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

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; pain DETECT 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 .