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

Inclusion Criteria:

1. Male or Female patients between the ages of 40-75 with a diagnosis of Osteoarthritisof the knee consistent with the ACR Clinical Classification Criteria for Arthritis ofthe Knee (Altman, R. et al., 1991):

• Current knee pain,

• Less than 30 minutes of morning stiffness with or without crepitus on activemotion.

• Confirmation either by arthroscopy or radiologist's report (X-rays showingosteophytes, 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 theprotocol and complete study-related materials.

5. The Patient has signed and dated the REB approved, written, informed consent prior tostudy participation.

Exclusion Criteria:

1. Known rheumatoid arthritis or any other rheumatoid disease.

2. Secondary arthritis, i.e. any of the following: septic arthritis; inflammatory jointdisease; gout; pseudogout; Paget's disease; joint fracture; acromegaly; fibromyalgia;Wilson's disease; Ochronosis; Haemochromatosis; Osteochondromatosis; heritablearthritic 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 thescreening period.

5. Unwillingness to cease taking medication other than the study medication for arthriticpain, any other concomitant pain, or OA medications.

6. Patients who have previously failed tramadol HCl therapy or those who discontinuedtramadol HCl due to adverse events.

7. Patients who are taking or within the last 3 weeks have taken the followingmedications: monoamine oxidase inhibitors; tricyclic antidepressants and othertricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selectiveserotonin reuptake inhibitors; or other drugs which reduce seizure threshold.

8. Patients who are taking or have taken another investigational agent within the last 30days.

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 areunwilling to utilize a medically approved method of contraception during participationin this clinical trial.

13. Patients with significant liver disease, defined as active hepatitis or elevated liverenzymes >3 times the upper boundary of the normal range.

14. Patients with significant renal disease, defined as creatinine clearance <30 mL/min asestimated 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 affectthe patient's ability to complete the study or its measures.