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

Pain. 2016 Jan;157(1):264-272. doi: 10.1097/j.pain.0000000000000363.


Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-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 μ-opioid receptor activation is a promising target for development of novel analgesics.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Acute Pain / drug therapy*
  • Acute Pain / etiology
  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid / therapeutic use*
  • Double-Blind Method
  • Female
  • Hallux Valgus / surgery
  • Humans
  • Male
  • Middle Aged
  • Morphine / therapeutic use
  • Orthopedic Procedures / adverse effects
  • Receptors, Opioid, mu / agonists*
  • Spiro Compounds / therapeutic use*
  • Thiophenes / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • ((3-methoxythiophen-2-yl)methyl)((2-(9-(pyridin-2-yl)-6-oxaspiro(4.5)decan-9-yl)ethyl))amine
  • Analgesics, Opioid
  • Receptors, Opioid, mu
  • Spiro Compounds
  • Thiophenes
  • Morphine