Efficacy, safety, and gastrointestinal tolerability of tapentadol ER in a randomized, double-blind, placebo- and active-controlled phase III study of patients with chronic low back pain

Abstract

In this phase III study, 981 patients with moderate-to-severe chronic low back pain were randomized to receive controlled adjustable doses of tapentadol ER (100-250mg), oxycodone HCl CR (20-50mg), or placebo bid for 12 weeks following a 3-week titration period; 965 patients were evaluable for safety and 958 for efficacy. Both tapentadol ER and oxycodone CR significantly (P < 0.001 for both) reduced pain intensity compared with placebo at Week 12 using the last observation carried forward for missing values. The incidences of overall treatment-emergent adverse events (TEAEs) were 84.8% for oxycodone CR, 75.5% for tapentadol ER, and 59.6% for placebo. Gastrointestinal TEAEs were reported by 61.9%, 43.7%, and 26.3% of patients in the oxycodone CR, tapentadol ER, and placebo groups, respectively, including constipation (26.8%, 13.8%, and 5.0%), nausea (34.5%, 20.1%, and 9.1%), and vomiting (19.2%, 9.1%, and 1.6%). The incidences of first onset of vomiting and constipation rose more rapidly throughout the study among patients treated with oxycodone CR than those treated with tapentadol ER. The proportions of patients who discontinued due to overall TEAEs were 31.7% for oxycodone CR, 16.7% for tapentadol ER, and 4.4% for placebo. Gastrointestinal TEAEs were the most common TEAE-related reason for discontinuation in the oxycodone CR group (18.3%); 5.3% and 1.3% of patients in the tapentadol ER and placebo groups, respectively, discontinued due to gastrointestinal TEAEs. Discontinuations due to constipation, nausea, and vomiting, respectively, were 4.3%, 11.3%, and 7.0% for the oxycodone CR group; 1.3%, 1.6%, and 2.5% for the tapentadol ER group; and 0%, 0.3%, and 0% for the placebo group. Tapentadol ER demonstrated effective relief of chronic low back pain and an improved gastrointestinal tolerability profile compared with oxycodone CR as evidenced by the incidences of constipation, nausea, and vomiting. (Study supported by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. and Grünenthal GmbH.)