This study is the first study of losmapimod in Japanese subjects. This study will be a
single-center, single blind, phase I and two part study to characterize the safety,
tolerability, pharmacokinetic and pharmacodynamic profiles in healthy Japanese volunteers
(male and female of non-childbearing potential). Part1 will be a single dose, randomized,
three-period, placebo-controlled and dose escalation part. Each subject will participate in 3
dosing sessions, and receive, on separate days, three of four treatments of losmapimod 2.5,
7.5 and 20 mg, and the matching placebo in the fasted state after overnight fast (at least 10
hours). The design incorporates sufficient washout between treatments (at least 7 days after
the previous administration), and is an efficient design for the study objectives. Part 2
will be a fixed dose and placebo-controlled part. Each subject will participate in one dosing
session, and receive losmapimod 7.5 mg or the matching placebo twice daily in the fasted
state for 14 days. Only subjects will be blind to the sequence and dose studied. The study
will include the placebo treatment to allow a valid evaluation of adverse events attributable
to treatment versus those independent of treatment. Approximately 18 subjects in each part
will receive treatments of losmapimod and/or placebo in the design. The primary objective of
the study is to characterize the safety and tolerability of single doses and repeat doses of
losmapimod in healthy Japanese subjects. Serial pharmacokinetic samples will be collected and
safety assessments will be performed following each dose.