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

KW-6356 is an adenosine A 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, 10 mg) and multiple (6 mg 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, 60 mg) and multiple (24 mg once daily) oral doses of KW-6356, and a phase 1 open-label trial of multiple oral doses (6 mg 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 60 mg and multiple doses of up to 24 mg once daily for 14 days. The pharmacokinetics of KW-6356 were linear after a single dose of up to 60 mg KW-6356. The mean terminal elimination half-life of KW-6356 ranged from 18.4 to 43.1 hours following administration of single doses of 1-60 mg. There was no clear difference in the safety or pharmacokinetics of KW-6356 between healthy Japanese and White subjects.