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

Abstract

Objective: To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain.

Methods: Patients (n = 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.

Results: 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]; p = 0.152 and 0.2 [95% CI = –0.16–0.54]; p = 0.279, respectively) and over the maintenance period (LS mean difference = –0.2 [95% CI = –0.55–0.07]; p = 0.135 and 0.1 [95% CI = –0.18–0.44]; p = 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 (p < 0.001).

Conclusions: 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.

Keywords:

• Chronic osteoarthritis pain
• tapentadol PR
• oxycodone CR
• pain relief
• quality-of-life
• tolerability

Transparency

Declaration of funding

The study was funded by Johnson & Johnson, Pharmaceutical Research & Development, L.L.C., and Global Development, Grünenthal GmbH, Aachen, Germany.

Declaration of financial/other relationships

AS received speaking and/or consultancy fees from Mundipharma, Grünenthal, Astellas, and Teva. BL is an employee of Grünenthal GmbH. AS was an employee of Grünenthal GmbH at the time this study was conducted. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Writing assistance was provided by Elke Grosselindemann and Birgit Brett and was paid for by Grünenthal GmbH, Germany.