{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:12:04Z","timestamp":1783649524778,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 is an oral vanin\u20101 and vanin\u20102 inhibitor, which demonstrated promising effects on epithelial cell protection and reduction of inflammatory mediators in preclinical studies, as well as an acceptable safety profile in a previous single\u2010rising\u2010dose trial. Here, we report the results of a double\u2010blind, randomized, placebo\u2010controlled, multiple rising dose study, which investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 in healthy male volunteers following oral administration of single and multiple rising doses over 18\u2009days in total. Thirty subjects were treated (18\u201350\u2009years of age; body mass index: 18.5\u201329.9\u2009kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ); each dose group included 10 subjects, of which eight were administered\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 (15, 30, or 60\u2009mg) and two were administered placebo after an overnight fast of \u2265\u200910\u2009h. With multiple rising doses,\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 appeared to effectively inhibit the conversion of pantetheine to pantothenic acid.\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 achieved rapid absorption after administration (median time from dosing to maximum measured concentration of the analyte in plasma: ~1\u2009h) and plasma concentrations generally increased in a dose\u2010proportional manner, with the majority excreted in urine within the first 24\u2009h after dosing. Most adverse events reported were of mild or moderate severity, e.g., headache, dizziness, and abdominal discomfort. However, this study was temporarily halted after ophthalmologic adverse events judged to be drug\u2010related by the investigator were reported in six subjects treated with\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043. The study was discontinued prematurely due to the sponsor's decision to terminate the development of\n                    <jats:styled-content style=\"fixed-case\">BI<\/jats:styled-content>\n                    1595043 in all indications.\n                  <\/jats:p>","DOI":"10.1111\/cts.70285","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T16:46:09Z","timestamp":1757954769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety, Pharmacokinetics, and Pharmacodynamics of\n                    <scp>BI<\/scp>\n                    1595043, a Selective Vanin Inhibitor, in Phase 1 Clinical Trials Involving Healthy Volunteers"],"prefix":"10.1111","volume":"18","author":[{"given":"Anjli","family":"Kukreja","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Keller","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Shatillo","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Ingelheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Bauer","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Sharma","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Wojciekowski","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Visvanathan","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Aslanyan","sequence":"additional","affiliation":[{"name":"Veloxis Pharmaceuticals, Inc.  Cary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061640"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e3182a32b03"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419557"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18050918"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.111849"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.11.099"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163891"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108448"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.02.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2011.611509"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01480.x"},{"key":"e_1_2_10_13_1","unstructured":"\u201cA Study in Healthy Men to Test How Different Doses of BI 1595043 Are Tolerated \u201d (2024) accessed October 2024 https:\/\/clinicaltrials.gov\/study\/NCT04439838."},{"key":"e_1_2_10_14_1","unstructured":"\u201cA Study in Healthy Men to Test How Different Doses of BI 1595043 Are Tolerated \u2013 Adverse Events \u201d (2024) accessed October 2024 https:\/\/clinicaltrials.gov\/study\/NCT04439838?tab=results\u2010adverse\u2010events."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijo.IJO_2020_22"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000316481"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.809495"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.06.014"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00373.2020"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:42:52Z","timestamp":1769683372000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/cts.70285"],"URL":"https:\/\/doi.org\/10.1111\/cts.70285","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70285"}}