title: 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.
abstract: OBJECTIVE
  To compare the 24-hour sustained efficacy and safety of a new tramadol once-daily formulation (tramadol OAD) using Contramid((R)) controlled-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 titration to optimum dose (range 100-400mg), patients received medication for 12 weeks.
  
  
  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.
authors.affiliation: General Practice, Montpellier, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Mongin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yakusevich
authors.forename: Adorjan
authors.initials: A
authors.lastname: Köpe
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Shostak
authors.forename: Eduard
authors.initials: E
authors.lastname: Pikhlak
authors.forename: Laszlo
authors.initials: L
authors.lastname: Popdán
authors.forename: Judit
authors.initials: J
authors.lastname: Simon
authors.forename: Catherine
authors.initials: C
authors.lastname: Navarro
authors.forename: Louise
authors.initials: L
authors.lastname: Fortier
authors.forename: Sybil
authors.initials: S
authors.lastname: Robertson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bouchard