{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:21Z","timestamp":1792384881096,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aim<\/jats:title>\n To characterise the pharmacokinetics (PKs) and safety of BM2216 sustained\u2010release (SR) tablets after single\u2010dose oral administration under fasted\/fed conditions in healthy participants, assess the effect of food and dose proportionality, and compare the single and multiple\u2010dose PK of BM2216 SR tablets with mirogabalin besylate tablets to estimate the bioavailability.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n This was a single\u2010centre, randomised, open\u2010label, phase I study conducted in healthy adult participants aged 18\u201345\u2009years old, consisting of three parts: Part 1 (Food effect and single\u2010dose PK comparison): 18 participants were 1:1:1 randomised into three sequences: (1) 16.5\u2009mg BM2216 (fasting 18:00, QD); (2) 15\u2009mg mirogabalin besylate tablets (fasting 18:00\/next\u2010day 6:00, 7.5\u2009mg\/dose); (3) 16.5\u2009mg BM2216 (post\u2010high\u2010fat dinner, QD). A 3\u2010period crossover design with a 72\u2009h washout period; Part 2 (Single\u2010dose proportionality): 32 participants were equally assigned to four groups, receiving BM2216 SR tablets (5.5, 11, 16.5, or 33\u2009mg) 30\u2009min post\u2010standard meal, respectively; Part 3 (Multiple\u2010dose PK comparison): 16 participants were 1:1 randomised into two sequences: (1) BM2216 (post\u2010dinner, 16.5\u2009mg QD, four consecutive days); (2) 15\u2009mg mirogabalin besylate tablets (fasting 18:00\/next\u2010day 6:00, 7.5\u2009mg\/dose, four consecutive days). Crossover was conducted with a 72\u2009h washout period. PK parameters were calculated and compared using non\u2010compartmental analysis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The most common adverse events (AEs) were dizziness (15.6%), increased bile acids (12.5%) and vertigo (12.5%). Dizziness appeared in both the 16.5 and 33\u2009mg dose groups, while vertigo was only seen in the 33\u2009mg group, no serious AEs occurred. Single postprandial doses (5.5\u201333\u2009mg) exhibited linear PKs:\n T<\/jats:italic>\n max<\/jats:sub>\n median 3.00\u20135.02\u2009h, with dose\u2010proportional increases in\n C<\/jats:italic>\n max<\/jats:sub>\n , AUC\n \n 0\u2212\n t<\/jats:italic>\n <\/jats:sub>\n and AUC\n 0\u2212\u221e<\/jats:sub>\n . Multiple doses (16.5\u2009mg QD, 4\u2009days) had\n T<\/jats:italic>\n max<\/jats:sub>\n ,\n ss<\/jats:sub>\n median 5.996\u2009h,\n t<\/jats:italic>\n 1\/2,ss<\/jats:sub>\n mean 3.8075\u2009h; The RAC\n \n ,\n C<\/jats:italic>\n max\n <\/jats:sub>\n and RAC\n ,AUC<\/jats:sub>\n were 0.9965 and 1.0150, indicating no accumulation; high\u2010fat meal significantly extending\n T<\/jats:italic>\n 1\/2<\/jats:sub>\n by 3.5\u2009h, increasing\n C<\/jats:italic>\n max<\/jats:sub>\n by 16%, delaying\n T<\/jats:italic>\n max<\/jats:sub>\n by 3\u2009h and raising AUC by 30%. Postprandial BM2216 (16.5\u2009mg) and fasting mirogabalin besylate (15\u2009mg) had equivalent mirogabalin AUC; BM2216 showed good sustained\u2010release properties.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n BM2216 SR was safe and shows linear PK (5.5\u20133\u2009mg single dose). Due to significant food effect and comparable QD exposure to the reference drug, postprandial QD administration is recommended. These data support further efficacy trials in neuropathic pain patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.71284","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:42Z","timestamp":1788307242000},"page":"10795-10813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First\u2010In\u2010Human Study of Mirogabalin (\n BM2216<\/scp>\n ) Sustained\u2010Release Tablets: Safety, Tolerability, Pharmacokinetics, Food Effect and Dose Proportionality With Comparison to Mirogabalin Besylate in Healthy Participants"],"prefix":"10.1111","volume":"28","author":[{"given":"Peiyang","family":"Song","sequence":"first","affiliation":[{"name":"Phase I Clinical Trial Center Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing Chongqing 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