Osteoarthritis, Knee, Pain
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety (up to one year) of Tramadol Once-A-Day (OAD) tablets at the highest doses: 200-400 mg
Interventions
DRUGTramadol OAD
DRUGTramadol OAD 100mg
Sponsors
Labopharm Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 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 one year prior to entry into the study. 2. ESR \< 40 mm/hour 3. WOMAC Pain Subscales total score of more than or equal to 150 mm at baseline. 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 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 (BMI more than or equal to 35) (NIH, 2000) 4. Major illness requiring hospitalization during the 3 months before commencement of the screening period. 5. Unwillingness to cease taking medication other than the study medication for arthritic pain, any other concomitant pain, or OA medications. 6. Patients who have previously failed tramadol 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 |
|---|---|---|
| Adverse Events: 12-months Safety Population | 12 months | Spontaneous adverse events were recorded for patients who received the same dose for at least 350 days. A treatment emergent adverse event (TEAE) was associated to the dose level on which a patient was 2 days prior to the TEAE. Only TEAEs which could be associated with the dose level on which the patient was for the longest time were considered. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tramadol OAD 200mg All Patients who Received 1x200 mg Tramadol OAD Tablet daily for at Least 350 days.
OAD = Once-A-Day. | 141 |
| Tramadol OAD 300mg All Patients who Received 1x300 mg Tramadol OAD Tablet daily for at Least 350 days.
OAD = Once-A-Day. | 70 |
| Tramadol OAD 400mg All Patients who Received 1x400 mg Tramadol OAD Tablet daily for at Least 350 days.
OAD = Once-A-Day. | 25 |
| Tramadol OAD 100mg All Patients who Received 1x100 mg Tramadol OAD Tablet daily for at Least 350 days.
OAD = Once-A-Day. | 2 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 8 | 3 | 0 |
Baseline characteristics
| Characteristic | Tramadol OAD 200mg | Tramadol OAD 300mg | Tramadol OAD 400mg | Tramadol OAD 100mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 28 Participants | 9 Participants | 0 Participants | 91 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 42 Participants | 16 Participants | 2 Participants | 147 Participants |
| Age Continuous | 60.1 years STANDARD_DEVIATION 9.3 | 60.5 years STANDARD_DEVIATION 8.8 | 58.5 years STANDARD_DEVIATION 10.8 | 56.0 years STANDARD_DEVIATION 5.7 | 60.0 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 123 Participants | 58 Participants | 21 Participants | 1 Participants | 203 Participants |
| Sex: Female, Male Male | 18 Participants | 12 Participants | 4 Participants | 1 Participants | 35 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 | 74 / 141 | 34 / 70 | 8 / 25 | 1 / 2 |
| serious Total, serious adverse events | 4 / 141 | 1 / 70 | 1 / 25 | 0 / 2 |
Outcome results
Primary
Adverse Events: 12-months Safety Population
Spontaneous adverse events were recorded for patients who received the same dose for at least 350 days. A treatment emergent adverse event (TEAE) was associated to the dose level on which a patient was 2 days prior to the TEAE. Only TEAEs which could be associated with the dose level on which the patient was for the longest time were considered.
Time frame: 12 months
Population: Patients who received the same dose for at least 350 days (12 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tramadol OAD 200mg | Adverse Events: 12-months Safety Population | Constipation | 14 participants |
| Tramadol OAD 200mg | Adverse Events: 12-months Safety Population | Dizziness | 9 participants |
| Tramadol OAD 200mg | Adverse Events: 12-months Safety Population | Nausea | 10 participants |
| Tramadol OAD 200mg | Adverse Events: 12-months Safety Population | Somnolence | 6 participants |
| Tramadol OAD 200mg | Adverse Events: 12-months Safety Population | Headache | 7 participants |
| Tramadol OAD 300mg | Adverse Events: 12-months Safety Population | Somnolence | 2 participants |
| Tramadol OAD 300mg | Adverse Events: 12-months Safety Population | Constipation | 9 participants |
| Tramadol OAD 300mg | Adverse Events: 12-months Safety Population | Dizziness | 0 participants |
| Tramadol OAD 300mg | Adverse Events: 12-months Safety Population | Headache | 5 participants |
| Tramadol OAD 300mg | Adverse Events: 12-months Safety Population | Nausea | 4 participants |
| Tramadol OAD 400mg | Adverse Events: 12-months Safety Population | Headache | 2 participants |
| Tramadol OAD 400mg | Adverse Events: 12-months Safety Population | Nausea | 1 participants |
| Tramadol OAD 400mg | Adverse Events: 12-months Safety Population | Somnolence | 0 participants |
| Tramadol OAD 400mg | Adverse Events: 12-months Safety Population | Dizziness | 0 participants |
| Tramadol OAD 400mg | Adverse Events: 12-months Safety Population | Constipation | 1 participants |