{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:42:58Z","timestamp":1747183378836,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>MD\u20107246, a delayed\u2010release formulation of linaclotide, is designed to target the ileocaecal junction and caecum with the aim of relieving abdominal pain independently of bowel function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the efficacy, safety and dose\u2013response of MD\u20107246 in patients with irritable bowel syndrome with diarrhoea (IBS\u2010D).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomised, double\u2010blind, phase 2 clinical trial enrolled adult patients with IBS\u2010D (Rome IV criteria). Patients were randomised to placebo or once\u2010daily oral MD\u20107246 300, 600 or 1200\u2009\u03bcg for 12\u2009weeks. Abdominal and bowel symptoms were assessed daily. Key efficacy endpoints were change from baseline in abdominal pain and responder rates for a 30% reduction in abdominal pain in 6\/12\u2009weeks. Additional abdominal pain responder and exploratory bowel function endpoints were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 388 randomised patients, there was no significant difference in mean change from baseline in abdominal pain between the MD\u20107246 300\u2009\u03bcg, 600\u2009\u03bcg and 1200\u2009\u03bcg groups and placebo (\u22121.93, \u22121.58, \u22121.95 and\u2009\u2212\u20092.01, respectively; <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05 for each group vs placebo). The abdominal pain responder rates in the MD\u20107246 groups were similar to or lower than those in the placebo group. All doses of MD\u20107246 had a minimal effect on bowel function and were generally well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MD\u20107246 at the doses studied did not improve abdominal pain relative to placebo in an IBS\u2010D patient population. Similarly, most additional efficacy endpoints showed no improvement with MD\u20107246 relative to placebo.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17274","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T05:19:06Z","timestamp":1667452746000},"page":"192-204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Randomised clinical trial: effects of <scp>MD<\/scp>\u20107246 on irritable bowel syndrome with diarrhoea"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4479-1188","authenticated-orcid":false,"given":"Anthony","family":"Lembo","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Braden","family":"Kuo","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramesh","family":"Boinpally","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  Madison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Li","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc.  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhuja","family":"Mallick","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  Madison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wieslaw","family":"Bochenek","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  Madison New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilmin","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc.  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1038\/s41395-018-0084-x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1016\/S0140-6736(20)31548-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1053\/j.gastro.2016.02.031"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1053\/j.gastro.2020.04.014"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1016\/S2468-1253(20)30217-X"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1186\/s12955-017-0611-2"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1016\/j.cgh.2019.08.016"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1053\/j.gastro.2022.04.017"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.14309\/ajg.0000000000000967"},{"unstructured":"U.S. Food and Drug Administration.Linzess\u00ae (linaclotide). Highlights of prescribing information.2021. 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