{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:12:21Z","timestamp":1790381541015,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020483","name":"Insmed","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 1, multicentre, open\u2010label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to &lt;90, 30 to &lt;60 and 15 to &lt;30\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>, respectively) or normal renal function (\u226590\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>) received a single oral 25\u2010mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14\u2010day study period. PK parameters were derived using noncompartmental methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half\u2010life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single\u2010dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1\u00a0h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment\u2010emergent adverse events were reported during the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Single\u2010dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration Number<\/jats:title><jats:p>NCT05673603.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16344","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T08:48:55Z","timestamp":1732265335000},"page":"1191-1197","source":"Crossref","is-referenced-by-count":6,"title":["The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration"],"prefix":"10.1111","volume":"91","author":[{"given":"Sam Au","family":"Yeung","sequence":"first","affiliation":[{"name":"Insmed Incorporated  Bridgewater NJ United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Stein","sequence":"additional","affiliation":[{"name":"Insmed Incorporated  Bridgewater NJ United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Marbury","sequence":"additional","affiliation":[{"name":"Orlando Clinical Research Center  Orlando FL United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Usansky","sequence":"additional","affiliation":[{"name":"Insmed Incorporated  Bridgewater NJ United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.10.055"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01899\u20102015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arbr.2020.11.010"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/642503"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(18)30053\u20105"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100041\u20101730891"},{"key":"e_1_2_10_8_1","volume-title":"Chronic obstructive pulmonary diseases","author":"Chalmers JD","year":"2024"},{"key":"e_1_2_10_9_1","first-page":"PA3977","article-title":"Effect of CYP3A4 inhibitors verapamil and itraconazole on the pharmacokinetics of AZD7986, an oral DPP1 inhibitor","volume":"50","author":"Gardiner P","year":"2017","journal-title":"Eur Respir J"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1053"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1094"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021713"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010022\u201001147\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2010.02.337"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"issue":"1","key":"e_1_2_10_16_1","first-page":"45","article-title":"ICH harmonized tripartite guideline: guideline for good clinical practice","volume":"47","author":"International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use","year":"2001","journal-title":"J Postgrad Med"},{"issue":"2","key":"e_1_2_10_17_1","first-page":"S289","article-title":"The concise guide to PHARMACOLOGY 2023\/24: enzymes","volume":"180","author":"Alexander SPH","year":"2023","journal-title":"Br J Pharmacol"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T09:43:10Z","timestamp":1744450990000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/bcp.16344"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16344","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]}}}