{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:24:47Z","timestamp":1783761887540,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005565","name":"Janssen Biotech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005565","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prucalopride is a selective, high\u2010affinity serotonin type 4 receptor agonist approved for the treatment of chronic idiopathic constipation (CIC) in adults. We investigated the impact of prucalopride cessation and re\u2010treatment on efficacy and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were from two randomized controlled trials in adults with CIC. In a dose\u2010finding trial, complete spontaneous bowel movements (CSBMs) and treatment\u2010emergent adverse events (TEAEs) were assessed during a 4\u2010week run\u2010out period after a 4\u2010week treatment period (TP; prucalopride 0.5\u20134\u2009mg once daily or placebo). In a re\u2010treatment trial, CSBMs and TEAEs were assessed during two 4\u2010week TPs (prucalopride 4\u2009mg once daily or placebo) separated by a 2\u2010 or 4\u2010week washout period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In the dose\u2010finding trial (<jats:italic>N<\/jats:italic>\u00a0=\u00a0234; 43\u201348 patients\/group), mean CSBMs\/week and the proportion of responders (\u22653 CSBMs\/week) were higher with prucalopride than placebo during the TP, but similar in all groups 1\u20134\u2009weeks after treatment cessation. TEAEs were less frequent following treatment cessation. In the re\u2010treatment trial (efficacy analyses: prucalopride, <jats:italic>n<\/jats:italic>\u00a0=\u00a0189; placebo, <jats:italic>n<\/jats:italic>\u00a0=\u00a0205), the proportion of responders was similar in both TPs and significantly higher (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001) with prucalopride (TP1, 38.6%; TP2, 36.0%) than placebo (TP1, 10.7%; TP2, 11.2%). Most patients who responded to prucalopride in TP1 responded again in TP2 (71.2%). TEAEs were less frequent in TP2 than TP1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Prucalopride cessation resulted in a loss of clinical effect to baseline levels within 7\u2009days. Similar efficacy and safety were observed between TP1 and TP2 after prucalopride was re\u2010initiated following a washout period.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14563","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T15:30:20Z","timestamp":1680535820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of treatment cessation and re\u2010treatment in randomized controlled trials of prucalopride in patients with chronic idiopathic constipation"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-0994","authenticated-orcid":false,"given":"Jimmy","family":"Hinson","sequence":"first","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc.  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-4122","authenticated-orcid":false,"given":"Heinrich","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals International AG  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-2009","authenticated-orcid":false,"given":"Brian","family":"Terreri","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc.  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5962-9271","authenticated-orcid":false,"given":"Mena","family":"Boules","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc.  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.031"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.164"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709002985"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04273.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-011-1639-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0633-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S239205"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05843.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000614"},{"issue":"4","key":"e_1_2_10_11_1","first-page":"S55","article-title":"Update on the management of chronic idiopathic constipation","volume":"25","author":"Lacy BE","year":"2019","journal-title":"Am J Manag Care"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162404"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2019.1620104"},{"key":"e_1_2_10_14_1","unstructured":"Shire.MOTEGRITY (prucalopride) Prescribing Information.2020. Accessed November 24 2022.https:\/\/www.shirecontent.com\/PI\/PDFs\/MOTEGRITY_USA_ENG.pdf"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12832"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4147-9"},{"key":"e_1_2_10_17_1","unstructured":"European Medicines Agency.Resolor (prucalopride) Summary of product characteristics.2020. Accessed November 24 2022.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/resolor\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.06.010"},{"key":"e_1_2_10_19_1","unstructured":"ClinicalTrials.gov.Trial to evaluate the efficacy and safety of R093877 in patients with chronic idiopathic constipation.2008. 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