Safety, Tolerability, and Pharmacokinetics of the Novel Adenosine A2A Antagonist/Inverse Agonist KW-6356 Following Single and Multiple Oral Administration in Healthy Volunteers.

Abstract

KW-6356 is an adenosine A2A receptor-selective antagonist and inverse agonist. We conducted 2 studies: study 6356-001 (no NCT number), a randomized, double-blind, placebo-controlled phase 1 trial of single ascending (1, 3, 10mg) and multiple (6mg once daily) oral doses of KW-6356 in healthy Japanese subjects; and study 6356-004 (NCT03830528), including a randomized, double-blind, placebo-controlled phase 1 trial of single ascending (21, 42, 60mg) and multiple (24mg once daily) oral doses of KW-6356, and a phase 1 open-label trial of multiple oral doses (6mg once daily) of KW-6356 in healthy Japanese and White subjects, to evaluate the safety, tolerability, and pharmacokinetics of KW-6356. KW-6356 was well tolerated after administration of single doses of up to 60mg and multiple doses of up to 24mg once daily for 14days. The pharmacokinetics of KW-6356 were linear after a single dose of up to 60mg KW-6356. The mean terminal elimination half-life of KW-6356 ranged from 18.4 to 43.1hours following administration of single doses of 1-60mg. There was no clear difference in the safety or pharmacokinetics of KW-6356 between healthy Japanese and White subjects.