Tapentadol immediate release compared with oxycodone immediate release for the relief of moderate-to-severe pain in patients with end stage joint disease

Tapentadol is a novel analgesic in a single molecule with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. The efficacy of tapentadol immediate release (IR) was studied in a double-blind, randomized, placebo-controlled, multicenter trial of patients with moderate-to-severe pain from end-stage joint disease. A total of 666 patients, randomized 1:1:1:1, received an oral dose of tapentadol IR 50 mg, tapentadol IR 75 mg, oxycodone IR 10 mg, or placebo (every 4-6 hours, maximum 6 doses/day). Statistically significant improvements in pain intensity compared with placebo as measured by the primary endpoint, the sum of pain intensity difference over 5 days, were demonstrated by tapentadol IR and oxycodone IR treatment groups (P <0.001). Prespecified comparisons of efficacy indicated that both tapentadol IR dosing regimens (50 and 75 mg every 4-6 hours) were non-inferior to oxycodone IR 10 mg. The most common adverse events were nausea, dizziness, and vomiting. Lower incidences of nausea (tapentadol IR, ≤21%; oxycodone IR, 41%), vomiting (tapentadol IR, ≤14%; oxycodone IR, 34%), and constipation (tapentadol IR, ≤7%; oxycodone IR, 26%) were associated with both doses of tapentadol IR treatment, compared with oxycodone IR 10 mg. Subsequent analyses of the odds ratio and 95% confidence intervals (CI) showed that tapentadol IR 50 and 75 mg have significantly lower odds for the incidence of composite nausea/vomiting and constipation compared with oxycodone IR 10 mg (odds ratios [95% CI]: nausea/vomiting—tapentadol IR 50 mg, 0.21 [0.128, 0.339]; tapentadol IR 75 mg, 0.32 [0.204, 0.501]; constipation—tapentadol IR 50 mg, 0.13 [0.057, 0.302]; tapentadol IR 75 mg, 0.20 [0.098, 0.398]). These findings indicate that tapentadol IR 50 and 75 mg were comparable to oxycodone IR 10 mg but with an improved gastrointestinal tolerability. Johnson & Johnson Pharmaceutical Research and Development and Grünenthal GmbH supported this study.