{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T12:25:38Z","timestamp":1774268738206,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022274","name":"Daiichi Sankyo Europe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Valemetostat tosylate (valemetostat) is a dual inhibitor of enhancer of zeste homolog (EZH)2 and EZH1, approved in Japan for the treatment of relapsed or refractory peripheral T\u2010cell lymphoma, including adult T\u2010cell leukemia\/lymphoma, and globally under investigation for the treatment of non\u2010Hodgkin lymphomas and solid tumors. Valemetostat is a substrate of cytochrome P450 3A (CYP3A) and P\u2010glycoprotein (P\u2010gp) in\u00a0vitro. This phase 1, open\u2010label, single\u2010sequence crossover study assessed the effect of repeated oral doses of rifampicin, a strong CYP3A and P\u2010gp inducer, on the pharmacokinetics (PK) of valemetostat in healthy Japanese participants. In this trial, 20 participants received two doses of valemetostat 200\u2009mg, once alone and once after repeated daily doses of rifampicin 600\u2009mg. Coadministration with rifampicin decreased the maximum plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) and area under the plasma concentration\u2013time curve extrapolated to infinity (AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ) of total valemetostat. The geometric least\u2010squares mean ratios (GMR, test\/reference) for\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    were 0.417 [90% confidence interval (CI), 0.319\u20130.545] and 0.286 [90% CI, 0.225\u20130.364], respectively.\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of CALZ\u20101809a (a major valemetostat oxidative metabolite) increased (GMR, 1.287 [90% CI, 1.036\u20131.600]), while the AUC\n                    <jats:sub>inf<\/jats:sub>\n                    decreased (GMR, 0.713 [90% CI, 0.573\u20130.886]). No treatment\u2010related or Grade \u2265\u20092 adverse events were reported. These results showed that valemetostat exposure was reduced upon coadministration of rifampicin, suggesting that concomitant use of valemetostat with strong CYP3A and P\u2010gp inducers should be avoided.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Japan Registry: jRCT2080225242\n                  <\/jats:p>","DOI":"10.1111\/cts.70279","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T12:38:01Z","timestamp":1751891881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Rifampicin on the Pharmacokinetics of Valemetostat and Its Primary Metabolite: A Phase 1 Study in Healthy Participants"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5608-5254","authenticated-orcid":false,"given":"Masaya","family":"Tachibana","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-7120","authenticated-orcid":false,"given":"Shunji","family":"Matsuki","sequence":"additional","affiliation":[{"name":"Fukuoka Mirai Hospital  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akifumi","family":"Kurata","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-2956","authenticated-orcid":false,"given":"Masato","family":"Fukae","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  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