Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study.

摘要

OBJECTIVE: To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain. RESEARCH DESIGN: Patients (N = 981) were randomized 1:1:1 to receive tapentadol ER 100 - 250 mg b.i.d., oxycodone HCl controlled release (CR) 20 - 50 mg b.i.d., or placebo over 15 weeks (3-week titration period, 12-week maintenance period). MAIN OUTCOME MEASURES: Efficacy was assessed as change from baseline in average pain intensity (11-point NRS) at week 12 of the maintenance period and throughout the maintenance period; last observation carried forward was used to impute missing pain scores. Adverse events (AEs) were monitored throughout the study. RESULTS: Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 (least squares mean difference vs placebo [95% confidence interval], -0.8 [-1.22, -0.47]; p < 0.001) and throughout the maintenance period (-0.7 [-1.06,-0.35]; p < 0.001). Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 (-0.9 [-1.24,-0.49]; p < 0.001) and throughout the maintenance period (-0.8 [-1.16,-0.46]; p < 0.001). Tapentadol ER was associated with a lower incidence of treatment-emergent AEs (TEAEs) than oxycodone CR. Gastrointestinal TEAEs, including constipation, nausea, and vomiting, were among the most commonly reported TEAEs (placebo, 26.3%; tapentadol ER, 43.7%; oxycodone CR, 61.9%). The odds of experiencing constipation or the composite of nausea and/or vomiting were significantly lower with tapentadol ER than with oxycodone CR (both p < 0.001). CONCLUSIONS: Tapentadol ER (100 - 250 mg b.i.d.) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR (20 - 50 mg b.i.d.).