{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:57:29Z","timestamp":1790621849139,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"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":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (PK), food\u2010effect (FE) and pharmacodynamics (PD) of an oral tyrosine kinase\u20102 (TYK2)\/Janus kinase\u20101 (JAK1) inhibitor, SDC\u20101801, in healthy adult participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This first\u2010in\u2010human study randomized 95 male and female participants. Parts one and two were double\u2010blind, placebo\u2010controlled escalation designs, investigating single (5, 10, 30, 75, 150\u2009mg) and multiple (30, 100, 75, 140\u2009mg\/day) doses of SDC\u20101801 or matching placebo. Part three evaluated the FE of 75\u2009mg SDC\u20101801 in an open\u2010label, crossover design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were no deaths or treatment\u2010related serious adverse events (AEs) following SDC\u20101801, up to 150\u2009mg; no treatment\u2010emergent AEs (TEAEs) were severe with non\u2010related headache most frequently reported. PK showed low to moderate variability and no consistent dose\u2010exposure relationship;\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      occurred 3\u20135\u2009h post\u2010dose with a geometric mean (GM)\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      of 15.2\u201327.0\u2009h. Bioavailability appeared solubility limited, with lower exposure from the higher strength capsule and modestly higher exposure in the fed state. No safety stopping criteria were met. PD assessments demonstrated anti\u2010inflammatory activity, with IFN\u2010gamma induced protein\u201010 (IP\u201010), high sensitivity C reactive protein (hsCRP), and signal transducer and activator of transcription (STAT3\/5) phosphorylation reductions with increasing exposure giving greater inhibition. At the highest exposure, there was a clear reduction of IP\u201010 levels at pre\u2010dose on day 9, which rebounded following drug withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SDC\u20101801 was well tolerated to 150\u2009mg; all TEAEs were mild or moderate, with unrelated headache most frequently reported. The PK profile supports the potential for a once\u2010 or twice\u2010daily regimen, with evidence of target engagement for both TYK2 and JAK1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70642","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:55:08Z","timestamp":1782111308000},"page":"3513-3526","source":"Crossref","is-referenced-by-count":0,"title":["First\u2010in\u2010human, phase I, randomized, safety, pharmacokinetic, food\u2010effect and pharmacodynamic study of a tyrosine kinase 2\/Janus kinase 1 inhibitor, SDC\u20101801"],"prefix":"10.1002","volume":"92","author":[{"given":"Chris","family":"Brearley","sequence":"first","affiliation":[{"name":"tranScrip Ltd  Wokingham Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Francis","sequence":"additional","affiliation":[{"name":"Emeritus Research, (Employed by Nucleus Network at the Time of the Study)  Melbourne Victoria 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