1 dose of 300 mg Tramadol HCl OAD at a minimum are being assessed for adverse event occurence for up to 12 months.~6-months safety: patients who completed at least 175 days on treatment.~12-months safety: patients who completed at least 350 days on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients With 1 Dose of 300 mg Tramadol HCl OAD Minimum | Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation | 346 participants |
| 6-months Safety | Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation | 188 participants |
| 12-months Safety | Number of Patients Having Experienced an Adverse Event During the 6-12 Month Open-Label Safety Participation | 121 participants |