Bioequivalence and Tolerability of 2 Lurasidone Formulations: A Randomized, Single-Dose, 2-Period, Crossover Study in Healthy Chinese Subjects Under Fasting and Fed Conditions

Abstract

Lurasidone is utilized in the treatment of schizophrenia and bipolar depression in adults and adolescents. In this work, a randomized, single-dose, 2-period crossover study was designed and conducted to evaluate the bioequivalence and safety of 2 lurasidone tablets. A total of 111 healthy Chinese subjects received a single dose of 40 mg lurasidone test (T) or reference (R) tablets under fasting or fed conditions, with a 7-day washout period. Blood samples were collected and lurasidone plasma concentration was quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic properties were determined by a non-compartmental analysis, and C_max, AUC_0-t, and AUC_0-inf were used for bioequivalence evaluation. As a result, the 90% confidence intervals of the geometric mean ratios between T and R fell within 80%-125% whether under fasting or fed conditions, indicating that the 2 lurasidone formulations were bioequivalent. Meanwhile, the C_max and AUC of both T and R were approximately 2-3 times higher in the fed state compared to the fasting state. In addition, all adverse events (AEs) were classified into grade 1, and no serious or new AEs were reported. Additionally, a shorter t_1/2 of the reference tablet was observed in this study compared to that of the other bioequivalence study conducted in older healthy Chinese subjects, which should be verified in the future.

Keywords: bioequivalence; food effect; lurasidone; pharmacokinetics; safety.