Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule.

Abstract

Vatiquinone, a 15-lipoxygenase (LO) inhibitor, is an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulation of energy metabolism. This investigation discusses the results of the food effect and three times a day (TID) dosing schedule studies data. The food effect study showed that absorption is significantly enhanced when vatiquinone was administered with fatty meals, either solid or liquid. Mean vatiquinone area under the concentration-time curve (AUC) values were 22-fold and 3-fold higher in subjects who consumed fatty meals and liquid meals, respectively, compared with subjects who fasted. With fatty meals, the intersubject variabilities appeared lower for AUC. The TID dosing study showed that the typical individual pharmacokinetic concentration profile exhibited 3 peaks on both Day 1 and after multiple dosing on Day 6. Vatiquinone exposures, AUC, and maximum concentration (C_max) appeared to increase from 200 to 400 mg in a dose-proportional manner with moderate variabilities, ranging from approximately 35% to 65%. The mean Day 6 accumulation ratio (AR_AUC) suggested an accumulation ratio of 1.61 and 1.73 for 200 and 400 mg, respectively. The results of both studies support the recommendation of administering vatiquinone TID with fatty meals taken on a convenient dosing regimen.