{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:13:27Z","timestamp":1763748807330},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asciminib, a first\u2010in\u2010class allosteric BCR::ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP)\u00a0is used in the treatment of chronic myeloid leukemia. We describe a randomized, single\u2010dose, open\u2010label, four\u2010period crossover study in healthy adult participants (N\u00a0=\u00a024) which evaluated the relative bioavailability of a single 40\u2010mg dose of asciminib in pediatric formulation (1\u2010mg mini\u2010tablets) compared with the reference adult tablet under fasted conditions. Additionally, the effect of food on the bioavailability of the mini\u2010tablet formulation was evaluated. Under fasted conditions, asciminib exposure was similar for both formulations (geometric mean [G<jats:sub>mean<\/jats:sub>] area under the concentration\u2013time curve from time 0 to infinity [AUC<jats:sub>inf<\/jats:sub>] 5970 and 5700\u00a0ng \u00d7h\/mL, respectively). Food decreased the AUC<jats:sub>inf<\/jats:sub> and maximum plasma concentration (C<jats:sub>max<\/jats:sub>) of the asciminib mini\u2010tablets; this effect was more pronounced with a high\u2010fat meal (G<jats:sub>mean<\/jats:sub> ratios [90% confidence interval]: fasted\/low\u2010fat meal, 0.42 [0.38\u2013047], 0.32 [0.28\u20130.37], respectively; fasted\/high\u2010fat meal, 0.30 [0.27\u20130.34], 0.22 [0.19\u20130.25], respectively). The mini\u2010tablets were assessed to be easy to ingest with good palatability. Asciminib doses for a pivotal pediatric clinical trial will be defined using physiologically based pharmacokinetic modeling, which will consider the age and the higher food effect observed with the mini\u2010tablets.<\/jats:p>","DOI":"10.1002\/cpdd.1213","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T16:47:35Z","timestamp":1673282855000},"page":"484-492","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Relative Bioavailability and Food Effect of Asciminib Pediatric Mini\u2010tablet Formulation Compared to the Reference Tablet Formulation in Healthy Adult Participants"],"prefix":"10.1002","volume":"12","author":[{"given":"Matthias","family":"Hoch","sequence":"first","affiliation":[{"name":"Novartis Institutes for Biomedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidiya","family":"Bebrevska","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namrata","family":"Singh","sequence":"additional","affiliation":[{"name":"Novartis Healthcare Pvt Ltd  Rangareddy Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Hourcade\u2010Potelleret","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-015-2314-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27827"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01040"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21702"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2020.106458"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902328"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2019.1594449"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1926"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13252"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1019"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009984"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-151198"},{"key":"e_1_2_9_15_1","unstructured":"U.S. Food and Drug Administration. FDA Center for Drug Evaluation and Research Guidance for Industry.Assessing the effects of food on drugs in INDs and NDAs \u2013 Clinical Pharmacology Considerations;2019.https:\/\/www.fda.gov\/media\/121313\/download. Accessed July 12 2022."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.602"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1213","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T02:30:58Z","timestamp":1692585058000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/cpdd.1213"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1213","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]},"assertion":[{"value":"2022-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}