Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial

Pain Pract. 2016 Jun;16(5):600-19. doi: 10.1111/papr.12361. Epub 2015 Nov 11.

Abstract

Objective: To evaluate tolerability, safety, and quality-of-life outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. oxycodone/naloxone PR.

Methods: Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint.

Results: For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus oxycodone/naloxone PR for the PAC-SYM total score was [-0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (P ≤ 0.024).

Conclusions: Tapentadol PR had a minimal impact on bowel function (noninferior to oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. oxycodone/naloxone PR.

Keywords: chronic low back pain; quality of life; safety; tapentadol prolonged release; tolerability.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Combinations
  • Endpoint Determination
  • Female
  • Health Status
  • Humans
  • Low Back Pain / drug therapy*
  • Low Back Pain / psychology*
  • Male
  • Middle Aged
  • Naloxone / administration & dosage*
  • Naloxone / adverse effects
  • Naloxone / therapeutic use*
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / therapeutic use*
  • Neuralgia / drug therapy*
  • Oxycodone / administration & dosage*
  • Oxycodone / adverse effects
  • Oxycodone / therapeutic use*
  • Pain Measurement
  • Phenols / administration & dosage*
  • Phenols / adverse effects
  • Phenols / therapeutic use*
  • Quality of Life*
  • Tapentadol

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Drug Combinations
  • Narcotic Antagonists
  • Phenols
  • Naloxone
  • Oxycodone
  • Tapentadol