{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:04:06Z","timestamp":1789700646728,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Brensocatib, a competitive and reversible oral DPP1 inhibitor, at 10 and 25\u2009mg significantly reduced pulmonary exacerbation burden, and 25\u2009mg also reduced lung function decline vs. placebo in patients with non\u2010cystic fibrosis bronchiectasis, hereafter bronchiectasis, in ASPEN (NCT04594369). A population pharmacokinetic (PPK) model was developed to support brensocatib dose selection for adults and adolescents. Data from 11 clinical trials were pooled for analysis. The covariate model was developed via a stepwise approach. Clinical relevance of statistically significant covariates was assessed by simulated brensocatib exposure at steady state in various subgroups with different characteristics relative to a reference subject (healthy White male, 49\u2009years, 70\u2009kg, fasted, no concomitant medications). Covariate effects on brensocatib PK were evaluated. From 291 healthy participants and 807 patients, 11,643 brensocatib plasma concentrations were used for PPK model construction. Body weight was integrated using standard allometric scaling coefficients of 0.75 on total and intercompartment clearance (CL\/F and Q\/F) and 1.0 on central and peripheral volume of distribution (Vc\/F and Vp\/F). Statistically significant covariates included hepatic impairment, sex, race, and co\u2010medication use (strong CYP3A and Pgp modulators) on CL\/F; age on Vc\/F; food effect on Ka; and co\u2010medications (strong CYP3A and Pgp inhibitors) on relative bioavailability. Disease populations, renal impairment, and tablet formulations were not statistically significant covariates. The PPK model provided a robust fit to observed brensocatib concentration time profiles in bronchiectasis patients. No identified covariates were clinically relevant. This analysis supported brensocatib dosage of 10 and 25\u2009mg in patients with bronchiectasis \u2265\u200912\u2009years without dose adjustment.<\/jats:p>","DOI":"10.1002\/psp4.70340","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:18:41Z","timestamp":1788938321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Analysis of Brensocatib in Adult and Adolescent Patients With Non\u2010Cystic Fibrosis Bronchiectasis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-2714","authenticated-orcid":false,"given":"Helen","family":"Usansky","sequence":"first","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cammarata","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics  Schenectady New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChongHua","family":"Li","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Au Yeung","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics  Schenectady New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Teper","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8319-1335","authenticated-orcid":false,"given":"Carlos","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mange","sequence":"additional","affiliation":[{"name":"Insmed, Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0042-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31767-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01702-2020"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30504-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1053"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01127"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01147-w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-025-01550-z"},{"key":"e_1_2_9_10_1","volume-title":"Prescribing Information","author":"Brinsupri (Brensocatib)","year":"2025"},{"key":"e_1_2_9_11_1","volume-title":"EPAR\u2013Summary of Product Characteristics","author":"Brinsupri (Brensocatib)","year":"2025"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021713"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2411664"},{"key":"e_1_2_9_14_1","unstructured":"Brinsupri. Medicines and Healthcare products Regulatory Agency \u201cMHRA\u2013Summary of Product Characteristics \u201d(2026)."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1094"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-025-01614-0"},{"key":"e_1_2_9_17_1","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":"European Respiratory Journal"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.16344"},{"key":"e_1_2_9_19_1","volume-title":"M10 Bioanalytical Method Validation and Study Sample Analysis","author":"United States Food and Drug Administration","year":"2022"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_9_21_1","first-page":"225","article-title":"Estimation of Human Body Surface Area From Height and Weight","volume":"54","author":"Gehan E. A.","year":"1970","journal-title":"Cancer Chemotherapy Reports"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:36:31Z","timestamp":1789698991000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":20,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/psp4.70340"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70340","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70340"}}