title: Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial.
abstract: OBJECTIVE
  Painful diabetic peripheral neuropathy (DPN) may not be adequately managed with available therapeutic options. This phase III, randomized-withdrawal, placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release (ER) for relieving painful DPN.
  
  
  METHODS
  Patients (n = 588) with at least a 3-month history of opioid and/or non-opioid analgesic use for DPN, dissatisfaction with current treatment, and an average pain intensity score of at least 5 on an 11-point numerical rating scale (NRS; 0 = 'no pain,' 10 = 'pain as bad as you can imagine') were titrated to an optimal dose of tapentadol ER (100-250 mg bid) during a 3-week open-label phase. Subsequently, patients (n = 395) with at least a 1-point reduction in pain intensity were randomized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase.
  
  
  BACKGROUND
  NCT00455520.
  
  
  METHODS
  The primary efficacy outcome was the change in average pain intensity from randomization, determined by twice-daily NRS measurements. Safety was assessed throughout the study.
  
  
  RESULTS
  The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was -1.3 (95% confidence interval, -1.70 to -0.92; p < 0.001, tapentadol ER vs. placebo). A total of 60.5% (356/588) of patients reported at least a 30% improvement in pain intensity from the start to the end of the open-label titration phase; of the patients who were randomized to tapentadol ER, 53.6% (105/196) reported at least a 30% improvement from pre-titration to week 12 of the double-blind phase. The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea, anxiety, diarrhea, and dizziness. Potential limitations of this study are related to the enriched enrollment randomized-withdrawal trial design, which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase.
  
  
  CONCLUSIONS
  Compared with placebo, tapentadol ER 100-250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain 1 , 2 and was well-tolerated by patients with painful DPN.
authors.affiliation: Cetero Research, San Antonio, TX 78229, USA. slschwartz@dgdclinic.com
authors.forename: Sherwyn
authors.initials: S
authors.lastname: Schwartz
authors.forename: Mila
authors.initials: M
authors.lastname: Etropolski
authors.forename: Douglas Y
authors.initials: DY
authors.lastname: Shapiro
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Robert
authors.initials: R
authors.lastname: Lange
authors.forename: Juergen
authors.initials: J
authors.lastname: Haeussler
authors.forename: Christine
authors.initials: C
authors.lastname: Rauschkolb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D010636:Phenols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D010919:Placebos; D000077432:Tapentadol; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000706:statistics & numerical data
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010636:Phenols; D010919:Placebos; D000077432:Tapentadol