{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:07Z","timestamp":1787013907268,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aberrantly controlled activation of the complement system contributes to inflammatory diseases. Safety, tolerability, and pharmacokinetics of single\u2010ascending doses of ACT\u20101014\u20106470, a novel orally available complement factor 5a receptor 1 antagonist, were assessed in a randomized, double\u2010blind, placebo\u2010controlled Phase 1 study. Six ACT\u20101014\u20106470 doses (0.5\u2013200\u2009mg) were selected after predictions from a Complex Dedrick plot. In each group, ACT\u20101014\u20106470 or matching placebo was administered to six and two healthy male individuals under fed conditions, respectively, including a cross\u2010over part with 10\u2009mg administered also under fasted conditions. Pharmacokinetic blood sampling and safety assessments (adverse events, clinical laboratory, vital signs, 12\u2010lead electrocardiogram, and QT telemetry) were performed. ACT\u20101014\u20106470 was absorbed with a time to maximum plasma concentration (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) of 3\u2009h across dose levels and eliminated with a terminal half\u2010life of 30\u201346\u2009h at doses \u2265 2.5\u2009mg. Exposure increased approximately dose proportionally. Under fed compared to fasted conditions, ACT\u20101014\u20106470 exposure was 2.2\u2010fold higher and\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    delayed by 1.5\u2009h. Pharmacokinetic modelling predicted that twice\u2010daily oral administration is warranted in a subsequent multiple\u2010dose study. No clinically relevant findings were observed in safety assessments. ACT\u20101014\u20106470 was well tolerated at all doses and could provide a novel therapy with more patient\u2010friendly administration route compared to biologicals.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.13756","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T23:14:47Z","timestamp":1653088487000},"page":"114-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["First\u2010in\u2010human study with ACT\u20101014\u20106470, a novel oral complement factor 5a receptor 1 (C5aR1) antagonist, supported by pharmacokinetic predictions from animals to patients"],"prefix":"10.1111","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9308-5853","authenticated-orcid":false,"given":"Marion","family":"Anliker\u2010Ort","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil 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