Safety, tolerability, pharmacokinetics and pharmacodynamics of the spleen tyrosine kinase inhibitor BI 894416 in healthy volunteers and patients with asthma
Carstensen-Aurèche S, Litzenburger T, De Sousa D, Sailer R, Benediktus E, Delic D, Müller F, Müller M, Hohlfeld JM (2026)
Publication Type: Journal article
Publication year: 2026
Journal
DOI: 10.1111/bph.70329
Abstract
Background and Purpose: Spleen tyrosine kinase (SYK) has broad biological functions in inflammation and immunity. The orally administered SYK inhibitor BI 894416 was investigated in a single-rising-dose Phase I study in healthy volunteers and in a combined single- and multiple-rising-dose Phase Ib study in patients with mild asthma. Experimental Approach: The single-blinded, partially randomised, placebo-controlled Phase I study evaluated single doses of BI 894416 (3–70 mg) in healthy volunteers. The single-blinded, randomised, placebo-controlled Phase Ib study in patients with mild asthma evaluated three single doses (75–170 mg) and four multiple doses (10–60 mg) of BI 894416 over an interval of 9 days. The primary objective of both studies was safety and tolerability, assessing the proportion of participants with drug-related adverse events (AEs). Secondary endpoints related to pharmacokinetics and efficacy (Phase Ib study only). Key Results: 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-related AEs were headache, diarrhoea and nausea (all of mild/moderate intensity). No serious AEs occurred. BI 894416 was rapidly absorbed with median time-to-peak concentration 0.5–1.0 h; exposure increased in a dose-dependent manner. Basophils and nasal epithelial cells showed dose-dependent modulation of activation- and disease-associated genes and pathways. Conclusion and Implications: BI 894416 was safe and well tolerated in healthy volunteers and mild asthmatics. Results from target engagement biomarkers demonstrated treatment- and dose-dependent cellular modulation, potentially leading to decreased airway inflammation and airway obstruction.
Involved external institutions
Boehringer Ingelheim Pharma GmbH & Co. KG
Germany (DE)
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) / Fraunhofer Institute for Toxicology and Experimental Medicine
Germany (DE)
Germany (DE)
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) / Fraunhofer Institute for Toxicology and Experimental Medicine
Germany (DE)
How to cite
APA:
Carstensen-Aurèche, S., Litzenburger, T., De Sousa, D., Sailer, R., Benediktus, E., Delic, D.,... Hohlfeld, J.M. (2026). Safety, tolerability, pharmacokinetics and pharmacodynamics of the spleen tyrosine kinase inhibitor BI 894416 in healthy volunteers and patients with asthma. British Journal of Pharmacology. https://doi.org/10.1111/bph.70329
MLA:
Carstensen-Aurèche, Saskia, et al. "Safety, tolerability, pharmacokinetics and pharmacodynamics of the spleen tyrosine kinase inhibitor BI 894416 in healthy volunteers and patients with asthma." British Journal of Pharmacology (2026).
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