PMID- 31814753 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220411 IS - 1178-7090 (Print) IS - 1178-7090 (Electronic) IS - 1178-7090 (Linking) VI - 12 DP - 2019 TI - ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The micro-Opioid Receptor, In Patients With Moderate To Severe Acute Pain Requiring Parenteral Opioid Therapy. PG - 3113-3126 LID - 10.2147/JPR.S217563 [doi] AB - BACKGROUND: Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of beta-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the micro-opioid receptor with less recruitment of beta-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions. METHODS: Adult patients with a score >/=4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures. RESULTS: A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% >/=65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 +/- 2.3 at 30 mins from a score of 6.3 +/- 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients. CONCLUSION: Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied. CLINICALTRIALSGOV IDENTIFIER: NCT02656875. CI - (c) 2019 Bergese et al. FAU - Bergese, Sergio D AU - Bergese SD AUID- ORCID: 0000-0001-5641-5908 AD - School of Medicine, Stony Brook University, Stony Brook, NY, USA. FAU - Brzezinski, Marek AU - Brzezinski M AUID- ORCID: 0000-0002-7412-4247 AD - School of Medicine, University of California San Francisco, VA Medical Center, San Francisco, CA, USA. FAU - Hammer, Gregory B AU - Hammer GB AUID- ORCID: 0000-0002-7193-3938 AD - Stanford University School of Medicine, Stanford, CA, USA. FAU - Beard, Timothy L AU - Beard TL AD - Clinical Research, Summit Medical Group/Bend Memorial Clinic, Bend, OR, USA. FAU - Pan, Peter H AU - Pan PH AD - Wake Forest School of Medicine, Winston-Salem, NC, USA. FAU - Mace, Sharon E AU - Mace SE AD - Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA. FAU - Berkowitz, Richard D AU - Berkowitz RD AD - Phoenix Clinical Research, Tamarac, FL, USA. FAU - Cochrane, Kristina AU - Cochrane K AD - Trevena, Inc., Chesterbrook, PA, USA. FAU - Wase, Linda AU - Wase L AUID- ORCID: 0000-0003-0124-3744 AD - Trevena, Inc., Chesterbrook, PA, USA. FAU - Minkowitz, Harold S AU - Minkowitz HS AUID- ORCID: 0000-0002-6728-5712 AD - HD Research Corporation, Houston, TX, USA. FAU - Habib, Ashraf S AU - Habib AS AD - Duke University Medical Center, Durham, NC, USA. LA - eng SI - ClinicalTrials.gov/NCT02656875 PT - Journal Article DEP - 20191114 PL - New Zealand TA - J Pain Res JT - Journal of pain research JID - 101540514 PMC - PMC6861532 OTO - NOTNLM OT - acute pain OT - analgesia OT - clinical trial OT - patient-controlled COIS- Sergio D Bergese, Marek Brzezinski, Gregory B Hammer, Timothy L Beard, Peter H Pan, Sharon E Mace and Richard D Berkowitz received research grant funding for the ATHENA study and have served as a consultant for Trevena, Inc. At the time of conduct of the study, and submission of the manuscript to the journal, Sergio D Bergese was affiliated with the Ohio State University Wexner Medical Center; that was the participating site for the trial. Harold S Minkowitz is a consultant for Trevena, Inc. and received research funding from Trevena, Inc., AcelRx Pharmaceuticals, Cara Therapeutics, Durect, Heron Therapeutics, Innocoll, and Pacira Pharmaceuticals. Linda Wase and Kristina Cochrane are full-time employees of Trevena, Inc. and own stock in Trevena, Inc. Ashraf S Habib has received research support from Trevena, Inc., Pacira Pharmaceuticals, BioQ Pharma and Halyard Health and is a consultant for Trevena, Inc. The authors report no other conflicts of interest in this work. EDAT- 2019/12/10 06:00 MHDA- 2019/12/10 06:01 PMCR- 2019/11/14 CRDT- 2019/12/10 06:00 PHST- 2019/05/30 00:00 [received] PHST- 2019/10/19 00:00 [accepted] PHST- 2019/12/10 06:00 [entrez] PHST- 2019/12/10 06:00 [pubmed] PHST- 2019/12/10 06:01 [medline] PHST- 2019/11/14 00:00 [pmc-release] AID - 217563 [pii] AID - 10.2147/JPR.S217563 [doi] PST - epublish SO - J Pain Res. 2019 Nov 14;12:3113-3126. doi: 10.2147/JPR.S217563. eCollection 2019.