{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:58:52Z","timestamp":1780905532401,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"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":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tenapanor, a first\u2010in\u2010class, minimally systemic inhibitor of intestinal sodium\/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS\u2010C) in adults based on two randomized, placebo\u2010controlled, phase III studies (T3MPO\u20101 [NCT02621892], T3MPO\u20102 [NCT02686138]). The open\u2010label T3MPO\u20103 extension study (NCT02727751) enrolled patients who completed these studies to investigate long\u2010term safety and tolerability of tenapanor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who completed T3MPO\u20101 (16\u2009weeks) or T3MPO\u20102 (26\u2009weeks) were eligible for enrollment in T3MPO\u20103. Patients in T3MPO\u20103 received open\u2010label tenapanor 50\u2009mg twice a day for up to an additional 39 (T3MPO\u20101) or 26 (T3MPO\u20102) weeks. Treatment\u2010emergent adverse events (TEAEs) were evaluated in the entire T3MPO\u20103 safety population and in patients who received a total of \u226552\u2009weeks of tenapanor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>A total of 312 patients were enrolled in T3MPO\u20103; 90 received \u226552\u2009weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received \u226552\u2009weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received \u226552\u2009weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO\u20103 study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tenapanor was tolerable over \u226552\u2009weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS\u2010C.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14658","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:10:05Z","timestamp":1693912205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Long\u2010term safety of tenapanor in patients with irritable bowel syndrome with constipation in the <scp>T3MPO<\/scp>\u20103 study"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4479-1188","authenticated-orcid":false,"given":"Anthony J.","family":"Lembo","sequence":"first","affiliation":[{"name":"Digestive Disease Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Friedenberg","sequence":"additional","affiliation":[{"name":"Great Lakes Gastroenterology  Mentor Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.","family":"Fogel","sequence":"additional","affiliation":[{"name":"Digestive Health Center of Michigan  Chesterfield Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Edelstein","sequence":"additional","affiliation":[{"name":"Ardelyx, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Ardelyx, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Ardelyx, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Ardelyx, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Chey","sequence":"additional","affiliation":[{"name":"Michigan Medicine  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,5]]},"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\/s41395-018-0084-x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(20)30217-X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.12.021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01456.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0733-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.08.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2011.623157"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2014.08.839"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13696998.2020.1799816"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001036"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.04.016"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.10.036"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2018.10.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007790"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01215-9"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam6474"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(18)31424-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000516"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001056"},{"key":"e_1_2_10_23_1","unstructured":"U.S. Dept of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).Guidance for industry: irritable bowel syndrome \u2014 Clinical evaluation of drugs for treatment.2012. 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Accessed November 2 2022.https:\/\/www.fda.gov\/media\/78622\/download"}],"updated-by":[{"DOI":"10.1111\/nmo.70346","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000}}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.14658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:17:58Z","timestamp":1699269478000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.14658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,5]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/nmo.14658"],"URL":"https:\/\/doi.org\/10.1111\/nmo.14658","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,5]]},"assertion":[{"value":"2022-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14658"}}