{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:13:55Z","timestamp":1793690035718,"version":"4.5.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Linaclotide, a guanylate cyclase\u2010C agonist, was recently approved in the United States for the treatment of children 6\u201317 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7\u201317 years old with irritable bowel syndrome with constipation (IBS\u2010C).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this 4\u2010week, randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group, Phase 2 study, children with IBS\u2010C were randomized to once\u2010daily placebo or linaclotide (Dose A: 18 or 36\u2009\u00b5g, B: 36 or 72\u2009\u00b5g, and C: 72\u2009\u00b5g or 145\u2009\u00b5g, or 290\u2009\u00b5g); those aged 7\u201311 years in a 1:1:1:1 allocation based on weight (18 to &lt;35\u2009kg:18\u2009\u00b5g, 36\u2009\u00b5g, or 72\u2009\u00b5g; or \u226535\u2009kg: 36\u2009\u00b5g, 72\u2009\u00b5g, or 145\u2009\u00b5g), and those aged 12\u201317 years in a 1:1:1:1:1 allocation (the higher option of Doses A\u2013C or 290\u2009\u00b5g). The primary efficacy endpoint was a change from baseline in 4\u2010week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Efficacy, safety, and tolerability were assessed in 101 patients. In the intent\u2010to\u2010treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290\u2009\u00b5g: 3.26) compared with placebo. The most reported treatment\u2010emergent adverse events were diarrhea and pain, with most cases being mild and none being severe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jpn3.12103","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T02:04:33Z","timestamp":1703815473000},"page":"539-547","source":"Crossref","is-referenced-by-count":10,"title":["Safety and efficacy of linaclotide in children aged 7\u201317 years with irritable bowel syndrome with constipation"],"prefix":"10.1002","volume":"78","author":[{"given":"Carlo","family":"Di Lorenzo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology &amp; Nutrition Nationwide Children's Hospital Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Nurko","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Hyams","sequence":"additional","affiliation":[{"name":"Connecticut Children's Medical Center Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Rodriguez\u2010Araujo","sequence":"additional","affiliation":[{"name":"AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc. Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Saps","sequence":"additional","affiliation":[{"name":"University of Miami Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Simon","sequence":"additional","affiliation":[{"name":"University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i20.6013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(96)70246-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm.2013.19.1.90"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004703-200612000-00001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01722.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181e67058"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i21.2211"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/pch\/pxy121"},{"key":"e_1_2_10_11_1","unstructured":"US Food and Drug Administration. Linzess\u00ae (linaclotide). Highlights of prescribing information. Published online2023. Accessed June 14 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/\/202811s021lbl.pdf"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000003296"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.04.040"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.03.002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709011203"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.08.041"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0084-x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1527303"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.12.036"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-021-00444-4"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2021.5750"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00797"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.254"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.255"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31824cf08a"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050577"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm16214"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-021-04013-2"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2022.21893"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-018-0769-z"}],"container-title":["Journal of Pediatric Gastroenterology and Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpn3.12103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T03:29:58Z","timestamp":1726716598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jpn3.12103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,28]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/jpn3.12103"],"URL":"https:\/\/doi.org\/10.1002\/jpn3.12103","archive":["Portico"],"relation":{},"ISSN":["0277-2116","1536-4801"],"issn-type":[{"value":"0277-2116","type":"print"},{"value":"1536-4801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,28]]}}}