A randomized, phase 2 study investigating TRV130, a biased ligand of the mu-opioid receptor, for the intravenous treatment of acute pain

作者：Viscusi Eugene R; Webster Lynn; Kuss Michael; Daniels Stephen; Bolognese James A; Zuckerman Seth; Soergel David G; Subach Ruth Ann; Cook Emily; Skobieranda Franck^*

来源：Pain, 2016, 157(1): 264-272.

DOI：10.1097/j.pain.0000000000000363

• TRV130
• Acute pain
• Opioid
• Biased ligand
• Bunionectomy

Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the m-opioid receptor that activates G protein signaling with little beta-arrestin recruitment. In this phase 2, randomized, placebo-and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after bunionectomy. We used an adaptive study design in which 144 patients experiencing moderate-to-severe acute pain after bunionectomy were randomized to receive double-blind TRV130, placebo, or morphine in a pilot phase. After pilot phase analysis, 195 patients were randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); placebo; or morphine 4 mg q4h intravenously. The primary end point was the time-weighted average change in numeric rating scale pain intensity over the 48-hour treatment period. Secondary end points included stopwatch and categorical assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean reductions in pain intensity than placebo over 48 hours (P < 0.005). TRV130 at 2 and 3 mg produced significantly greater categorical pain relief than morphine (P < 0.005) after the first dose, with meaningful pain relief occurring in under 5 minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. These results demonstrate that TRV130 rapidly produces profound analgesia in moderate-to-severe acute pain, suggesting that G-protein-biased m-opioid receptor activation is a promising target for development of novel analgesics.

• 出版日期2016-1