Journal Article

Pharmacokinetics, Pharmacodynamics, and Safety of Peficitinib (ASP015K) in Healthy Male Caucasian and Japanese Subjects

Nishimura, Tetsuya, Shibata, Mai, Saito, Masako, Toyoshima, Junko, Oda, Kazuo, Hatta, Toshifumi, Kaneko, Yuichiro

2020

Overview

Background and Objective Peficitinib pharmacokinetics and pharmacodynamics have been characterized mainly in Caucasian subjects. This study investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of peficitinib in healthy Japanese subjects compared with Caucasian subjects. Methods In this single-center, randomized, double-blind, placebo-controlled study, a cohort of healthy Japanese ( n  = 24) and Caucasian ( n  = 24) men received a single oral dose of peficitinib (20, 60, or 200 mg) or placebo. Another cohort of Japanese men ( n  = 24) received peficitinib (10, 30, or 100 mg) or placebo twice daily for 7 days. Pharmacokinetic and pharmacodynamic parameters were assessed, and adverse events (AEs) monitored throughout. Results Dose proportionality of maximum plasma drug concentration ( C max ) and area under the plasma concentration–time curve extrapolated to infinity (AUC inf ) was demonstrated for both ethnicities. The geometric mean ratio for dose-normalized C max was 45.7–98.8% higher and AUC inf was 33.8–66.4% higher in Japanese versus Caucasian subjects. Mean peak inhibition of STAT5 phosphorylation was higher in Japanese than Caucasian subjects for a given peficitinib dose, but inhibition was comparable across ethnicities for a given plasma peficitinib concentration. In the multiple-dose study, plasma peficitinib concentrations were similar on day 1 and day 7. All AEs were mild, and none resulted in study discontinuation. Conclusions Peficitinib was well tolerated at doses up to 200 mg daily for 7 days in healthy Japanese subjects. Dose-proportional exposure was demonstrated across the single-dose range of 20–200 mg, with greater peficitinib exposure in Japanese compared with Caucasian subjects. The pharmacokinetic/pharmacodynamic relationships were considered comparable between these populations. ClinicalTrials.gov identifier NCT01225224.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Drug dosages / Ethnicity / Internal Medicine / Laboratories / Medicine / Medicine & Public Health / NCT / NCT01225224 / Original / Original Research Article / Pharmacodynamics / Pharmacokinetics / Pharmacology/Toxicology / Pharmacotherapy / Plasma / Studies / TNF inhibitors / Tumor necrosis factor-TNF / Urine