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ABSTRACTObjective:To evaluate the relative efficacy and tolerability of tapentadol immediate release (IR) and oxycodone IR for management of moderate to severe pain following orthopedic surgery (bunionectomy).Methods:Randomized patients (N  901) received oral tapentadol IR 50 or 75 mg, oxycodone HCl IR 10 mg, or placebo every 4–6 h over a 72-h period following surgery. Acetaminophen (≤2 g) was allowed in the first 12 h after the first dose of study drug. In the primary analysis, tapentadol IR (50 and 75 mg) was evaluated for efficacy superior to placebo and non-inferior to oxycodone HCl IR 10 mg (using sum of pain intensity difference [SPID] over 48 h), and tolerability superior to oxycodone IR (using incidence of treatment-emergent adverse events [TEAEs] of nausea and/or vomiting).Results:Statistically significantly higher mean SPID48values were observed with tapentadol IR (50 and 75 mg) and oxycodone HCl IR 10 mg than placebo (all p < 0.001). The efficacy of tapentadol IR 50 mg and 75 mg was non-inferior to oxycodone HCl IR 10 mg. The incidence of TEAEs of nausea and/or vomiting was statistically significantly lower with tapentadol IR 50 mg versus oxycodone IR 10 mg (35 vs. 59; p < 0.001). No statistically significant difference in the incidence of nausea and/or vomiting was observed between tapentadol IR 75 mg and oxycodone IR 10 mg (51 vs. 59; p  0.057). A possible limitation of this study was that the intense dose and patient monitoring may not represent real-world situations and may result in higher incidences of TEAEs than expected in a practice setting; this bias would be similar for all treatment groups.Conclusions:Clinically meaningful and statistically significant improvements were observed with tapentadol IR 50 mg and 75 mg compared with placebo for the relief of moderate-to-severe acute pain after orthopedic surgery. Tapentadol IR 50 mg and 75 mg were non-inferior to oxycodone HCl IR 10 mg for the treatment of acute pain based on the primary efficacy endpoint of SPID48and the pre-specified margin of 48 points. The incidence of nausea and/or vomiting was statistically significantly lower for tapentadol IR 50 mg and numerically lower for tapentadol IR 75 mg than for oxycodone HCl IR 10 mg. [ABSTRACT FROM AUTHOR]

ABSTRACTObjective:Tapentadol is a novel, centrally acting analgesic with two mechanisms of action, μ-opioid receptor agonism and norepinephrine reuptake inhibition, in a single molecule. This phase III, randomized, double-blind, active-controlled study evaluated the tolerability of tapentadol immediate release (IR) and oxycodone IR for low back pain or osteoarthritis pain (hip or knee), using flexible dosing over 90 days.Methods:Patients (N  878) were randomly assigned (4:1 ratio) to receive tapentadol IR (50 or 100 mg, q4-6h, p.o.) or oxycodone IR (10 or 15 mg, q4-6h, p.o.). Tapentadol IR was evaluated for tolerability over 90 days, tolerability relative to oxycodone IR, withdrawal symptoms, and pain intensity. This study was not placebo-controlled, which limited efficacy evaluations.Results:In total, 849 intent-to-treat patients received tapentadol IR (n  679) or oxycodone IR (n  170), and among these, 391 patients (57.6) in the tapentadol IR group and 86 patients (50.6) in the oxycodone IR group completed the study. Gastrointestinal events, including nausea (18.4 vs 29.4), vomiting (16.9 vs 30.0), and constipation (12.8 vs 27.1), were reported by 44.2 of patients receiving tapentadol IR and 63.5 of patients receiving oxycodone IR, respectively. Nervous system events, including dizziness (18.1 vs 17.1), headache (11.5 vs 10.0), and somnolence (10.2 vs 9.4), were reported by 36.7 of patients receiving tapentadol and 37.1 of patients receiving oxycodone, respectively. Odds ratios (tapentadol:oxycodone) showed that the incidences of somnolence and dizziness were similar; however, nausea, vomiting, and constipation were significantly less likely with tapentadol IR compared with oxycodone IR. The pattern of withdrawal symptoms suggests that drug tapering may not be necessary after tapentadol IR treatment of this duration. Pain intensity measurements showed similar efficacy for tapentadol and oxycodone.Conclusion:During this 90-day study, tapentadol IR was associated with improved gastrointestinal tolerability compared with oxycodone IR while providing similar pain relief.Trial registration information:NCT00364546. [ABSTRACT FROM AUTHOR]