{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:40:39Z","timestamp":1788435639155,"version":"build-2803163510"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dotinurad, a novel selective urate reabsorption inhibitor (SURI) that has a future potential for the treatment of hyperuricemia, reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). We evaluated the efficacy and safety of dotinurad in hyperuricemic Japanese patients with or without gout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study design was an exploratory, early phase 2 study that ran for 8\u00a0weeks. It was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, and performed in a dose escalation manner. There were four study arms consisting of dotinurad 1, 2, or 4\u00a0mg, and placebo. The primary endpoint was the percent change in serum uric acid level from the baseline to the final visit. The secondary endpoint was the percentage of patients achieving a serum uric acid level\u2009\u2264\u20096.0\u00a0mg\/dL at the final visit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 80 hyperuricemic patients with or without gout were enrolled and randomly assigned to the dotinurad or placebo groups. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 1, 2, 4\u00a0mg, and placebo groups was 37.03%, 50.91%, 64.37%, and 0.85%, respectively. The percentages of patients achieving a serum uric acid level\u2009\u2264\u20096.0\u00a0mg\/dL at the final visit in each group were 75.0%, 89.5%, 95.2%, and none, respectively. The incidence of adverse events was comparable among all groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dotinurad has a substantial serum uric acid lowering effect in patients with hyperuricemia. No serious adverse event was found.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                    <jats:p>NCT02344862<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10157-019-01802-w","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T11:29:59Z","timestamp":1576495799000},"page":"44-52","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical efficacy and safety of dotinurad, a novel selective urate reabsorption inhibitor, in Japanese hyperuricemic patients with or without gout: an exploratory, randomized, multicenter, double-blind, placebo-controlled, parallel-group early phase 2 study"],"prefix":"10.1007","volume":"24","author":[{"given":"Tatsuo","family":"Hosoya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomitsu","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Fushimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,21]]},"reference":[{"key":"1802_CR1","unstructured":"Japanese Society of Gout and Uric and Nucleic Acids. Guideline for the management of hyperuricemia and gout. 3rd ed. 2018. pp. 18\u201323, 95\u20138."},{"key":"1802_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1159\/000355639","volume":"126","author":"A Toda","year":"2014","unstructured":"Toda A, Ishizaka Y, Tani M, Yamakado M. Hyperuricemia is a significant risk factor for the onset of chronic kidney disease. Nephron Clin Pract. 2014;126:33\u20138.","journal-title":"Nephron Clin Pract"},{"key":"1802_CR3","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/hr.2014.75","volume":"37","author":"M Kuwabara","year":"2014","unstructured":"Kuwabara M, Niwa K, Nishi Y, et al. Relationship between serum uric acid levels and hypertension among Japanese individuals not treated for hyperuricemia and hypertension. Hypertens Res. 2014;37:785\u20139.","journal-title":"Hypertens Res"},{"key":"1802_CR4","doi-asserted-by":"publisher","first-page":"e56864","DOI":"10.1371\/journal.pone.0056864","volume":"8","author":"Q Lv","year":"2013","unstructured":"Lv Q, Meng XF, He FF, et al. High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS ONE. 2013;8:e56864.","journal-title":"PLoS ONE"},{"key":"1802_CR5","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1080\/15257770.2011.596496","volume":"30","author":"H Yamanaka","year":"2011","unstructured":"Yamanaka H, Japanese Society of Gout and Nucleic Acid Metabolism. Japanese guideline for the management of hyperuricemia and gout: second edition. 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Am J Kidney Dis. 2009;53:982\u201392.","journal-title":"Am J Kidney Dis"}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01802-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10157-019-01802-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01802-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T23:09:10Z","timestamp":1605827350000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10157-019-01802-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,21]]},"references-count":14,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["1802"],"URL":"https:\/\/doi.org\/10.1007\/s10157-019-01802-w","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,21]]},"assertion":[{"value":"28 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Fuji Yakuhin Co., Ltd. (Fuji) the manufacturer of dotinurad sponsored this study. TH was advisor to Fuji regarding this study and received consultant and manuscript fees. The other authors were employees of Fuji.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study protocol and informed consent document were reviewed and approved by an institutional review board (Nakameguro Atlas Clinic; Tokyo, Japan). Informed consent was obtained from all individual participants included in the study. The tests were conducted in compliance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, Good Clinical Practice guidelines, and other regulatory requirements to be applied. The information of this study was registered with ClinicalTrials.gov (ClinicalTrials.gov number: NCT02344862).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}