{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:08:52Z","timestamp":1787317732974,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This work assessed the pharmacokinetics (PK), safety and tolerability of glasmacinal (EP395, an oral anti\u2010inflammatory macrolide with negligible antimicrobial activity in development for COPD treatment) in two healthy participant trials: \u2018first\u2010in\u2010human\u2019 (FIH) and \u2018drug\u2013drug\u2010interaction\u2019 (DDI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The FIH trial was a randomized, double\u2010blind, placebo\u2010controlled trial of single (20\u2013750\u2009mg) and multiple (120\u2013375\u2009mg daily for 28\u2009days) doses of glasmacinal. The DDI trial was an open\u2010label assessment of the effect of verapamil (moderate CYP3A4 inhibitor and P\u2010gp inhibitor) on the PK of glasmacinal, and the effect of glasmacinal on the PK of midazolam (CYP3A4 substrate) and digoxin (P\u2010gp substrate).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No SAEs or severe AEs occurred, and no AEs considered related to glasmacinal led to withdrawal. Glasmacinal was rapidly absorbed, reaching peak plasma concentrations at ~4\u2009h post\u2010dose and a terminal half\u2010life ~70\u2009h. Glasmacinal systemic exposure (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      and AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      ) was reduced by one third when administered after food (300\u2010mg single dose, parallel group comparison). Co\u2010administration of glasmacinal with verapamil increased glasmacinal exposure (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      1.70\u2010fold [90% CI: 1.52, 2.39], AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      2.41\u2010fold [90% CI: 2.18, 2.82]). Glasmacinal modestly increased exposure to midazolam (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      1.26\u2010fold [90% CI: 1.12, 1.49], AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      1.54\u2010fold [90% CI: 1.33, 1.89]) and digoxin (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      1.38\u2010fold [90% CI: 1.22, 1.81] and AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      1.37\u2010fold [90% CI: 1.26, 1.52]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Glasmacinal was well tolerated in single doses up to 750\u2009mg and repeat doses up to 375\u2009mg. Glasmacinal may be a victim of selected drugs that impact CYP3A4 and\/or P\u2010gp but is unlikely to be a perpetrator of clinically relevant DDIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70509","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:00:16Z","timestamp":1773810016000},"page":"2349-2363","source":"Crossref","is-referenced-by-count":1,"title":["Early clinical pharmacology evaluation of the novel anti\u2010inflammatory macrolide, glasmacinal (EP395): tolerability, pharmacokinetics and drug interactions"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-7075","authenticated-orcid":false,"given":"Dave","family":"Singh","sequence":"first","affiliation":[{"name":"The Medicines Evaluation Unit  Manchester UK"},{"name":"University of Manchester Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9629-8491","authenticated-orcid":false,"given":"Kate","family":"Hanrott","sequence":"additional","affiliation":[{"name":"EpiEndo Pharmaceuticals  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0945-8736","authenticated-orcid":false,"given":"Olof","family":"Breuer","sequence":"additional","affiliation":[{"name":"EpiEndo Pharmaceuticals  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bylund","sequence":"additional","affiliation":[{"name":"CTC Clinical Trial Consultants AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Schultze","sequence":"additional","affiliation":[{"name":"CTC Clinical Trial Consultants AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Norris","sequence":"additional","affiliation":[{"name":"EpiEndo Pharmaceuticals  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2017.1285677"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.03.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(20)30080\u20101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753465816682677"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31281\u20103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104623"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60953\u20102"},{"key":"e_1_2_11_9_1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD).Global strategy for diagnosis management and prevention of COPD.2024. 2025 report. 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