{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:54:10Z","timestamp":1777949650763,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Spleen tyrosine kinase (SYK) has broad biological functions in inflammation and immunity. The orally administered SYK inhibitor BI\u2009894416 was investigated in a single\u2010rising\u2010dose Phase I study in healthy volunteers and in a combined single\u2010 and multiple\u2010rising\u2010dose Phase Ib study in patients with mild asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The single\u2010blinded, partially randomised, placebo\u2010controlled Phase I study evaluated single doses of BI\u2009894416 (3\u201370\u2009mg) in healthy volunteers. The single\u2010blinded, randomised, placebo\u2010controlled Phase Ib study in patients with mild asthma evaluated three single doses (75\u2013170\u2009mg) and four multiple doses (10\u201360\u2009mg) of BI\u2009894416 over an interval of 9\u2009days. The primary objective of both studies was safety and tolerability, assessing the proportion of participants with drug\u2010related adverse events (AEs). Secondary endpoints related to pharmacokinetics and efficacy (Phase Ib study only).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>All except one randomised participant completed treatment (56 healthy volunteers and 68 mild asthmatics [29 received a single dose and 39 received multiple doses]). The most frequent drug\u2010related AEs were headache, diarrhoea and nausea (all of mild\/moderate intensity). No serious AEs occurred. BI\u2009894416 was rapidly absorbed with median time\u2010to\u2010peak concentration 0.5\u20131.0\u2009h; exposure increased in a dose\u2010dependent manner. Basophils and nasal epithelial cells showed dose\u2010dependent modulation of activation\u2010 and disease\u2010associated genes and pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>BI\u2009894416 was safe and well tolerated in healthy volunteers and mild asthmatics. Results from target engagement biomarkers demonstrated treatment\u2010 and dose\u2010dependent cellular modulation, potentially leading to decreased airway inflammation and airway obstruction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70329","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T06:26:10Z","timestamp":1770445570000},"page":"2660-2674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, tolerability, pharmacokinetics and pharmacodynamics of the spleen tyrosine kinase inhibitor BI\u2009894416 in healthy volunteers and patients with asthma"],"prefix":"10.1111","volume":"183","author":[{"given":"Saskia","family":"Carstensen\u2010Aur\u00e8che","sequence":"first","affiliation":[{"name":"Fraunhofer Institute of Toxicology and Experimental Medicine ITEM Clinical Airway Research  Hannover Germany"},{"name":"German Center for Lung Research (DZL\u2010BREATH)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Litzenburger","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy","family":"De Sousa","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharmaceutical Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Sailer","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewald","family":"Benediktus","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Delic","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Clinical Development &amp; Operations Boehringer Ingelheim Pharma GmbH &amp; Co. 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