Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study

Pain Pract. 2016 Jun;16(5):580-99. doi: 10.1111/papr.12308. Epub 2015 Jun 12.

Abstract

Objective: To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component.

Methods: Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) 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. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses).

Results: For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005).

Conclusions: The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component.

Keywords: RCT; chronic low back pain; effectiveness; neuropathic pain; randomized controlled trial; tapentadol prolonged release.

Publication types

  • Clinical Trial, Phase III
  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / therapeutic use*
  • Delayed-Action Preparations
  • Endpoint Determination
  • Female
  • Humans
  • Low Back Pain / drug therapy*
  • Male
  • Middle Aged
  • Naloxone / administration & dosage*
  • Naloxone / therapeutic use*
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / therapeutic use*
  • Neuralgia / drug therapy*
  • Oxycodone / administration & dosage*
  • Oxycodone / therapeutic use*
  • Pain Measurement
  • Phenols / administration & dosage*
  • Phenols / therapeutic use*
  • Tapentadol

Substances

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