A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol OAD Tablets to Twice Daily Tramadol BID for the Treatment of Osteoarthritis of the Knee (Extension Protocol) and Open Label Safety Follow-Up
Condition: Pain; Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Tramadol OAD; Tramadol OAD; Tramadol OAD; Tramadol OAD 100mg
Intervention MeSH terms: Tramadol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 238.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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.