1028 patients with pain due to osteoarthritis of the knee were enrolled in this multi-center, randomized, double-blind parallel study designed to assess the analgesic efficacy and safety of Tramadol Contramid^® OAD versus placebo.

This study consisted of a Tramadol Contramid^® OAD open-label phase followed by a double-blind phase. A total of 646 patients were randomized to double-blind treatment with placebo or Tramadol Contramid^® OAD. The dose was then titrated to 300 mg and could be decreased to 200 mg if 300 mg was not tolerated. The optimal dose was then maintained for a period of 12 weeks. The protocol was approved by a properly constituted investigational review board.

The absolute mean improvement in Pain Intensity Numerical Rating Scale (PI-NRS) throughout the study was significantly greater for Tramadol Contramid^® OAD compared to the placebo (p < 0.0001), based on a time-weighted analysis. A responder analysis demonstrated that a significantly greater percentage of patients in the active treatment arm achieved a reduction in the PI-NRS score from baseline to the end of the study (p = 0.035 for a reduction of ≥2 points). A greater percentage of respondents in the Tramadol Contramid^® OAD group indicated improvement on both the Patient and Physician Global Impressions of Change (p = 0.0002 and p = 0.0042, respectively) compared the placebo group. Both the 200 mg and 300 mg doses contributed to the improvement in PI-NRS scores associated with Tramadol Contramid^® OAD versus placebo. Consistent with the commonly reported side effects of tramadol, the most frequent adverse events during the double-blind maintenance phase were nausea (15%), constipation (14%), dizziness/vertigo (10%), and somnolence (7%), the majority of which were mild to moderate in intensity.

These results support the use of Tramadol Contramid^® OAD given once daily as an efficacious and safe treatment for pain due to osteoarthritis.