(312/776): Efficacy and safety of tapentadol HCl in patients with pain after bunionectomy

Abstract

Bunionectomy is an excellent orthopedic model for assessing the efficacy of potent analgesics. Tapentadol HCl is a new dual mode analgesic (μ-agonism and inhibition of norepinephrine reuptake). We evaluated whether this compound produces high analgesic efficacy with improved tolerability compared to a pure μ-agonist. The efficacy and tolerability of single oral doses of tapentadol HCl (25, 50, 75, 100, or 200 mg), morphine sulfate (60 mg), ibuprofen (400 mg), and placebo were evaluated in a double-blind, randomized, phase II clinical trial of patients with moderate-to-severe pain following standardized bunionectomy. Patients (N= 517, ages 18 to 65 years) were randomized to 1 of 8 treatment groups within 6 hours of surgery. The primary efficacy endpoint was total pain relief over 8 hours after administration of study medication (TOTPAR-8). Tapentadol HCl ≥50 mg yielded dose-dependently and significantly higher mean TOTPAR-8 scores versus placebo (P ≤0.05; range, <0.001-0.014). TOTPAR-8 scores for tapentadol HCl 200 mg were numerically but not significantly higher than those for morphine sulfate 60 mg (8.1 vs 6.7, respectively). However, for the exploratory endpoint of mean total pain relief over 4 hours (TOTPAR-4), tapentadol HCl 200 mg was significantly higher (P ≤0.05) compared with morphine sulfate 60 mg. For the most common opioid-related side effects reported ≥25% incidence), compared to morphine sulfate 60 mg, tapentadol HCl 200 mg was associated with lower rates of nausea (57.1% vs 40.9%, respectively) and dizziness (36.5% vs 25.8%, respectively) and similar rates of somnolence (41.3% vs 37.9%, respectively) and vomiting (36.5% vs 37.9%, respectively). We conclude that single oral doses of tapentadol HCl from 50 to 200 mg reduced moderate-to-severe pain after bunionectomy in a dose related manner and were well tolerated. Compared to oral morphine, this novel dual mode analgesic appears to show an improved tolerability profile.