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

Curr Med Res Opin. 2017 Aug;33(8):1423-1432. doi: 10.1080/03007995.2017.1335189. Epub 2017 Jun 11.


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; oxycodone CR; pain relief; quality-of-life; tapentadol PR; tolerability.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Chronic Pain / drug therapy*
  • Constipation / chemically induced
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Osteoarthritis, Knee / drug therapy*
  • Oxycodone / administration & dosage*
  • Phenols / administration & dosage*
  • Tapentadol
  • Vomiting / chemically induced


  • Delayed-Action Preparations
  • Phenols
  • Oxycodone
  • Tapentadol