{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:22:10Z","timestamp":1786926130007,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study evaluated the effects of eluxadoline, a mixed \u03bc\u2010opioid receptor (OR) and \u03ba\u2010OR agonist and \u03b4\u2010OR antagonist, on cardiac repolarization. This evaluator\u2010blinded, placebo\u2010 and positive\u2010controlled, 4\u2010period crossover study randomized healthy men and women to single oral doses of eluxadoline (therapeutic dose 100\u00a0mg or supratherapeutic dose 1000\u00a0mg), moxifloxacin 400\u00a0mg, or placebo. QT data were corrected using individual custom correction (QTcI). The primary endpoint was the change from baseline in QTcI intervals (\u0394QTcI) between eluxadoline and placebo (\u0394\u0394QTcI). An upper bound of the 95% confidence interval around \u0394\u0394QTcI of 10\u00a0milliseconds was considered clinically significant. Concentration\u2013QTc data were analyzed using a repeated\u2010measures, mixed\u2010effects linear model. Sixty\u2010four volunteers were treated, and 58\u00a0completed the study. Assay sensitivity was demonstrated with moxifloxacin (noted by \u0394\u0394QTcI of 11.94\u00a0milliseconds). The maximum \u0394\u0394QTcI for eluxadoline 1000\u00a0mg was 4.10\u00a0milliseconds 1 hour postdose (1\u2010sided 95% upper\u00a0confidence bound, 5.81\u00a0milliseconds), and for eluxadoline 100\u00a0mg was\u00a01.20\u00a0milliseconds at 0.5 hours postdose (1\u2010sided 95% upper confidence bound, 2.91 milliseconds). Primary \u0394\u0394QTcI results were confirmed using Fridericia's formula for QTc. Categorical, morphological, and concentration\u2013QTc analyses were consistent with the primary and secondary findings. There were no significant gender effects on \u0394\u0394QTcI values. The most common adverse events were contact dermatitis and nausea (12.5% each) and dizziness (10.9%); adverse events were more frequent in the eluxadoline 1000\u00a0mg group. In conclusion, eluxadoline, at therapeutic or supratherapeutic doses, did not significantly prolong QT intervals, and was safe and generally well tolerated in this study population.<\/jats:p>","DOI":"10.1002\/cpdd.453","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T14:37:05Z","timestamp":1523889425000},"page":"727-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of Eluxadoline Effect on Cardiac Repolarization"],"prefix":"10.1002","volume":"7","author":[{"given":"Laura","family":"Bonifacio","sequence":"first","affiliation":[{"name":"Lodestar Pharma Consulting, LLC  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Hunt","sequence":"additional","affiliation":[{"name":"PPD  Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"McIntyre","sequence":"additional","affiliation":[{"name":"IntelliDev Consulting, LLC  Lansdale PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard S.","family":"Dove","sequence":"additional","affiliation":[{"name":"Consultant to Allergan plc  Madison NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Covington","sequence":"additional","affiliation":[{"name":"Former employee of Furiex Pharmaceuticals, Inc. an affiliate of Allergan plc  Madison NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.032"},{"key":"e_1_2_7_3_1","first-page":"71","article-title":"The epidemiology of irritable bowel syndrome","volume":"6","author":"Canavan C","year":"2014","journal-title":"Clin Epidemiol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.029"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e318247157c"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02068.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.05.042"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajgsup.2014.5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2004.00513.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1712"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.28.2.156"},{"issue":"1","key":"e_1_2_7_12_1","first-page":"1","article-title":"Loperamide\u2010induced constipation in healthy subjects\u2014an experimental model to evaluate the anti\u2010constipation effect of methylnaltrexone","volume":"72","author":"Nassif A","year":"2011","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.236547"},{"issue":"1","key":"e_1_2_7_14_1","first-page":"1","article-title":"Eluxadoline single\u2010 and repeat\u2010dose pharmacokinetics in healthy volunteers","volume":"4","author":"Davenport JM","year":"2015","journal-title":"Clin Pharmacol Drug Dev"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.442"},{"issue":"7","key":"e_1_2_7_16_1","first-page":"438","article-title":"Eluxadoline (Viberzi): a mu\u2010opioid receptor agonist for the treatment of irritable bowel syndrome with diarrhea","volume":"42","author":"Maltz F","year":"2017","journal-title":"P T"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.964"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.04.006"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.542"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505180"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0756-7"},{"key":"e_1_2_7_22_1","unstructured":"US Food and Drug Administration.Guidance for industry\u2014E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs.2005.https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/ucm073153.pdf. 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