{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:16:52Z","timestamp":1784233012828,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Bronchiectasis patients face an unmet need for treatment options that reduce inflammation. Cathepsin C inhibition is expected to achieve this by reducing the activation of neutrophil\u2010derived serine proteases. Here, we present safety and pharmacokinetic (PK) data from a Phase I trial evaluating the novel cathepsin C inhibitor BI 1291583 in healthy Japanese male subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group study investigated BI 1291583 in healthy Japanese male subjects (jRCT2071210111) and consisted of a single\u2010rising\u2010dose (SRD) part and a multiple\u2010dose (MD) part. The primary endpoint was the percentage of subjects with drug\u2010related treatment\u2010emergent adverse events (AEs). Secondary PK endpoints (SRD: AUC<jats:sub>0\u2010\u221e<\/jats:sub> and C<jats:sub>max<\/jats:sub>; MD: AUC<jats:sub>\u03c4,1<\/jats:sub> and C<jats:sub>max,1<\/jats:sub> after first dose and AUC<jats:sub>\u03c4,ss<\/jats:sub> and C<jats:sub>max,ss<\/jats:sub> after last dose), as well as further safety and PK endpoints, were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 36 subjects (<jats:italic>n\u2009=<\/jats:italic>\u00a024 for SRD part; <jats:italic>n\u2009=<\/jats:italic>\u00a012 for MD part) entered this Phase I trial. BI 1291583 was safe and well tolerated across the doses tested. All AEs were of mild intensity, with no drug\u2010related treatment\u2010emergent AEs, deaths, serious AEs or AEs of special interest reported in either part of the trial. Following both SRD and MD administration, BI 1291583 was readily absorbed, and PK was supraproportional over the doses assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results show that BI 1291583 has an appropriate benefit\u2013risk ratio for Japanese patients, with no safety or exposure concerns at the doses studied. Japanese patients with bronchiectasis can be safely integrated into future global clinical trials of BI 1291583, with no dose adjustment required.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16249","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T23:15:12Z","timestamp":1726787712000},"page":"199-209","source":"Crossref","is-referenced-by-count":3,"title":["A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects"],"prefix":"10.1111","volume":"91","author":[{"given":"Yusuke","family":"Tadayasu","sequence":"first","affiliation":[{"name":"Nippon Boehringer Ingelheim Co. Ltd.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Sarubbi","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  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Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Sauter","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuzo","family":"Hanada","sequence":"additional","affiliation":[{"name":"SOUSEIKAI Sumida Hospital  Tokyo 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