Tapentadol prolonged-release for moderate-to-severe chronic osteoarthritis knee pain: a double-blind, randomized, placebo- and oxycodone controlled release-controlled study

<p><b>Objective:</b> To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain.</p> <p><b>Methods:</b> Patients (<i>n</i> = 990) were randomized (1:1:1) to tapentadol PR, oxycodone controlled release (CR; reference compound for assay sensitivity), or placebo for a double-blind 3-week titration and 12-week maintenance period. Primary efficacy end-points were change from baseline in average pain intensity at week 12 of maintenance (US end-point) and over the entire maintenance period (non-US end-point) with “last observation carried forward” as imputation method for missing scores.</p> <p><b>Results:</b> Both primary end-points were not significantly different for tapentadol PR nor for oxycodone CR vs placebo at week 12 (least squares [LS] mean difference = –0.3 [95% CI = –0.61–0.09]; <i>p</i> = 0.152 and 0.2 [95% CI = –0.16–0.54]; <i>p</i> = 0.279, respectively) and over the maintenance period (LS mean difference = –0.2 [95% CI = –0.55–0.07]; <i>p</i> = 0.135 and 0.1 [95% CI = –0.18–0.44]; <i>p</i> = 0.421, respectively). Considerably more patients receiving tapentadol PR than oxycodone CR completed the trial (58.3% vs 36.6%). This is consistent with better results with tapentadol PR on the overall health status (PGIC) compared to oxycodone CR. Indeed, respectively, 56% and 42.5% rated at least “much improved” at the end of treatment. Incidences of gastrointestinal adverse events were higher for both active treatments compared to placebo. Tapentadol PR was associated with a better gastrointestinal tolerability profile with incidences of constipation (17.9% vs 35%) and of the composite of nausea and/or vomiting (23.8% vs 46.8%) significantly lower vs oxycodone CR (<i>p</i> < 0.001).</p> <p><b>Conclusions:</b> The study did not demonstrate assay sensitivity. The finding that both primary end-points for tapentadol PR were not met can, thus, not be interpreted. Tapentadol PR was better tolerated than oxycodone CR, largely due to fewer gastrointestinal side-effects.</p