Pharmacokinetic and Safety Profiles of MIT-001, a Novel Ferroptosis Inhibitor, After Subcutaneous Administration in Healthy Participants.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.