{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T03:36:07Z","timestamp":1769312167484,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Intestinal failure\u2010associated liver disease occurs in 20% to 30% of patients with short bowel syndrome and intestinal failure (SBS\u2010IF). Apraglutide is a glucagon\u2010like peptide\u20102 (GLP\u20102) analog in clinical development for the treatment of patients with SBS\u2010IF. This study assessed the potential for changes in exposure of apraglutide in individuals with impaired hepatic function versus healthy volunteers. In this Phase 1, open\u2010label, nonrandomized, single\u2010dose trial, apraglutide 3.5\u00a0mg was administered to participants with moderate hepatic impairment (Child\u2010Pugh B) or normal hepatic function. Primary pharmacokinetic endpoints were area under the plasma concentration\u2013time curve (AUC) from time 0 to infinity (AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ) or AUC from time 0 to last quantifiable concentration (AUC\n                    <jats:sub>last<\/jats:sub>\n                    ) if AUC\n                    <jats:sub>inf<\/jats:sub>\n                    could not be reliably estimated, AUC\n                    <jats:sub>0\u2013168\u00a0h<\/jats:sub>\n                    , and maximum observed plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ). Secondary endpoints included safety and tolerability. Each group comprised eight participants. No increased apraglutide exposure was observed in individuals with moderate hepatic impairment. A lower C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    of apraglutide was observed in individuals with moderate hepatic impairment versus those with normal hepatic function (C\n                    <jats:sub>max<\/jats:sub>\n                    = 58.7\u00a0vs 71.3\u00a0ng\/mL; AUC\n                    <jats:sub>inf<\/jats:sub>\n                    = 4086\u00a0vs 5351 h ng\/mL, respectively). The respective geometric mean ratios were 0.835 and 0.936 for C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    , and the upper bounds of their 90% confidence intervals indicate that participants with moderate hepatic impairment were not overexposed to apraglutide versus those with normal hepatic function. Adverse events were mild or moderate in severity. The results of this trial suggest that apraglutide does not require dose alteration in patients with mild and moderate hepatic impairment.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70006","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:04:11Z","timestamp":1768622651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Safety of Single\u2010Dose Apraglutide in Individuals with Normal and Impaired Hepatic Function: A Phase 1, Open\u2010Label Trial"],"prefix":"10.1002","volume":"15","author":[{"given":"Gerard","family":"Greig","sequence":"first","affiliation":[{"name":"Ironwood Pharmaceuticals Inc.  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Hay","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc.  Boston MA USA"},{"name":"Certara  Radnor PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Valencia","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mena","family":"Boules","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Masior","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals Inc.  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2019.11.013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.30345.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.262238"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607114520994"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2014.08.017"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2372"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2012.08.007"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-132-7-200004040-00003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607113517717"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781405195805.ch15"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.1053"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15143169"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005957"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.31068"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1174308"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2389"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.9b00016"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01909"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2223"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.001582"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2423"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"key":"e_1_2_11_24_1","article-title":"Efficacy and safety of apraglutide once\u2010weekly in patients with short bowel syndrome and intestinal failure (SBS\u2010IF): the STARS study, a global phase 3, randomized, placebo\u2010controlled, double\u2010blind trial","author":"Joly F","journal-title":"Oral presentation at DDW 2024"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2024.10.011"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2362"},{"key":"e_1_2_11_27_1","doi-asserted-by":"crossref","unstructured":"GreigG YoussefNN LiC BolognaniF.The effect of apraglutide on gastric emptying in healthy individuals: a phase 1 randomized placebo\u2010controlled double\u2010blind single\u2010center trial. Poster presented at DDW2024; Poster Su1949.","DOI":"10.1016\/S0016-5085(24)02508-3"},{"key":"e_1_2_11_28_1","volume-title":"US prescribing information","author":"Gattex (teduglutide)","year":"2024"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-838X(11)60221-9"},{"key":"e_1_2_11_30_1","volume-title":"NCT05018286: open\u2010label extension trial to evaluate the long\u2010term safety of apraglutide in short bowel syndrome (STARS Extend)","author":"ClinicalTrials.gov"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70006","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:23:25Z","timestamp":1769264605000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cpdd.70006"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70006","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70006"}}