Chaoying Hu1, Yijun Wang1, Rong Song1, Chen Yu1, Xiaoyan Luo2, Jingying Jia3. 1. Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai Rd.(M), Shanghai, 200031, China. 2. Sumitomo Pharmaceuticals (Suzhou) Co. Ltd., Beijing, China. 3. Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai Rd.(M), Shanghai, 200031, China. jyjia@shxh-centerlab.com.
Abstract
BACKGROUND AND OBJECTIVE: The pharmacokinetics of lurasidone have been studied in healthy Japanese and Caucasian subjects, but not in Chinese subjects. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of oral lurasidone in healthy Chinese subjects. METHODS: This single-center, randomized, parallel-group, placebo-controlled, and double-blind study evaluated the pharmacokinetics, safety, and tolerability of oral lurasidone administered as a single dose (20, 40, and 80 mg) and multiple doses for 5 days (40 mg administered once daily) in healthy Chinese subjects. Serum lurasidone and its metabolites were quantified using high-performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters for lurasidone and its metabolites were calculated using non-compartmental analysis of WinNonlin® version 6.2. Safety analyses were recorded using physical examinations, vital signs, electrocardiogram, and clinical laboratory tests. RESULTS:Serum concentrations of lurasidone reached maximum concentration (C max) within 1.0-3.0 h after each single dose, and then decreased biphasically, with a mean half-life (t ½) from 18.1 to 25.5 h over the dose range of 20-80 mg. The area under the concentration-time curve (AUC) and C max values increased approximately dose proportionally. Lurasidone steady state was achieved after 5 days of daily dosing and the accumulation index of the AUC during a dosage interval (AUCτ) was 1.25, smaller than theoretical cumulative coefficient (1.76). Similar results were observed for the metabolites (ID-14283, ID-14326, and ID-11614). No severe adverse events (AEs) were observed in the single- or multiple-dose studies and no subject discontinued from the study due to AEs. The most common reported AEs were somnolence, increased blood prolactin, and restlessness, with a higher rate as dose increased. CONCLUSION:Lurasidone was safe and well-tolerated in healthy Chinese subjects, following single doses in the range of 20 to 80 mg and multiple doses of 40 mg/day for 5 days. Linear increase in lurasidone C max and AUC values were seen following single doses from 20 to 80 mg. There was no unexpected accumulation after multiple administrations of lurasidone at 40 mg/day, and the pharmacokinetic characteristics were consistent with the conclusion obtained in the previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifiers NCT02174510 and NCT02174523.
RCT Entities:
BACKGROUND AND OBJECTIVE: The pharmacokinetics of lurasidone have been studied in healthy Japanese and Caucasian subjects, but not in Chinese subjects. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of oral lurasidone in healthy Chinese subjects. METHODS: This single-center, randomized, parallel-group, placebo-controlled, and double-blind study evaluated the pharmacokinetics, safety, and tolerability of oral lurasidone administered as a single dose (20, 40, and 80 mg) and multiple doses for 5 days (40 mg administered once daily) in healthy Chinese subjects. Serum lurasidone and its metabolites were quantified using high-performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters for lurasidone and its metabolites were calculated using non-compartmental analysis of WinNonlin® version 6.2. Safety analyses were recorded using physical examinations, vital signs, electrocardiogram, and clinical laboratory tests. RESULTS: Serum concentrations of lurasidone reached maximum concentration (C max) within 1.0-3.0 h after each single dose, and then decreased biphasically, with a mean half-life (t ½) from 18.1 to 25.5 h over the dose range of 20-80 mg. The area under the concentration-time curve (AUC) and C max values increased approximately dose proportionally. Lurasidone steady state was achieved after 5 days of daily dosing and the accumulation index of the AUC during a dosage interval (AUCτ) was 1.25, smaller than theoretical cumulative coefficient (1.76). Similar results were observed for the metabolites (ID-14283, ID-14326, and ID-11614). No severe adverse events (AEs) were observed in the single- or multiple-dose studies and no subject discontinued from the study due to AEs. The most common reported AEs were somnolence, increased blood prolactin, and restlessness, with a higher rate as dose increased. CONCLUSION:Lurasidone was safe and well-tolerated in healthy Chinese subjects, following single doses in the range of 20 to 80 mg and multiple doses of 40 mg/day for 5 days. Linear increase in lurasidone C max and AUC values were seen following single doses from 20 to 80 mg. There was no unexpected accumulation after multiple administrations of lurasidone at 40 mg/day, and the pharmacokinetic characteristics were consistent with the conclusion obtained in the previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifiers NCT02174510 and NCT02174523.
Authors: Jeffrey A Lieberman; T Scott Stroup; Joseph P McEvoy; Marvin S Swartz; Robert A Rosenheck; Diana O Perkins; Richard S E Keefe; Sonia M Davis; Clarence E Davis; Barry D Lebowitz; Joanne Severe; John K Hsiao Journal: N Engl J Med Date: 2005-09-19 Impact factor: 91.245