Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers

Mitiperstat (AZD4831) is a novel irreversible oral myeloperoxidase inhibitor in clinical development for heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis and chronic obstructive pulmonary disease. This study evaluated the pharmacokinetics, safety and tolerability of multiple ascending doses of mitiperstat in healthy male Japanese and Chinese volunteers.

Three cohorts of eight Japanese participants were randomized to receive once-daily oral doses of mitiperstat 2.5, 5 or 10 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo, per cohort). One cohort of eight Chinese participants was randomized to receive mitiperstat 5 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo).

Mitiperstat was rapidly absorbed, with a time to maximum plasma concentration of 1–2 h. Exposure was dose proportional over the investigated dose range, as assessed by area under the concentration–time curve and maximum and trough plasma concentrations. Steady state was reached within 10 days, and accumulation was observed, consistent with the observed long elimination half-life of mitiperstat (50.2–57.8 h). Except for a few events of maculopapular rash, mitiperstat up to 5 mg was well tolerated in participants of Japanese or Chinese origin.

The pharmacokinetics of mitiperstat were similar among Japanese and Chinese participants. These characteristics were similar to those in a previous multiple ascending-dose study in healthy primarily white and Black/African American volunteers. Therefore, the pharmacokinetics of mitiperstat do not affect dosing regimens in these different populations.

NCT04232345 (03/01/2020).