Pharmacokinetics and safety of a new generic lurasidone: a phase I bioequivalence study in healthy Chinese subjects

Zhengzhi Liu; Jinling Xue; Qiaohuan Deng; Yanli Wang; Lixiu Zhang; Lang Liu; Nan Xiao; Tianying Chang; Yingzi Cui; Yang Cheng; Guangwen Liu; Wanhua Wang; Yannan Zhou; Wei Yang; Xinyao Qu; Jiahui Chen; Yicheng Zhao; Zeyu Wang; Haimiao Yang

doi:10.1007/s00210-024-03055-1

Pharmacokinetics and safety of a new generic lurasidone: a phase I bioequivalence study in healthy Chinese subjects

Naunyn Schmiedebergs Arch Pharmacol. 2024 Apr 21. doi: 10.1007/s00210-024-03055-1. Online ahead of print.

Authors

Zhengzhi Liu^#¹, Jinling Xue^#², Qiaohuan Deng¹, Yanli Wang¹, Lixiu Zhang³, Lang Liu⁴, Nan Xiao², Tianying Chang¹, Yingzi Cui¹, Yang Cheng¹, Guangwen Liu¹, Wanhua Wang¹, Yannan Zhou¹, Wei Yang¹, Xinyao Qu¹, Jiahui Chen¹, Yicheng Zhao⁵, Zeyu Wang⁶, Haimiao Yang⁷

Affiliations

¹ Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
² Clinical Research Center, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
³ Lung Disease Center, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
⁴ The Clinical Trial Quality Control Center, Ansiterui Medical Technology Consulting Co., Ltd., Changchun, China.
⁵ Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
⁶ Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China. zeyu781022@163.com.
⁷ Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China. haimiaoyang@outlook.com.

^# Contributed equally.

PMID: 38643450
DOI: 10.1007/s00210-024-03055-1

Abstract

Latuda^® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda^® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda^®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda^®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda^® were as follows: the C_max was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC_0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC_0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, C_max, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC_0-t, AUC_0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both C_max and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda^® were as follows: the C_max was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC_0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC_0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (C_max, AUC_0-t, AUC_0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda^® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda^® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).

Keywords: Antipsychotic; Bioequivalence; Lurasidone; Pharmacokinetics; Tolerability.