{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T02:40:50Z","timestamp":1770086450215,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/Introduction<\/jats:title>\n                    <jats:p>Diabetic polyneuropathy (DPN) is common in patients with diabetes. Its symptoms include pain, numbness, and impaired neurosensory function. ONO\u20102910 promotes Schwann cell differentiation and is being developed for DPN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This Phase IIa randomized controlled trial evaluated the effectiveness and safety of ONO\u20102910 in Japanese patients with type 2 diabetes and DPN. Patients were randomized to ONO\u20102910 (300\u2009mg\/day) or placebo, once daily, for 12\u2009weeks. The primary endpoints were the changes in the sum scores for numbness and tingling (modified Toronto Clinical Neuropathy Scores [mTCNS]) and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The ONO\u20102910 and placebo groups comprised 76 (safety: 77 patients) and 77 patients, respectively. The mean (standard deviation) age and time since DPN diagnosis were 62.6 (8.48) and 4.89 (5.662) years, respectively. The least\u2010squares mean (LSM) change in mTCNS sum scores for numbness and tingling at 12\u2009weeks was \u22121.0 in both groups (LSM difference: 0.0; 95% confidence interval \u22120.4 to 0.4). The LSM changes in the mTCNS total scores were \u22122.6 (0.64) and \u22122.3 (0.67) in the ONO\u20102910 and placebo groups, respectively. There were no marked changes in nerve function and nerve conduction velocities in the ONO\u20102910 and placebo groups. Treatment\u2010emergent adverse events (TEAEs) occurred in 37 (48.1%) and 39 (50.6%) patients in the ONO\u20102910 and placebo groups, respectively. TEAEs in \u22652 patients in the ONO\u20102910 group were nasopharyngitis (5 patients), diarrhea (3 patients), nausea (2 patients), and eczema (2\u00a0patients).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ONO\u20102910 was generally well\u2010tolerated in Japanese patients with DPN. There were no obvious improvements in DPN symptoms or neurosensory function among patients who received ONO\u20102910 versus placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registry<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Japan Primary Registries Network<\/jats:italic>\n                      jRCT2061210008\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70193","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:35:46Z","timestamp":1765978546000},"page":"310-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the effectiveness and safety of\n                    <scp>ONO<\/scp>\n                    \u20102910 for the treatment of diabetic polyneuropathy: An early Phase\n                    <scp>IIa<\/scp>\n                    , multicenter, randomized, placebo\u2010controlled, double\u2010blind study in Japanese patients"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1180-5982","authenticated-orcid":false,"given":"Yukiko","family":"Onishi","sequence":"first","affiliation":[{"name":"Division of Diabetes and Metabolism The Institute of Medical Science, Asahi Life Foundation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Osonoi","sequence":"additional","affiliation":[{"name":"Nakakinen Clinic  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Nagoya Ekisaikai Hospital  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichiro","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Ono Pharmaceutical Co., Ltd.  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-1999","authenticated-orcid":false,"given":"Yoshimasa","family":"Aso","sequence":"additional","affiliation":[{"name":"Dokkyo Medical University Hospital  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Division of Neurology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Division of Diabetes Department of Internal Medicine Aichi Medical University School of Medicine  Nagakute Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-6916","authenticated-orcid":false,"given":"Jiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Diabetes Department of Internal Medicine Aichi Medical University School of Medicine  Nagakute Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.01.048"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14469"},{"key":"e_1_2_9_4_1","article-title":"Diabetic polyneuropathy in type 1 and type 2 diabetes mellitus: A cross\u2010sectional study","volume":"14","author":"Hindi E","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-023-00678-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db2022-01"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13306"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc05-2370"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5383797"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12890"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2008.02490.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041360"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00425.x"},{"key":"e_1_2_9_14_1","unstructured":"NakanishiN KonemuraT NakayamaK et\u00a0al.Promoting Schwann cell differentiation attenuates diabetic neuropathy in STZ\u2010induced diabetic rat models. Abstract C\u20101\u20106. Presented at the 147th Kinki Branch Meeting of the Japanese Pharmacological Society June 2025."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2009.02667.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.08.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-2799"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05846-8"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdi.70193","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:38:23Z","timestamp":1770039503000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.70193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/jdi.70193"],"URL":"https:\/\/doi.org\/10.1111\/jdi.70193","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"assertion":[{"value":"2025-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}