{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:03:28Z","timestamp":1784811808326,"version":"3.55.0"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002975","name":"Dainippon Sumitomo Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study examined the safety, tolerability, and pharmacokinetics (PK) of napabucasin in healthy Asian and non\u2010Asian participants and investigated the potential for QT\/QTc interval prolongation. This five\u2010part (A\u2013E) study proceeded in a stepwise manner, unless stopping criteria were met. Parts A\u2013D were randomized, double\u2010blind, placebo\u2010controlled, and included healthy Asian male and female and non\u2010Asian male participants. PK parameters were measured following single\u2010dose napabucasin (80\u20131200\u00a0mg) in the fasted or fed state (Part D). Potential QT\/QTc interval prolongation was assessed using digital 12\u2010lead electrocardiogram (Parts B and C). Part E was open\u2010label, and examined the PK of single\u2010dose napabucasin (240\u2013720\u00a0mg) in healthy non\u2010Asian males. Safety and tolerability were measured in Parts A\u2013E. Changes from baseline in the Fridericia\u2010corrected QT interval (\u0394QTcF) and other electrocardiogram parameters were analyzed using a linear mixed\u2010effects model. Napabucasin was well\u2010tolerated across the study (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a070), and no serious adverse events or significant safety issues were reported when administered with or without food. The most frequent treatment\u2010emergent adverse events were diarrhea and abdominal pain, and these were mild in severity. No prolongation of the QTcF interval was reported following single\u2010dose napabucasin (240\u20131200\u00a0mg) and changes in other cardiac parameters were negligible. The PK profile of napabucasin was consistent with earlier studies. Single\u2010dose napabucasin was tolerated in healthy male and female participants, and no significant safety (including no QTcF prolongation) or tolerability issues were identified, irrespective of food intake. Clinical studies of napabucasin in advanced cancers are ongoing.\n                  <\/jats:p>","DOI":"10.1002\/prp2.874","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T09:45:21Z","timestamp":1633859121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of a reactive oxygen species generator, napabucasin (BBI608), on tolerability, safety, pharmacokinetics, and QT\/QTc interval in healthy volunteers"],"prefix":"10.1002","volume":"9","author":[{"given":"Naoto","family":"Noda","sequence":"first","affiliation":[{"name":"Clinical Research Drug Development Division Sumitomo Dainippon Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Takagaki","sequence":"additional","affiliation":[{"name":"Clinical Research Drug Development Division Sumitomo Dainippon Pharma Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Yodo","sequence":"additional","affiliation":[{"name":"Data Science Drug Development Division Sumitomo Dainippon Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzo","family":"Horibuchi","sequence":"additional","affiliation":[{"name":"Oncology Clinical Development Unit Sumitomo Dainippon Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Iino","sequence":"additional","affiliation":[{"name":"Oncology Clinical Development Unit Sumitomo Dainippon Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Matsuki","sequence":"additional","affiliation":[{"name":"Fukuoka Mirai Hospital SOUSEIKAI  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Ogama","sequence":"additional","affiliation":[{"name":"Sumida Hospital SOUSEIKAI  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Kakuyama","sequence":"additional","affiliation":[{"name":"Clinical Research Drug Development Division Sumitomo Dainippon Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/ace.2018.08.01"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyv002"},{"key":"e_1_2_10_4_1","unstructured":"Global Cancer Observatory.GLOBOCAN 2018: Japan factsheet. 2018. Accessed April 6 2021.https:\/\/gco.iarc.fr\/today\/data\/factsheets\/populations\/392\u2010japan\u2010fact\u2010sheets.pdf."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-1242"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-15-0207-T"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0302"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.2542"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04059-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11561"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.874","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.874","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:37:32Z","timestamp":1784810252000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/prp2.874"],"URL":"https:\/\/doi.org\/10.1002\/prp2.874","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"2021-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00874"}}