{"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":1769312167534,"version":"3.49.0"},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"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                    This randomized, open\u2010label, 2\u2010period crossover study evaluated food effects on SPH3348 pharmacokinetics (PK) and safety in 16 healthy participants receiving a single 480\u2010mg dose under fasting and high\u2010fat fed conditions. PK profiling involved serial blood sampling at 15 predefined time points per period, while safety assessments included continuous monitoring of adverse events throughout the study. PK analysis revealed pronounced food\u2010dependent alterations. Under fed conditions, the median time to peak concentration was delayed by 1\u00a0hour compared to fasting (4.00 vs. 3.00\u00a0hours), reflecting a slowdown in absorption rate (median time to peak concentration delay was statistically significant [\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.05 by Wilcoxon signed\u2010rank test]). PK analysis demonstrated marked food\u2010induced increases in systemic exposure. The fed\u2010to\u2010fasted geometric mean ratios and 90% confidence intervals were 1.9023 (1.5975\u20102.2653) for maximum concentration and 2.3667 (2.1140\u20102.6490) for AUC from time zero extrapolated to infinity, both exceeding the 1.25 threshold for bioequivalence. These exposure increases (greater than 2\u2010fold) confirm that meal\u2010induced enhancement of absorption is clinically significant. Safety profiles remained comparable between dosing conditions, with adverse event incidence rates of 13.3% (fasting) versus 18.8% (fed) and predominantly mild severity, primarily involving transient gastrointestinal events. These findings indicate that while food intake significantly increases SPH3348 bioavailability and slightly delays absorption kinetics, both fasting and fed administrations are well tolerated following single\u2010dose exposure. The observed PK modifications highlight the necessity of standardizing dietary conditions in clinical use to ensure consistent drug exposure. The systematic characterization of these food effects provides critical evidence for optimizing dosing regimens and informing subsequent\u2010phase clinical development, particularly regarding administration guidelines to manage variability between patients.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1590","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T19:03:18Z","timestamp":1755889398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Food on the Pharmacokinetics and Safety of a Novel c\u2010Met Inhibitor SPH3348: A Single\u2010Center, Randomized, Open\u2010Label, Single\u2010Dose, 2\u2010Period, 2\u2010Sequence Crossover Study"],"prefix":"10.1002","volume":"15","author":[{"given":"Zhuo","family":"Chen","sequence":"first","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Yu","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyin","family":"Feng","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingli","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"},{"name":"Department of Pharmacy\/Evidence\u2010Based Pharmacy Center West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai","family":"Qian","sequence":"additional","affiliation":[{"name":"Shanghai Pharmaceuticals Holding Co., Ltd.  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weikao","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Pharmaceuticals Holding Co., Ltd.  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linrui","family":"Cai","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Du","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfeng","family":"Du","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Zou","sequence":"additional","affiliation":[{"name":"National Drug Clinical Trial Institution of West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834011422556"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines3010071"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00441-8"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004407"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.08.015"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02363"},{"key":"e_1_2_11_8_1","unstructured":"Assessing the Effects of Food on Drugs in INDs and NDAs \u2013 Clinical Pharmacology Considerations Available from:https:\/\/www.fda.gov\/media\/121313\/download"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.03.002"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1590","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1590","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1590","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:23:20Z","timestamp":1769264600000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cpdd.1590"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1590","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]},"assertion":[{"value":"2025-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1590"}}