Efficacy and safety assessment of a novel once-daily tablet formulation of tramadol a randomised, controlled study versus twice-daily tramadol in patients with osteoarthritis of the knee

摘要

Objective: To compare the 24-hour sustained efficacy and safety of a new tramadol once-daily formulation (tramadol OAD) using Contramid~R control-led-release technology with a marketed twice-daily formulation (tramadol BID). Patients, design and setting: 431 patients with osteoarthritis of the knee were enrolled in this randomised, double-blind, multicentre, parallel study. After titra-tion to optimum dose (range l00-400mg), patients received medication for 12 weeks.Main outcome measures and results: Efficacy evaluations included: Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores (pain, stiffness, physical function and global), daily efficacy ratings (post-dose: tramadol OAD 24 hours; tramadol BID 12 hours), pain ratings over 24 hours, and patient and investigator overall ratings. Non-inferiority was demonstrated for the primary endpoint, mean percentage change in WOMAC pain score from baseline to week 12 (tramadol OAD 58%; tramadol BID 59%) [95% CI -7.67, 3.82]. The median optimum dose received was 200mg (both treatments). In 73% of patients, pain was mild to absent at the end of the dosing interval for both treatments (tramadol OAD 24 hours; tramadol BID 12 hours). Pain ratings over 24 hours were similar between groups, indicating 24-hour sustained efficacy for tramadol OAD. More tramadol BID patients reported dizziness/vertigo (37% vs 26%), vomiting (14% vs 8%) and headache (18% vs 13%) while tramadol OAD patients reported more somnolence (30% vs 21%).Conclusions: This study demonstrated that this novel tramadol OAD formulation provides sustained analgesic efficacy over the entire 24-hour dosing interval and a clinically favourable safety profile, both of which will provide a clear clinical benefit.