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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EEluxadoline, a \u00b5-opioid receptor agonist and d-opioid receptor antagonist, exhibits rapid onset of action along with sustained efficacy over the 6-month treatment period as studied in the phase 3, double-blind, placebo-controlled IBS3001 and IBS3002 trials in patients with diarrhea-predominant irritable bowel syndrome.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eeluxadoline\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eirritable bowel syndrome with diarrhea\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIBD3001\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIBS3002\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003E\u00b5-opioid receptor agonist\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ed-opioid receptor antagonist\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eirritable bowel syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egastroenterology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EIrritable bowel syndrome with diarrhea (IBS-D), a common gastrointestinal (GI) disorder, is characterized by bloating, urgency, recurring abdominal pain, and loose, frequent stools in the absence of structural or biochemical abnormalities. Endogenous \u00b5- and d-opioid receptors are critical for the normal function and sensation of the GI tract. A novel mixed \u00b5-opioid receptor agonist and d-opioid receptor antagonist, eluxadoline, acts locally in the GI tract with low systemic absorption and oral bioavailability [Fujita W et al. \u003Cem\u003EBiochem Pharmacol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EWilliam D. Chey, MD, University of Michigan Health System, Ann Arbor, Michigan, USA, discussed the results of IBS3001 [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01553591\u0026amp;atom=%2Fspmdc%2F15%2F14%2F12.2.atom\u0022\u003ENCT01553591\u003C\/a\u003E] and IBS3002 [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01553747\u0026amp;atom=%2Fspmdc%2F15%2F14%2F12.2.atom\u0022\u003ENCT01553747\u003C\/a\u003E], 2 randomized, double-blind, placebo-controlled, phase 3 trials that evaluated the sustained efficacy of twice-daily treatment with eluxadoline in adults with IBS-D.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EBoth studies randomly assigned adults 1:1:1 to placebo twice daily, eluxadoline 75 mg BID, or eluxadoline 100 mg BID. Both studies were 26 weeks, and efficacy was assessed at week 12 for the FDA and at week 26 for the European Medicines Agency. IBS3002, conducted in the United States, United Kingdom, Canada, and Puerto Rico, concluded at 26 weeks. For IBS3001, conducted in the United States, United Kingdom, and Canada, treatment was extended for an additional 26 weeks to assess the safety of long-term use.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EInclusion criteria comprised IBS-D (Rome III criteria), average worst abdominal pain (WAP) score \u0026gt;\u20053 (scale 0 to 10), average stool consistency Bristol Stool Scale (BSS) score \u2265\u20055.5 (scale 1 to 7), at least 5 days with a BSS score \u2265\u20055.5 during the 4-week screening period, and IBS-D global symptom score \u2265\u20052.0 (scale 0 to 4). Patients with inflammatory bowel or celiac disease, prior pancreatitis, sphincter of Oddi dysfunction, and other GI conditions or elevated lipase, alanine, or aspartate aminotransferases were excluded.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe composite efficacy end point was response, evaluated at weeks 1 through 12 (FDA primary end point) and weeks 1 through 26 (European Medicines Agency primary end point). Responders were defined as having an improvement in daily pain (WAP scores improved by \u2265\u200530% in the past 24 hours compared with average baseline pain) and daily stool consistency (BSS score \u0026lt;\u20055) on at least 50% of days.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EBaseline characteristics of enrolled patients in IBS3001 (n\u2005=\u20051282) and IBS3002 (n\u2005=\u20051146) were comparable. Mean BSS and WAP were both \u0026gt;\u20056, indicating a severely affected population. Efficacy results are shown in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/14\/12.2\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Primary Composite Efficacy End PointNS, not significant.Reproduced with permission from WD Chey, MD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2052287187\u0022 data-figure-caption=\u0022Primary Composite Efficacy End PointNS, not significant.Reproduced with permission from WD Chey, MD.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/14\/12.2\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/14\/12.2\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/14\/12.2\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16781\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EPrimary Composite Efficacy End Point\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ENS, not significant.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EReproduced with permission from WD Chey, MD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EEfficacy of eluxadoline was seen within week 1, with maximum benefit achieved in weeks 4 to 6 and sustained over the 6-month efficacy evaluation period. Efficacy was seen in both men and women. Significantly more patients taking either eluxadoline dose reported \u2265\u200575% urgency-free days (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001) and decrease in bowel movement frequency (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.001) than those taking placebo.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EAdverse events were reported slightly more often by those in the eluxadoline groups; GI-related events were the most common.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003ESphincter of Oddi spasm events occurred in 10 patients taking eluxadoline who had prior cholecystectomy; symptoms were reversible with withdrawal of drug. Pancreatitis occurred in 4 patients in the eluxadoline groups. No deaths or surgery resulted from these events.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003ETo conclude, eluxadoline offers an effective new therapeutic option for patients with IBS-D; however, a risk of mild pancreatitis was seen.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/14\/12.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzlhap\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlhap\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}