{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:29:08Z","timestamp":1784842148619,"version":"3.55.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"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><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Dotinurad, a novel selective urate reabsorption inhibitor (SURI), reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1) for the treatment of hyperuricemia with or without gout. We confirmed the serum uric acid lowering effect and safety of dotinurad.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a confirmatory, 12-week, randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose escalation, late phase 2 study. The study arms were dotinurad 0.5, 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><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The study drugs were administered to 200 Japanese hyperuricemic patients with or without gout. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 0.5, 1, 2, and 4\u00a0mg groups and the placebo group was 21.81%, 33.77%, 42.66%, 61.09%, and\u2009\u2212\u20092.83%, respectively. The percentage of patients achieving a serum uric acid level\u2009\u2264\u20096.0\u00a0mg\/dL at the final visit in each group was 23.1%, 65.9%, 74.4%, 100%, and none, respectively. Regarding safety, the incidence of adverse events did not increase with dose escalation in the dotinurad groups. No significant differences were observed in the incidence of gouty arthritis in each group.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The serum uric acid lowering effect and safety of dotinurad were confirmed in hyperuricemic patients with or without gout.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n<jats:p>NCT02416167<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s10157-019-01818-2","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T22:02:23Z","timestamp":1575324143000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Clinical efficacy and safety of dotinurad, a novel selective urate reabsorption inhibitor, in Japanese hyperuricemic patients with or without gout: randomized, multicenter, double-blind, placebo-controlled, parallel-group, confirmatory 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":[[2019,12,3]]},"reference":[{"key":"1818_CR1","unstructured":"Japanese Society of Gout and Uric & Nucleic Acids: guideline for the management of hyperuricemia and gout, 3rd edn. 2018. p. 18\u201323, 95\u20138, 118\u201321, 122\u20134."},{"key":"1818_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":"1818_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":"1818_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. 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Nucleosides Nucleotides Nucleic Acids. 2011; 30:1018\u201329.","DOI":"10.1080\/15257770.2011.596496"},{"key":"1818_CR8","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1177\/106002809302700317","volume":"27","author":"F Arellano","year":"1993","unstructured":"Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother. 1993;27:337\u201343.","journal-title":"Ann Pharmacother."},{"key":"1818_CR9","doi-asserted-by":"crossref","unstructured":"Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76:47\u201356.","DOI":"10.1016\/0002-9343(84)90743-5"},{"issue":"suppl 2","key":"1818_CR10","doi-asserted-by":"publisher","first-page":"ii15","DOI":"10.1093\/rheumatology\/kep088","volume":"48","author":"N. L. Edwards","year":"2009","unstructured":"Edwards NL. Febuxostat: a new treatment for hyperuricaemia in gout. 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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\/s10157-019-01818-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10157-019-01818-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01818-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:03:23Z","timestamp":1606853003000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10157-019-01818-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,3]]},"references-count":18,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["1818"],"URL":"https:\/\/doi.org\/10.1007\/s10157-019-01818-2","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,3]]},"assertion":[{"value":"16 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 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":"The study protocol and informed consent document were reviewed and approved by an institutional review board (Shinagawa East One Medical Clinic, Tokyo, Japan; Nakameguro Atlas Clinic, Tokyo, Japan; Asai Dermatology Clinic, Kanagawa, 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: NCT02416167).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"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":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}