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 tapentadolPR vs. oxycodone/naloxonePR. Methods Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadolPR 50 mg or oxycodone/naloxonePR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadolPR 250 mg, or oxycodone/naloxonePR 40 mg/20 mg plus oxycodonePR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of ConstipationSymptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. Results For the primary tolerability-relatedendpoint, the 97.5% exact repeated confidence interval for tapentadolPR minus oxycodone/naloxonePR for the PAC-SYM total score was [−0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipationand vomiting were significantly lower with tapentadolPR than oxycodone/naloxonePR (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 tapentadolPR vs. oxycodone/naloxonePR (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 tapentadolPR vs. oxycodone/naloxonePR (P ≤ 0.024). Conclusions TapentadolPR had a minimal impact on bowel function (noninferior to oxycodone/naloxonePR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipationand vomiting and significant improvements in quality-of-life measures vs. oxycodone/naloxonePR.