(773): Efficacy of a single dose of tapentadol HCl for analgesia after third molar surgery

Abstract

Tapentadol HCl is a new dual mode analgesic (μ-agonism and norepinephrine reuptake inhibition). We investigated whether this compound produces high analgesic efficacy with improved tolerability compared to a pure μ-agonist. The efficacy and safety 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 phase II, randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (N= 400) with moderate-to-severe dental pain following mandibular third molar surgical extraction were randomized within 6 hours of surgery. The primary efficacy endpoint, total pain relief over 8 hours after administration of study medication (TOTPAR-8), was measured by assessing pain relief compared with baseline pain on a 5-point verbal rating scale (0= none, 1= a little, 2= some, 3= a lot, 4= complete pain relief). TOTPAR-8 scores were greater for tapentadol HCl 75 mg (P≠ 0.05), 100 mg (P≠ 0.001), and 200 mg (P≠ 0.001) when compared with placebo; mean TOTPAR-8 scores for tapentadol HCl 200 mg and morphine sulfate 60 mg were 15.3 and 13.8, respectively. Total pain relief after 4 hours was higher and onset of action appeared to be more rapid for tapentadol HCl 200 mg than morphine sulfate 60 mg. The mean level of pain relief obtained with morphine sulfate 60 mg was between that achieved with tapentadol HCl 100 mg and 200 mg. The most commonly reported adverse events for tapentadol HCl 200 mg and morphine sulfate 60 mg were dizziness, nausea, vomiting, and somnolence. Most adverse events were considered mild or moderate in intensity. Thus, a single oral dose of tapentadol HCl from 75 to 200 mg is effective and well-tolerated for the relief of moderate-to-severe dental pain following third molar surgery. Tapentadol HCl is a new dual mode analgesic (μ-agonism and norepinephrine reuptake inhibition). We investigated whether this compound produces high analgesic efficacy with improved tolerability compared to a pure μ-agonist. The efficacy and safety 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 phase II, randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (N= 400) with moderate-to-severe dental pain following mandibular third molar surgical extraction were randomized within 6 hours of surgery. The primary efficacy endpoint, total pain relief over 8 hours after administration of study medication (TOTPAR-8), was measured by assessing pain relief compared with baseline pain on a 5-point verbal rating scale (0= none, 1= a little, 2= some, 3= a lot, 4= complete pain relief). TOTPAR-8 scores were greater for tapentadol HCl 75 mg (P≠ 0.05), 100 mg (P≠ 0.001), and 200 mg (P≠ 0.001) when compared with placebo; mean TOTPAR-8 scores for tapentadol HCl 200 mg and morphine sulfate 60 mg were 15.3 and 13.8, respectively. Total pain relief after 4 hours was higher and onset of action appeared to be more rapid for tapentadol HCl 200 mg than morphine sulfate 60 mg. The mean level of pain relief obtained with morphine sulfate 60 mg was between that achieved with tapentadol HCl 100 mg and 200 mg. The most commonly reported adverse events for tapentadol HCl 200 mg and morphine sulfate 60 mg were dizziness, nausea, vomiting, and somnolence. Most adverse events were considered mild or moderate in intensity. Thus, a single oral dose of tapentadol HCl from 75 to 200 mg is effective and well-tolerated for the relief of moderate-to-severe dental pain following third molar surgery.