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A5037
October 26, 2016
10/26/2016 9:45:00 AM - 10/26/2016 11:15:00 AM
Room W476
Rapid Onset of Pain Relief With Oliceridine (TRV130), a Novel µ-GPS, Versus Morphine
Eugene R. Viscusi, M.D., David Soergel, M.D., Franck Skobieranda, M.D., David Burt, Ph.D., Asokumar Buvanendran, M.D.
Thomas Jefferson University, Bensalem, Pennsylvania, United States
Disclosures:   E.R. Viscusi: F. Funded Research; Self; Trevena, Inc. D. Soergel: A. Salary; Self; Trevena, Inc.. E. Stock Options; Self; Trevena, Inc. F. Skobieranda: A. Salary; Self; Trevena, Inc.. E. Stock Options; Self; Trevena, Inc. D. Burt: A. Salary; Self; Trevena, Inc.. E. Stock Options; Self; Trevena, Inc.. A. Buvanendran: None.
Introduction: Morphine may take up to 30 minutes to produce meaningful analgesia. The slow onset of action of morphine makes it difficult to optimally titrate. Potential consequences include excessive dosing and delayed ORAEs. Conventional opioids, such as morphine, bind to μ receptors and non-selectively activate two intracellular signaling pathways: the G protein pathway, associated with analgesia, and the β-arrestin pathway, associated with opioid-related adverse events (ORAEs) and inhibition of G protein-mediated analgesia. Oliceridine (TRV130) is a novel µ receptor G protein Pathway Selective (µ-GPS) modulator that activates G protein while causing low β-arrestin recruitment to the μ receptor. This novel mechanism of action could lead to a differentiated therapeutic profile of rapid, effective analgesia with improved safety and tolerability. In a separate phase 2 abdominoplasty study, oliceridine demonstrated the potential to produce rapid and predictable analgesia, with a significantly lower prevalence of hypoventilation, nausea, and vomiting than morphine (p<0.05 for each ORAE). Here, we present an analysis of the time to onset of pain relief from a randomized, double-dummy, adaptive phase 2 study in patients experiencing postoperative pain following bunionectomy.

Materials and Methods: Patients (N=333) were randomized to receive double-dummy oliceridine 0.5mg, 1mg, 2mg, 3mg, or 4mg; placebo; or morphine 4mg intravenously. Patients were given two running stopwatches and instructed to stop the first when they felt perceptible pain relief and the second when they experienced meaningful pain relief. Rescue analgesics were available as necessary.

Results: Median time to meaningful pain relief was 125, 9, 4, 3, and 2 minutes with oliceridine 0.5mg, 1mg, 2mg, 3mg, or 4mg, respectively, versus 222 and 27 minutes with placebo and morphine 4mg, respectively. Adverse events (AEs) associated with oliceridine were similar in nature to those observed with conventional opioids. There were no serious AEs reported.

Discussion: In this analysis of a phase 2a/b study of patients with postoperative pain following bunionectomy, patients receiving ≥2mg of oliceridine achieved a significantly faster time to onset of meaningful pain relief compared to patients receiving morphine (p<0.05 vs morphine). These results support that oliceridine may rapidly and effectively manage moderate to severe acute pain compared to morphine. Further studies are warranted to determine if this will improve overall pain relief and reduce ORAEs.
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