A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee (With 7-Day Follow-up)

Inclusion criteria

• Males or Females between the ages of 40-75 with a diagnosis of moderate to severe osteoarthritis of the knee, consistent with the 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.
• CRP < 8 ug/mL (if available at local lab) or ESR < 40 mm/hr.
• Total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) Pain Subscale Score of > 150 mm at Baseline corresponding with moderate to severe Osteoarthritis.
• Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials.
• 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

• Known rheumatoid arthritis or any other rheumatoid disease.
• 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.
• Evidence of effusion greater than 15 cc upon physical examination of the joint at Baseline (Visit 1).
• BMI greater than or equal to 38.
• Major illness, requiring hospitalization during the 3 months before commencement of the screening period.
• Unwillingness to stop taking pain medication (for arthritis or other types of pain) or was unwilling to stop taking other medications for the treatment of OA.
• Previous failure or discontinuation (due to adverse events) of tramadol HCl therapy.
• 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.
• Treatment with another investigational agent within the last 30 days.
• A history of seizure disorder other than Infantile Febrile Seizures.
• Previous or current opioid dependency.
• Bowel disease causing malabsorption.
• Pregnancy or lactating or childbearing potential and unwilling to utilize a medically approved method of contraception during participation in this clinical trial.
• Significant liver disease, defined as active hepatitis or elevated liver enzymes >3 times the upper boundary of the normal range.
• Significant renal disease, defined as creatinine clearance <30 mL/min as estimated by the method of Levey et al., 1999.
• Current substance abuse or dependence, other than nicotine.
• Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates.
• 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.