First-In-Human Study of Mirogabalin (BM2216) Sustained-Release Tablets: Safety, Tolerability, Pharmacokinetics, Food Effect and Dose Proportionality With Comparison to Mirogabalin Besylate in Healthy Participants

Aim: To characterise the pharmacokinetics (PKs) and safety of BM2216 sustained-release (SR) tablets after single-dose oral administration under fasted/fed conditions in healthy participants, assess the effect of food and dose proportionality, and compare the single and multiple-dose PK of BM2216 SR tablets with mirogabalin besylate tablets to estimate the bioavailability. Materials and Methods: This was a single-centre, randomised, open-label, phase I study conducted in healthy adult participants aged 18–45 years old, consisting of three parts: Part 1 (Food effect and single-dose PK comparison): 18 participants were 1:1:1 randomised into three sequences: (1) 16.5 mg BM2216 (fasting 18:00, QD); (2) 15 mg mirogabalin besylate tablets (fasting 18:00/next-day 6:00, 7.5 mg/dose); (3) 16.5 mg BM2216 (post-high-fat dinner, QD). A 3-period crossover design with a 72 h washout period; Part 2 (Single-dose proportionality): 32 participants were equally assigned to four groups, receiving BM2216 SR tablets (5.5, 11, 16.5, or 33 mg) 30 min post-standard meal, respectively; Part 3 (Multiple-dose PK comparison): 16 participants were 1:1 randomised into two sequences: (1) BM2216 (post-dinner, 16.5 mg QD, four consecutive days); (2) 15 mg mirogabalin besylate tablets (fasting 18:00/next-day 6:00, 7.5 mg/dose, four consecutive days). Crossover was conducted with a 72 h washout period. PK parameters were calculated and compared using non-compartmental analysis. Results: 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 mg dose groups, while vertigo was only seen in the 33 mg group, no serious AEs occurred. Single postprandial doses (5.5–33 mg) exhibited linear PKs: T max median 3.00–5.02 h, with dose-proportional increases in C max, AUC0−t and AUC0−∞. Multiple doses (16.5 mg QD, 4 days) had T max,ss median 5.996 h, t 1/2,ss mean 3.8075 h; The RAC,Cmax and RAC,AUC were 0.9965 and 1.0150, indicating no accumulation; high-fat meal significantly extending T 1/2 by 3.5 h, increasing C max by 16%, delaying T max by 3 h and raising AUC by 30%. Postprandial BM2216 (16.5 mg) and fasting mirogabalin besylate (15 mg) had equivalent mirogabalin AUC; BM2216 showed good sustained-release properties. Conclusions: BM2216 SR was safe and shows linear PK (5.5–3 mg 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. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.