TY - JOUR
T1 - A randomized, phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty
AU - Singla, Neil
AU - Minkowitz, Harold S.
AU - Soergel, David G.
AU - Burt, David A.
AU - Subach, Ruth Ann
AU - Salamea, Monica Y.
AU - Fossler, Michael J.
AU - Skobieranda, Franck
N1 - Funding Information:
This study was supported by Trevena, Inc (King of Prussia, PA, USA). Neil Singla is an employee of Lotus Clinical Research, LLC, contracted by the sponsor to conduct the study; Dr Singla has also received consulting fees from Trevena, Inc. Harold S Minkowitz has received investigator fees and consulting fees from Trevena, Inc, AcelRx, and The Medicines Company. Ruth Ann Subach was an employee of Trevena, Inc, during the conception/conduct of the study and owns Trevena, Inc, stock. David G Soergel, David A Burt, Monica Y Salamea, Michael J Fossler, and Franck Skobieranda are employees of the study’s sponsor, Trevena, Inc. The authors report no other conflicts of interest in this work.
Funding Information:
Medical writing support was provided by Kevin Wang of Xelay Acumen (San Mateo, CA, USA) and Donna McGuire of Engage Scientific Solutions (Philadelphia, PA, USA) and data analytical support by Cory Mekelburg of Xelay Acumen, which were funded by Trevena, Inc (King of Prussia, PA, USA). The results of this study were presented at the American Society of Regional Anesthesia 41st Annual Regional Anesthesiology and Acute Pain Medicine Meeting (March 31 to April 2, 2016, New Orleans, LA, USA).
Publisher Copyright:
© 2017 Singla et al.
PY - 2017/10/6
Y1 - 2017/10/6
N2 - Background: Oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the µ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration). Methods: Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Results: Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively (P=0.0001 and P=0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P<0.0001 versus placebo). A lower prevalence of adverse events (AEs) related to nausea, vomiting, and respiratory function was observed with the oliceridine regimens than with morphine (P<0.05). Other AEs with oliceridine were generally dose-related and similar in nature to those observed with conventional opioids; no serious AEs were reported with oliceridine. Conclusion: These results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine.
AB - Background: Oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the µ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration). Methods: Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Results: Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively (P=0.0001 and P=0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P<0.0001 versus placebo). A lower prevalence of adverse events (AEs) related to nausea, vomiting, and respiratory function was observed with the oliceridine regimens than with morphine (P<0.05). Other AEs with oliceridine were generally dose-related and similar in nature to those observed with conventional opioids; no serious AEs were reported with oliceridine. Conclusion: These results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine.
KW - Acute pain
KW - Analgesic
KW - Biased ligand
KW - Opioid
KW - TRV130
UR - http://www.scopus.com/inward/record.url?scp=85032856816&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032856816&partnerID=8YFLogxK
U2 - 10.2147/JPR.S137952
DO - 10.2147/JPR.S137952
M3 - Article
C2 - 29062240
AN - SCOPUS:85032856816
SN - 1178-7090
VL - 10
SP - 2413
EP - 2424
JO - Journal of Pain Research
JF - Journal of Pain Research
ER -