{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:03:14Z","timestamp":1791421394493,"version":"4.3.3"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brensocatib, an investigational first\u2010in\u2010class, small\u2010molecule, orally bioavailable, selective, and reversible dipeptidyl peptidase 1 inhibitor that blocks activation of neutrophil serine proteases, is currently under clinical development for the treatment of bronchiectasis and other chronic inflammatory diseases. In a 2\u2010part phase 1 study, the safety, tolerability, and pharmacokinetics of brensocatib were evaluated in healthy Japanese and White adults. In part A, participants received single and multiple once\u2010daily doses of brensocatib (10, 25, or 40\u00a0mg) or placebo after an overnight fast. In part B, participants received a single oral dose of brensocatib 40\u00a0mg on days 1 and 8, with or without food in a crossover fashion. Following a single dose and at steady state, brensocatib exposure was dose dependent, with low to moderate interindividual variability; systemic exposure between Japanese and White participants was similar. Elimination half\u2010life of brensocatib ranged from 22 to 28 hours, resulting in \u22482\u2010fold accumulation in maximum plasma concentration and area under the plasma concentration\u2013time curve at steady state. In both ethnic groups, the presence of food slightly delayed brensocatib absorption with time to maximum plasma concentration increased by 0.7 to 1.7 hours, but it had no significant effect on brensocatib exposure (maximum plasma concentration and area under the plasma concentration\u2013time curve). Brensocatib was well tolerated in Japanese and White participants. The most frequently reported treatment\u2010emergent adverse events were headache and skin exfoliation. No clinically significant vital signs, laboratory abnormalities, or evidence of renal toxicity were observed. The results from this study demonstrate that brensocatib can be administered with or without food and that dose adjustment is unnecessary for Japanese patients when receiving brensocatib treatment.<\/jats:p>","DOI":"10.1002\/cpdd.1094","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T05:29:36Z","timestamp":1649741376000},"page":"832-842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Safety, Tolerability, and Pharmacokinetic Evaluation of Single and Multiple Doses of the Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Healthy Japanese and White Adults"],"prefix":"10.1002","volume":"11","author":[{"given":"Helen","family":"Usansky","sequence":"first","affiliation":[{"name":"Insmed Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Yoon","sequence":"additional","affiliation":[{"name":"Adventist Health Glendale USC Verdugo Hills Hospital, Glendale Memorial Hospital and Health Center  Glendale California 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"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"Insmed Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Insmed Incorporated  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0638-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1479972317709649"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021713"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-017-0691-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2009.091041"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.04004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13398"},{"key":"e_1_2_9_9_1","first-page":"50","article-title":"European Respiratory Society guidelines for the management of adult bronchiectasis","author":"Polverino E","year":"2017","journal-title":"Eur Respir J"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1053"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002733"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01127"},{"key":"e_1_2_9_13_1","first-page":"PA3977","article-title":"Effect of CYP3A4 inhibitors verapamil and itraconazole on the pharmacokinetics of AZD7986, and oral DPP1 inhibitor","volume":"50","author":"Gardiner P","year":"2017","journal-title":"Euro Respir J"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.141"},{"issue":"40","key":"e_1_2_9_15_1","article-title":"Ethnopharmacology","volume":"105","author":"Munoz C","year":"2005","journal-title":"Am J Nurs"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1841"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T05:56:49Z","timestamp":1692856609000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,11]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/cpdd.1094"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1094","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,11]]},"assertion":[{"value":"2021-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}