{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:30:46Z","timestamp":1790944246729,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the efficacy, safety, and tolerability of apararenone 10\u00a0mg\/day in patients with nonalcoholic steatohepatitis (NASH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this multicenter, randomized, double\u2010blind, placebo\u2010controlled phase II study, patients received apararenone 10\u00a0mg or placebo once daily for 72\u00a0weeks. The primary efficacy end\u2010point was percent change in serum alanine aminotransferase (ALT) from baseline to 24\u00a0weeks after randomization. Secondary efficacy end\u2010points included changes in liver fibrosis markers. Adverse drug reactions (ADRs) and serum potassium levels were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010eight patients were randomly assigned to treatment (placebo, 23; apararenone, 25). The percent change in ALT at 24\u00a0weeks was \u22123.0% and \u221213.7% with placebo and apararenone, respectively (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.308). The apararenone group showed greater reductions from baseline in fibrosis markers (type IV collagen 7S and procollagen\u20103 N\u2010terminal peptide) and noninvasive tests of fibrosis (enhanced liver fibrosis score and Fibrosis\u20104 index) at all time points versus placebo. The percentage of patients with improvement of 1 point or more in fibrosis stage\/without nonalcoholic fatty liver disease activity score worsening was 41.7% with apararenone and 26.1% with placebo (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.203). Adverse drug reactions were reported in three (13.0%) and three (12.5%) patients in the placebo and apararenone groups, respectively. Serum potassium levels increased in the apararenone group during the study and decreased to near baseline after the end of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In patients with NASH, apararenone 10\u00a0mg\/day for 72\u00a0weeks was effective in decreasing ALT levels, improved multiple potential fibrosis markers, and was safe and well tolerated. Pathological findings showed anti\u2010inflammatory and antifibrotic effects of apararenone.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13695","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T17:24:55Z","timestamp":1626283495000},"page":"943-956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy and safety of apararenone (MT\u20103995) in patients with nonalcoholic steatohepatitis: A randomized controlled study"],"prefix":"10.1111","volume":"51","author":[{"given":"Takeshi","family":"Okanoue","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Saiseikai Suita Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiie","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Data Science Department Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Totsuka","sequence":"additional","affiliation":[{"name":"Clinical Research and Development II Department Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Clinical Research and Development II Department Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Kumada","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"e_1_2_9_2_1","series-title":"Evidence\u2010based clinical practice guidelines for non\u2010alcoholic fatty liver disease\/nonalcoholic steatohepatitis, Japanese Guideline 2020","author":"The Japanese Society of Gastroenterology, the Japan Society of Hepatology","year":"2020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0533-z"},{"key":"e_1_2_9_4_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) 2018 Guidance for Industry"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-3902-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05640.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27126"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.09.012"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840400411"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2020.1668926"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12794"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00419.2013"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.855"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2020.09.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-020-01963-z"},{"key":"e_1_2_9_16_1","unstructured":"K Kikkawa N Shirata M Takakuwa A Nishi T Iguchi H Munakata 2017"},{"key":"e_1_2_9_17_1","unstructured":"AbeN KatoS MurataY KikkawaK OkaK. 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