Safety, Pharmacokinetics, and Pharmacodynamics of BI 1595043, a Selective Vanin Inhibitor, in Phase 1 Clinical Trials Involving Healthy Volunteers

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ABSTRACT BI 1595043 is an oral vanin‐1 and vanin‐2 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‐rising‐dose trial. Here, we report the results of a double‐blind, randomized, placebo‐controlled, multiple rising dose study, which investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1595043 in healthy male volunteers following oral administration of single and multiple rising doses over 18 days in total. Thirty subjects were treated (18–50 years of age; body mass index: 18.5–29.9 kg/m 2 ); each dose group included 10 subjects, of which eight were administered BI 1595043 (15, 30, or 60 mg) and two were administered placebo after an overnight fast of ≥ 10 h. With multiple rising doses, BI 1595043 appeared to effectively inhibit the conversion of pantetheine to pantothenic acid. BI 1595043 achieved rapid absorption after administration (median time from dosing to maximum measured concentration of the analyte in plasma: ~1 h) and plasma concentrations generally increased in a dose‐proportional manner, with the majority excreted in urine within the first 24 h 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‐related by the investigator were reported in six subjects treated with BI 1595043. The study was discontinued prematurely due to the sponsor's decision to terminate the development of BI 1595043 in all indications.

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