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

Objective To evaluate the effectiveness of tapentadolprolonged release (PR) vs. oxycodone/naloxonePR in non–opioid-pretreated patients with severe chronic low back pain with a neuropathic paincomponent. Methods Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) 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. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadolPR minus oxycodone/naloxonePR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). Results For the primary effectiveness endpoint, tapentadolPR was noninferior to oxycodone/naloxonePR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadolPR vs. oxycodone/naloxonePR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic PainSymptom Inventory scores were significantly greater with tapentadolPR vs. oxycodone/naloxonePR (all P ≤ 0.005). Conclusions The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadolPR vs. oxycodone/naloxonePR. The effectiveness of tapentadolPR was superior to that of oxycodone/naloxonePR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). TapentadolPR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxonePR and with a significantly better gastrointestinal tolerability profile. TapentadolPR may be considered a first-line option for managing severe chronic low back pain with a neuropathic paincomponent.