A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy

Diabetes Care. 2014 Aug;37(8):2302-9. doi: 10.2337/dc13-2291. Epub 2014 May 21.


Objective: This study evaluated the efficacy and tolerability of tapentadol extended release (ER) for the management of chronic pain associated with diabetic peripheral neuropathy (DPN).

Research design and methods: Adults with moderate to severe DPN pain were titrated to tapentadol ER 100-250 mg bid during a 3-week open-label period; patients with ≥1-point reduction in pain intensity (11-point numerical rating scale) at end of titration were randomized to receive placebo or tapentadol ER (optimal dose from titration) for 12 weeks (double-blind, fixed-dose maintenance phase). The primary end point was mean change in average pain intensity from the start to week 12 (last observation carried forward [LOCF]) of the double-blind maintenance phase.

Results: A total of 358 patients completed the titration period; 318 patients (placebo, n = 152; tapentadol ER, n = 166) were randomized and received one or more doses of double-blind study medication. Mean (SD) pain intensity (observed case) was 7.33 (1.30) at the start and 4.16 (2.12) at week 3 of the open-label titration period (mean [SD] change, -3.22 [1.97]). The mean (SD) change in pain intensity (LOCF) from start of double-blind treatment to week 12 was as follows: placebo, 1.30 (2.43); tapentadol ER, 0.28 (2.04; least squares mean difference, -0.95 [95% CI -1.42 to -0.49]; P < 0.001). Treatment-emergent adverse events (≥10%) in the tapentadol ER group during the double-blind maintenance phase were nausea (21.1%) and vomiting (12.7%).

Conclusions: Tapentadol ER (100-250 mg bid) was effective and well tolerated for the management of moderate to severe chronic pain associated with DPN.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Pain / drug therapy*
  • Delayed-Action Preparations
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / epidemiology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / epidemiology
  • Phenols / therapeutic use*
  • Placebos
  • Tapentadol
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / epidemiology
  • Withholding Treatment
  • Young Adult


  • Delayed-Action Preparations
  • Phenols
  • Placebos
  • Tapentadol