title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology University Hospital of Schleswig-Holstein, Campus Kiel.
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.affiliation: Pain Center, Berlin, Germany.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Jansen
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology University Hospital of Schleswig-Holstein, Campus Kiel.
authors.forename: Andreas
authors.initials: A
authors.lastname: Binder
authors.affiliation: Clinical University Hospital, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pombo-Suarez
authors.affiliation: Grünenthal Innovations - Global Biometrics, Grünenthal GmbH.
authors.forename: Lieven
authors.initials: L
authors.lastname: Kennes
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Falke
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Steigerwald
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D023381:Endpoint Determination; D005260:Female; D006304:Health Status; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy* / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D010147:Pain Measurement; D010636:Phenols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009292:Narcotic Antagonists; D010636:Phenols; D009270:Naloxone; D010098:Oxycodone; D000077432:Tapentadol
keywords: chronic low back pain; quality of life; safety; tapentadol prolonged release; tolerability