The Effect of Food on the Pharmacokinetics and Gastrointestinal Tolerability of Bersiporocin, a Novel Oral Prolyl-tRNA-Synthetase Inhibitor

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Purpose: Bersiporocin is a first-in-class prolyl-tRNA-synthetase inhibitor under clinical development for the treatment of idiopathic pulmonary fibrosis. In a prior first-in-human study, the incidence of gastrointestinal (GI) adverse events (AEs) differed across prandial conditions. This study aimed to evaluate the effect of food on the pharmacokinetics (PKs) and safety profile of bersiporocin. Patients and Methods: This randomized, open-label, single-dose, three-period crossover study enrolled 36 healthy Korean participants. Each participant received a single oral dose of bersiporocin 200 mg under three conditions: fasted (A), 30 minutes after a high-fat meal (B), and 2 hours after a high-fat meal (C), with a 7-day washout between periods. Plasma concentrations of bersiporocin and its active metabolite M8 were quantified using a validated LC-MS/MS assay, and PK parameters were determined by non-compartmental analysis. Safety was evaluated by monitoring AEs, clinical laboratory tests, vital signs, and electrocardiograms. Results: , was comparable across conditions, with geometric mean ratios (90% confidence intervals) of 0.9380 (0.8500-1.0351) and 0.9944 (0.9000-1.0988) for B and C relative to A, respectively. Similar PK trends were observed for M8. A higher incidence of GI AEs was observed in condition B (45.7%) than in conditions A (25.7%) or C (24.2%). Systemic exposure did not differ between participants with and without vomiting. Conclusion: A high-fat meal delayed the oral absorption rate of bersiporocin but did not have a clinically significant effect on systemic exposure to bersiporocin or M8. Given the increased incidence of GI AEs under early postprandial conditions, administration under fasted conditions or at least 2 hours postprandially may be appropriate for future clinical studies.

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