Lee Sujong, Bae Sungyeun, Yu Kyung-Sang, Lee SeungHwan
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Drug Des Devel Ther. 2025 Sep 9;19:7999-8008. doi: 10.2147/DDDT.S541415. eCollection 2025.
MIT-001 is a novel ferroptosis inhibitor with therapeutic potential for oxidative stress-related diseases. This study aimed to evaluate the pharmacokinetic (PK) and safety profiles of MIT-001 after subcutaneous (SC) administration in healthy participants.
A randomized, double-blind, placebo-controlled, dose-escalation study was conducted in two parts: single ascending dose (SAD) and multiple ascending dose (MAD) studies. In the SAD study, participants received a single SC dose of MIT-001 at 10, 20, or 40 mg, with the 40 mg cohort also receiving a single IV dose in a crossover manner. In the MAD study, participants received SC doses of 20 or 40 mg once daily for seven consecutive days. Safety and tolerability were assessed by monitoring adverse events (AEs), physical examinations, vital signs, and clinical laboratory tests.
A total of 40 participants completed the study, with 24 in the SAD study and 16 in the MAD study. MIT-001 was rapidly absorbed, reaching the maximum concentration at a median time of 1.5-2.5 h. Accumulation ratios after multiple SC administrations were 2.75-2.77. PK profiles were comparable between SC and IV formulations. The most common AEs were mild local reactions at the injection site, with no statistically significant differences in incidence across dose levels. No serious AEs were reported.
The systemic exposure of MIT-001 after SC administration increased linearly across the dose levels of 10-40 mg. MIT-001 was well tolerated after a single SC dose of 10-40 mg and multiple SC doses of 20-40 mg in healthy participants.
MIT - 001是一种新型铁死亡抑制剂，对氧化应激相关疾病具有治疗潜力。本研究旨在评估健康受试者皮下注射（SC）MIT - 001后的药代动力学（PK）和安全性。
进行了一项随机、双盲、安慰剂对照、剂量递增研究，分为两个部分：单剂量递增（SAD）和多剂量递增（MAD）研究。在SAD研究中，受试者接受10、20或40 mg的单次皮下MIT - 001剂量，40 mg队列还以交叉方式接受单次静脉注射剂量。在MAD研究中，受试者连续7天每天接受20或40 mg的皮下剂量。通过监测不良事件（AE）、体格检查、生命体征和临床实验室检查来评估安全性和耐受性。
共有40名受试者完成研究，其中24名在SAD研究中，16名在MAD研究中。MIT - 001吸收迅速，在中位时间1.5 - 2.5小时达到最大浓度。多次皮下给药后的蓄积比为2.75 - 2.77。皮下和静脉制剂的PK曲线具有可比性。最常见的AE是注射部位的轻度局部反应，各剂量水平的发生率无统计学显著差异。未报告严重AE。
皮下注射MIT - 001后的全身暴露在10 - 40 mg剂量水平上呈线性增加。在健康受试者中，单次皮下注射10 - 40 mg和多次皮下注射20 - 40 mg后，MIT - 001耐受性良好。
