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

ER Viscusi, L Webster, M Kuss, S Daniels… - Pain, 2016 - journals.lww.com
ER Viscusi, L Webster, M Kuss, S Daniels, JA Bolognese, S Zuckerman, DG Soergel…
Pain, 2016journals.lww.com
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 b-arrestin recruitment. In this phase 2, randomized, placebo-and activecontrolled
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 …
Abstract
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 b-arrestin recruitment. In this phase 2, randomized, placebo-and activecontrolled 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.
Lippincott Williams & Wilkins