Objective: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain.
Methods: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.
Main outcome measures: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity.
Results: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall (p <or= 0.021) and for each dose (p <or= 0.050). However, the protocol-specified decision rule for the 3 co-primary endpoints was not satisfied because the overall comparison of subject global assessment of disease activity was not statistically significant (p = 0.079). All doses of tramadol ER once daily were more effective than placebo (p <or= 0.050) for WOMAC Osteoarthritis Index joint stiffness subscale, WOMAC Osteoarthritis Index composite score, pain intensity of the index joint, and daily pain intensity scores. Tramadol ER 200 and 300 mg were significantly more effective than placebo (p <or= 0.050) for subject global assessment of disease activity and pain intensity of non-index joints. Adverse events (e.g., constipation, dizziness, nausea, somnolence, headache) occurred most often with tramadol ER 400 mg.
Conclusions: Tramadol ER 100-300 mg once daily was associated with significant improvement in pain intensity and physical function, and was well tolerated, despite the use of a fixed-dose study design not reflective of usual clinical practice. Tramadol ER is a useful treatment option for patients with osteoarthritis pain.