{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:33:50Z","timestamp":1761060830484,"version":"3.37.3"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical Co., Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We examined the efficacy, safety, and tolerability of ONO\u20104474 in Japanese patients with osteoarthritis (OA) of the knee. In this multicenter, placebo\u2010controlled, randomized, double\u2010blind, parallel\u2010group comparative study, patients with moderate to severe OA who were refractory to nonsteroidal anti\u2010inflammatory drugs were orally administered 100 mg of ONO\u20104474 twice daily for 28 days. The primary end point was knee pain during walking, assessed by visual analog scale over 24 hours (VAS<jats:sub>24<\/jats:sub>). Treatment\u2010emergent adverse events (TEAEs) and adverse drug reactions were reported for safety. In total, 110 patients were randomized (1:1) to receive placebo or ONO\u20104474. The mean (standard deviation) change in VAS<jats:sub>24<\/jats:sub> scores at week 4 was \u221226.9 (25.0)\u00a0mm in the ONO\u20104474 group and \u221219.5 (19.6)\u00a0mm in the placebo group. The difference (ONO\u20104474 group \u2212 placebo group) in posterior mean change in VAS<jats:sub>24<\/jats:sub> at week 4 was \u22125.8 (posterior standard deviation, 4.4; 95% confidence interval, \u221214.3 to 2.8)\u00a0mm. TEAEs were reported in 41.8% of patients in the ONO\u20104474 group and 18.2% of patients in the placebo group. The most common TEAEs in the ONO\u20104474 group related to the musculoskeletal system and the peripheral and central nervous systems were myalgia (7.3%), arthralgia (5.5%), dizziness (3.6%), and hypoesthesia (3.6%). Four patients from the ONO\u20104474 group and 1 patient from the placebo group discontinued treatment because of AEs; however, none were judged to be serious, and all patients recovered or were recovering after discontinuation. ONO\u20104474 is a novel tropomyosin receptor kinase inhibitor that has an analgesic effect in patients with OA.<\/jats:p>","DOI":"10.1002\/jcph.1470","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T07:54:53Z","timestamp":1562572493000},"page":"28-36","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy, Safety, and Tolerability of ONO\u20104474, an Orally Available Pan\u2010Tropomyosin Receptor Kinase Inhibitor, in Japanese Patients With Moderate to Severe Osteoarthritis of the Knee: A Randomized, Placebo\u2010Controlled, Double\u2010Blind, Parallel\u2010Group Comparative Study"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-4035","authenticated-orcid":false,"given":"Naoki","family":"Ishiguro","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School &amp; Faculty of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shusuke","family":"Oyama","sequence":"additional","affiliation":[{"name":"Data Science Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryunosuke","family":"Higashi","sequence":"additional","affiliation":[{"name":"Translational Science Translational Medicine Center Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunio","family":"Yanagida","sequence":"additional","affiliation":[{"name":"Translational Science Translational Medicine Center Ono Pharmaceutical Co., Ltd.  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