{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:51:58Z","timestamp":1788558718050,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Linaclotide, a guanylate cyclase\u2010C agonist, was recently approved in the United States for the treatment of children 6\u201317 years of age with functional constipation (FC). This study evaluated the dose\u2010response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2\u20135 years of age with FC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 2, randomized, double\u2010blind, placebo\u2010controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72\u2009\u03bcg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72\u2009\u03bcg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs\/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72\u2009\u03bcg group versus placebo. A dose\u2010response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment\u2010emergent AEs, one of which was treatment\u2010related (mild diarrhea). All AEs were mild or moderate and none were severe.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72\u2009\u03bcg versus placebo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpn3.12306","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T09:31:06Z","timestamp":1720085466000},"page":"510-518","source":"Crossref","is-referenced-by-count":8,"title":["Safety and efficacy of linaclotide in children aged 2\u20135 years with functional constipation: Phase 2, randomized study"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8982-0336","authenticated-orcid":false,"given":"Carlo","family":"Di Lorenzo","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition Nationwide Children's Hospital Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Robert","sequence":"additional","affiliation":[{"name":"HealthStar Research Hot Springs Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Rodriguez\u2010Araujo","sequence":"additional","affiliation":[{"name":"AbbVie Inc. Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Clinical Development Ironwood Pharmaceuticals Inc. Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangang","family":"Xie","sequence":"additional","affiliation":[{"name":"AbbVie Inc. Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Nurko","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Saps","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology University of Miami Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10215087"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-69560-8_45"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.02.029"},{"key":"e_1_2_9_6_1","article-title":"Paediatrics: how to manage functional constipation","volume":"10","author":"Leung AK","year":"2021","journal-title":"Drugs Context"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.12.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3122\/jabfm.16.3.213"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04273.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181e67058"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000266"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-1009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00888-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.04.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000003280"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.09.005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03320.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03884.x"},{"key":"e_1_2_9_20_1","unstructured":"U.S. Food and Drug Administration. Linzess\u00ae (linaclotide). Highlights of prescribing information. 2023. 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