MIT-001 is a novel ferroptosis inhibitor that is a potent mitochondrial-targeting antioxidant targeting various inflammatory diseases. Utilizing pharmacokinetic (PK) and safety data from previous clinical trials in healthy individuals with preclinical efficacy data from the animal disease models, we aimed to develop a population PK model for MIT-001 to provide evidence for selecting optimal dosage in clinical trials with oral mucositis (OM) patients. The PK model was developed using data from three phase 1 clinical trials with NONMEM software. Covariate analysis included demographic characteristics and clinical laboratory tests. Models were validated using objective function value, goodness of fit plots, bootstrap analysis, and prediction-corrected visual predictive check. PK profiles of MIT-001 across various doses were simulated using the final population PK model. A three-compartment model with linear elimination and first-order absorption without a lag time best described the PK profile of MIT-001. Weight and ALT were significant covariates for the peripheral compartment and clearance, respectively. The simulated PK profile showed that 97.4% of patients are expected to reach effective exposure after twice weekly 30 mg SC dose in 3 weeks. Furthermore, 93.6% of patients are expected to be within a tolerable range after 13 weeks of 80 mg SC dosing. A 30 to 80 mg twice weekly SC dose is expected to be both effective and tolerable for OM patients.
Bae et al. (Wed,) studied this question.