{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:06:54Z","timestamp":1790140014145,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inhaled corticosteroids (ICS) plus bronchodilator are recommended for the treatment of asthma. Targeting the JAK1\u2010dependent pathway may be an alternative for asthma management in patients with incomplete response to ICS. The aim of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD0449, a novel JAK1 selective inhibitor, following inhaled (dry powder, nebulized) and intravenous administration to healthy participants and patients with mild asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a randomized, single\u2010blind, placebo\u2010controlled Phase 1 study (NCT03766399) of single\u2010 and multiple\u2010ascending doses conducted using a three\u2010part design. Healthy participants and patients with mild asthma aged 18\u201355\u2009years were recruited. The study evaluated safety, tolerability, PK and PD of AZD0449. PD was measured as the effect on fractional exhaled nitric oxide (FeNO). Systemic target engagement was measured using phosphorylation of signal transducer and activator of transcription 6 (pSTAT6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 125 participants were included in the study. No drug\u2010related safety concerns emerged. Following inhaled administration, AZD0449 showed low, dose\u2010proportional, systemic exposures and elimination from plasma was partly absorption\u2010limited, suggesting lung retention and supporting once\u2010daily dosing. At the dose levels evaluated (1.2\u20135.0\u00a0mg), there was no significant anti\u2010inflammatory effect (reduction in FeNO) with AZD0449\n                      <jats:italic>vs<\/jats:italic>\n                      . placebo, following repeated dosing for 14\u2009days. Furthermore, there was no significant suppression of pSTAT6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AZD0449 was safely administered via inhalation, with low systemic exposure and lung retention. This study provides a greater understanding of inhaled dosing of small molecule JAK1 inhibitors for the treatment of asthma. No effect on PD biomarkers (FeNO and STAT6) was observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70262","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T10:58:41Z","timestamp":1756551521000},"page":"257-268","source":"Crossref","is-referenced-by-count":6,"title":["AZD0449, an inhaled JAK1 inhibitor, in healthy participants and patients with mild asthma"],"prefix":"10.1002","volume":"92","author":[{"given":"Anna","family":"Lundahl","sequence":"first","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology, Clinical Pharmacology &amp; Safety Sciences R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1200-5580","authenticated-orcid":false,"given":"Rod","family":"Hughes","sequence":"additional","affiliation":[{"name":"Research and Early Development, Respiratory and Immunology AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-9332","authenticated-orcid":false,"given":"Joachim","family":"Almquist","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology, Clinical Pharmacology &amp; Safety Sciences R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Close","sequence":"additional","affiliation":[{"name":"Research and Early Development, Respiratory and Immunology AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"M\u00e4enp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Chief Medical Office, Research &amp; Development, Patient Safety Biopharma AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Tehler","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery, Pharmaceutical Sciences R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina Jellesmark","family":"Jensen","sequence":"additional","affiliation":[{"name":"Early Respiratory and Immunology Clinical Development, BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szil\u00e1rd","family":"Nemes","sequence":"additional","affiliation":[{"name":"Early Biostats &amp; Statistical Innovation, Data Science &amp; AI, BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0915-5070","authenticated-orcid":false,"given":"Anne\u2010Kristina","family":"Mercier","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Quantitative Pharmacology, Clinical Pharmacology &amp; Safety Sciences R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zala","family":"Jevnikar","sequence":"additional","affiliation":[{"name":"Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo Forte","family":"Soto","sequence":"additional","affiliation":[{"name":"Parexel Early Phase Clinical Unit  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-7075","authenticated-orcid":false,"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Unit, Manchester University NHS Foundation Hospital Trust University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5334\/aogh.2412"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.070169"},{"key":"e_1_2_10_4_1","unstructured":"Global Initiative for Asthma.Global Strategy for Asthma Management and Prevention 2025. 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