Background: Tapentadol is a novel, centrally acting analgesic with a dual mode of action, µ-receptor agonism and noradrenaline reuptake inhibition. The aim of this study was to assess efficacy and tolerability of tapentadol extended release (ER) compared to placebo in patients with moderate-to-severe chronic pain due to osteoarthritis of the knee.

Methods: Patients (N=670) were randomly assigned and titrated to a maintenance dose of either tapentadol ER 100mg, tapentadol ER 200mg, oxycodone controlled release (CR) 20mg, or placebo twice daily. Treatment duration was 28 days. Primary efficacy endpoint was average pain intensity over the preceding 24 hours at the final visit based on a 100-mm VAS. Additional endpoints included a Subject Assessment score (excellent, very good, good, fair, or poor). The study design was approved by an institutional review board at each site and all patients provided written informed consent before their enrollment.

Results: Tapentadol ER 200mg showed a significant difference in average pain intensity compared to placebo (least-squares adjusted mean (±SE) difference from placebo -8.4mm [±3.30]; P=0.021). For Tapentadol 100mg the difference in average pain intensity from placebo was -5.9mm (±3.34, P=0.142), and for oxycodone CR 20mg -5.4mm (±3.22; P=0.091). A considerably higher number of patients rated the treatment with tapentadol ER 200mg “Very good” or “Excellent” compared to placebo (48.8% vs. 29,2%). Tapentadol patients experienced less gastrointestinal and central nervous system disorders compared to patients receiving oxycodone.

Conclusions: Tapentadol ER 200mg was effective in the treatment of moderate-to-severe chronic pain due to osteoarthritis of the knee. The efficacy outcome was similar for tapentadol ER 100mg and oxycodone CR 20mg. Tapentadol appears to have an improved GI and CNS tolerability compared to oxycodone.