{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:08:06Z","timestamp":1779890886319,"version":"3.53.1"},"reference-count":23,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"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":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2020,11,17]]},"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis. BI 1265162 is an inhaled ENaC inhibitor with demonstrated preclinical efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three phase I trials of BI 1265162 in healthy male subjects are presented:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03349723\">NCT03349723<\/jats:ext-link>(single-rising-dose trial evaluating safety, tolerability and pharmacokinetics (PK));<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03576144\">NCT03576144<\/jats:ext-link>(multiple-rising-dose trial evaluating safety, tolerability and PK); and<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03907280\">NCT03907280<\/jats:ext-link>(absolute bioavailability trial).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BI 1265162 single doses \u22641200\u2005\u00b5g and multiple doses of 600\u2005\u00b5g were well tolerated. Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. One subject discontinued from trial medication on day 7 (asymptomatic hyperkalaemia adverse event; recovered day 8). One subject experienced a serious adverse event (neuropathia vestibularis) leading to hospitalisation and missed one of the four dosing periods. Both events were not considered to be drug-related and subjects recovered. BI 1265162 displayed dose-proportional, time-independent PK; maximum accumulation was 1.6-fold; calculated effective elimination half-life was 3.6\u20138.7\u2005h over the dose ranges tested. Renal excretion was not a major drug elimination route. Oral and inhaled dosing (\u00b1activated oral charcoal) absolute bioavailability was 0.50% and \u223c40%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BI 1265162 single or multiple doses up to 6.5\u2005days were well tolerated. Systemic exposures mainly represent drug absorbed through the lungs and not the gastrointestinal tract, with \u223c40% of the inhaled dose reaching the systemic circulation. Accumulation was minimal. Twice-daily dosing is supported for future development.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.00447-2020","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T19:29:44Z","timestamp":1607628584000},"page":"00447-2020","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy 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