A Comparison of the Analgesic Efficacy and Safety of Once Daily Tramadol HCl / Contramid® Tablets to Twice Daily Tramadol HCl (SR) for the Treatment of Osteoarthritis of the Knee
Condition: Osteoarthritis, Knee; Pain
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Tramadol HCl Contramid® Once A Day; Tramadol HCl Twice a day
Intervention description: The patients orally self-administered the study medication: either 100, 200, 300 or 400 mg Tramadol HCl Contramid® Once A Day. Each patient was titrated to his or her optimum dose (up to a maximum of 400 mg) during the Titration Phase, which lasted between 4 and 12 days. The optimum dose was taken throughout the study.; The patients orally self-administered the study medication: either 200, 300 or 400 mg Tramadol HCl Twice a day. Each patient was titrated to his or her optimum dose (up to a maximum of 400 mg) during the Titration Phase, which lasted between 4 and 12 days. The optimum dose was taken throughout the study.
Intervention MeSH terms: Tramadol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 431.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      A randomised, multi-centre, double-blind, double dummy, two arm parallel design study to
      compare the efficacy, safety, and clinical benefit of the test and reference product after
      treatment for 84 days in patients with osteoarthritis of the knee.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males or Females between the ages of 40 and 75 with a diagnosis of Osteoarthritis (OA)
             of the knee consistent with the American College of Rheumatology (ACR) Clinical
             Classification Criteria for Arthritis of the Knee (Altman, R. et al., 1986):

               -  Knee pain at study enrolment,

               -  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 1 year prior to entry into the study.

          2. ESR < 40 mm/h

          3. Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain Subscales
             total score equal to or more than 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 signed and dated the (IEC) 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) equal to or more than 35 kg/m2] (NIH, 2000)

          4. Major illness that required hospitalisation 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 had previously failed tramadol HCl therapy or those who discontinued
             tramadol HCl due to AEs.

          7. Patients who within the 3 weeks prior to study entry took 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 took another investigational agent within the 30 days prior to study
             entry.

          9. Patients with a history of seizure disorder other than Infantile Febrile Seizures.

         10. Patients who were opioid dependent.

         11. Patients with bowel disease causing malabsorption.

         12. Patients who were pregnant or lactating or patients of child-bearing potential who
             were unwilling to utilise 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, adversely affected the
             patient's ability to complete the study or its measures.