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Sergio D Bergese,1 Marek Brzezinski,2 Gregory B Hammer,3 Timothy L Beard,4 Peter H Pan,5 Sharon E Mace,6 Richard D Berkowitz,7 Kristina Cochrane,8 Linda Wase,8 Harold S Minkowitz,9 Ashraf S Habib10 1School of Medicine, Stony Brook University, Stony Brook, NY, USA; 2School of Medicine, University of California San Francisco, VA Medical Center, San Francisco, CA, USA; 3Stanford University School of Medicine, Stanford, CA, USA; 4Clinical Research, Summit Medical Group/Bend Memorial Clinic, Bend, OR, USA; 5Wake Forest School of Medicine, Winston-Salem, NC, USA; 6Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA; 7Phoenix Clinical Research, Tamarac, FL, USA; 8Trevena, Inc., Chesterbrook, PA, USA; 9HD Research Corporation, Houston, TX, USA; 10Duke University Medical Center, Durham, NC, USACorrespondence: Sergio D BergeseSchool of Medicine, Stony Brook University, Health Sciences Center, Level 4, Room 060, Stony Brook, NY 11794, USATel +1 631-444-2979Fax +1-631-444-2907Email Sergio.Bergese@stonybrookmedicine.eduBackground: 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 β-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 μ-opioid receptor with less recruitment of β-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.ClinicalTrials.gov identifier: NCT02656875.Keywords: acute pain, analgesia, patient-controlled, clinical trial |
