A phase 1, randomized, double-blind, placebo-controlled, ascending dose study evaluating the safety, tolerability and pharmacokinetics of JTK-652 administered for two weeks in healthy male subjects

Infection with hepatitis-C virus (HCV)is now the most frequent cause of chronic
hepatitis, cirrhosis and hepatocellular carcinoma in most developed nations.
HCV is a blood borne pathogen that is transmitted predominantly by percutaneous
exposure. JTK-652 could be useful for treatment. JTK-652 shows an inhibitory
effect on liver cells that are hepatitis-C infected. Other than the current
protease inhibitors in development, JTK-652 is likely to have its action in the
early phase of the infection process.

Primary objectives : to investigate the safety and tolerability of multiple
oral doses of JTK-652 administered for 14 days to healthy male subjects
Secondary objectives : tot determine the pharmacokinetics of multiple oral
doses of JTK-652 administered for 14 days to healthy male subjects

Randomized, double-blind, placebo-controlled, ascending dose study in 18
healthy male subjects in two dose cohorts with nine subjects each. In each
cohort nine subjects (6 active, 3 placebo) will be randomized to receive
JTK-652 or placebo every 8 hours for 13 days with a final morning dose on Day
14.

Cohort 1 : three times daily (t.i.d.) an oral dose of 400 mg JTK-652 or placebo
on Days 1-13 with a final dose on Day 14.
Cohort 2 : t.i.d. an oral dose of 800 mg JTK-652 or placebo on Days 1-13 with a
final morning dose on Day 14

Procedures; insertion of the indwelling canula/venapuncture : some pain,
bruise, light bleeding.

JTK-652:
adverse effets in animal studies: vomiting, abnormal feaces (whitish and soft
stool, or diarrhoea ), slight increased liver enzyme and fat change in specific
liver cells, hypertrophy sinusoidal cells in liver ( not associated with
changes in bleeding ), mild increase in thyroid weight and increase in size of
typical cells in the thyroid. At very high doses sensivity for sun light was
found.