{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:35:36Z","timestamp":1791999336124,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The clinical utility of conventional IV opioids is limited by the occurrence of opioid\u2010related adverse events. Oliceridine is a novel G protein\u2013biased \u03bc\u2010opioid receptor agonist designed to provide analgesia with an improved safety and tolerability profile. This phase\n                      <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>\n                      , double\u2010blind, randomized trial (\n                      <jats:styled-content style=\"fixed-case\">APOLLO<\/jats:styled-content>\n                      \u20102 [\n                      <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n                      02820324]) evaluated the efficacy and safety of oliceridine for acute pain following abdominoplasty.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients received a loading dose of either placebo, oliceridine (1.5\u00a0mg), or morphine (4\u00a0mg), followed by demand doses via patient\u2010controlled analgesia (0.1, 0.35, or 0.5\u00a0mg oliceridine; 1\u00a0mg morphine; or placebo) with a 6\u2010minute lockout interval. The primary endpoint was the proportion of treatment responders over 24\u00a0hours for oliceridine regimens compared to placebo. Secondary outcomes included a predefined composite measure of respiratory safety burden (\n                      <jats:styled-content style=\"fixed-case\">RSB<\/jats:styled-content>\n                      , representing the cumulative duration of respiratory safety events) and the proportion of treatment responders vs. morphine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 401 patients were treated with\u00a0study medication. Effective analgesia was observed for all oliceridine regimens, with responder rates of 61.0%, 76.3%, and 70.0% for the 0.1\u2010, 0.35\u2010, and 0.5\u2010mg regimens, respectively, compared with 45.7% for placebo (all\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.05) and 78.3% for morphine. Oliceridine 0.35\u2010 and 0.5\u2010mg demand dose regimens were equi\u2010analgesic to morphine using a noninferiority analysis.\n                      <jats:styled-content style=\"fixed-case\">RSB<\/jats:styled-content>\n                      showed a dose\u2010dependent increase across oliceridine regimens (mean hours [\n                      <jats:styled-content style=\"fixed-case\">standard deviation<\/jats:styled-content>\n                      ], 0.1\u00a0mg: 0.43 [1.56]; 0.35\u00a0mg: 1.48 [3.83]; 0.5\u00a0mg: 1.59 [4.26]; all comparisons not significant at\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &gt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.05 vs. placebo: 0.60 [2.82]). The\n                      <jats:styled-content style=\"fixed-case\">RSB<\/jats:styled-content>\n                      measure for morphine was 1.72 (3.86) (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.05 vs. placebo). Gastrointestinal adverse events increased in a dose\u2010dependent manner across oliceridine demand dose regimens (0.1\u00a0mg: 49.4%; 0.35\u00a0mg: 65.8%; 0.5\u00a0mg: 78.8%; vs. placebo: 47.0%; and morphine: 79.3%). In comparison to morphine, the proportion of patients experiencing nausea or vomiting was lower with the 2 equi\u2010analgesic dose regimens of 0.35 and 0.5\u00a0mg oliceridine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Oliceridine is a safe and effective IV analgesic for the relief of moderate to severe acute postoperative pain in patients undergoing abdominoplasty. Since the low\u2010dose regimen of 0.1\u00a0mg oliceridine was superior to placebo but not as effective as the morphine regimen, safety comparisons to morphine are relevant only to the 2 equi\u2010analgesic dose groups of 0.35 and 0.5\u00a0mg, which showed a favorable safety and tolerability profile regarding respiratory and gastrointestinal adverse effects compared to morphine. These findings support that oliceridine may provide a new treatment option for patients with moderate to severe acute pain where an\n                      <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>\n                      opioid is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/papr.12801","type":"journal-article","created":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T08:02:11Z","timestamp":1559635331000},"page":"715-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":175,"title":["APOLLO\u20102: A Randomized, Placebo and Active\u2010Controlled Phase\n                    <scp>III<\/scp>\n                    Study Investigating Oliceridine (\n                    <scp>TRV<\/scp>\n                    130), a G Protein\u2013Biased Ligand at the \u03bc\u2010Opioid Receptor, for Management of Moderate to Severe Acute Pain Following Abdominoplasty"],"prefix":"10.1111","volume":"19","author":[{"given":"Neil K.","family":"Singla","sequence":"first","affiliation":[{"name":"Lotus Clinical Research Pasadena California U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Skobieranda","sequence":"additional","affiliation":[{"name":"Trevena Inc. Chesterbrook Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Soergel","sequence":"additional","affiliation":[{"name":"Trevena Inc. Chesterbrook Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Salamea","sequence":"additional","affiliation":[{"name":"Trevena Inc. Chesterbrook Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Burt","sequence":"additional","affiliation":[{"name":"Trevena Inc. Chesterbrook Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Demitrack","sequence":"additional","affiliation":[{"name":"Trevena Inc. Chesterbrook Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-4396","authenticated-orcid":false,"given":"Eugene R.","family":"Viscusi","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.808"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/asj\/sju019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1090820X13510720"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181ef8fe5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000001400"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1516204"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2008\/11\/S105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1054\/jpai.2002.123652"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1223"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150214"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X104830"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.12286.1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238bba6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073940"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.248310"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35047086"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087254"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.201616"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.06.011"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2495"},{"key":"e_1_2_9_22_1","first-page":"185","article-title":"Structure\u2010based discovery of opioid analgesics with reduced side effects","volume":"537","author":"Manglik A","year":"2016","journal-title":"Nat Biotechnol"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000363"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S137952"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199909000-00022"},{"key":"e_1_2_9_26_1","unstructured":"Physician Desk Reference.Morphine Sulfate Drug Summary from Physician's Desk Reference Digital Format.https:\/\/www.pdr.net\/drug-summary\/Morphine-Sulfate-Oral-Solution-morphine-sulfate-1228.8394#6(accessed January 14 2019)"},{"key":"e_1_2_9_27_1","unstructured":"U.S. Food and Drug Administration.Guidance for Industry. Analgesic Indications: Developing Drug and Biological Products. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER);2014.https:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm384691.pdf(accessed January 14 2019)"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/NUR.0b013e3182503fd6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.08.010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.11.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S171013"},{"issue":"1","key":"e_1_2_9_33_1","first-page":"1","article-title":"Physician practice patterns and treatment challenges in acute postoperative pain management. PAINWeek abstract book 2017","volume":"129","author":"Gan TJ","year":"2017","journal-title":"Postgrad Med"},{"key":"e_1_2_9_34_1","first-page":"705","article-title":"Acute pain is associated with chronic opioid use after total knee arthroplasty","volume":"43","author":"Hsia H\u2010L","year":"2018","journal-title":"Reg Anesth Pain Med"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm4010829"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmn.2011.06.008"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1P438"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2017.11.098"}],"container-title":["Pain Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpapr.12801","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/papr.12801","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/papr.12801","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/papr.12801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T14:47:03Z","timestamp":1693406823000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/papr.12801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,24]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/papr.12801"],"URL":"https:\/\/doi.org\/10.1111\/papr.12801","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735908163.793581985","asserted-by":"object"}]},"ISSN":["1530-7085","1533-2500"],"issn-type":[{"value":"1530-7085","type":"print"},{"value":"1533-2500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,24]]},"assertion":[{"value":"2019-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}