405 SERUM LEVELS OF CHEMERIN, VASPIN, VISFATIN AND SPECAM-1 IN PATIENTS WITH CHRONIC HEPATITIS C

Abstract

injury in hepatitis C and non-alcoholic steatohepatitis patients. The safety, tolerability, and pharmacokinetics (PK) of single and multiple oral dose administration of GS-9450 in healthy volunteers were studied. Gender and food effects were also evaluated. Methods: Two Phase I, randomized, double-blind, placebo-controlled studies were conducted to evaluate the PK of GS-9450 following single and multiple dose administration. Single ascending oral doses of 0, 5, 10, 20, 40, 80 and 120mg of GS-9450 were administered to 48 healthy male volunteers. Volunteers in the 40mg cohort who received the single dose in a fasted state also received GS-9450 after a high fat breakfast. Six female volunteers received GS-9450, 40mg, to evaluate the effect of gender on GS-9450 PK. In the second study, 24 volunteers received multiple daily doses of 0, 40, 80 and 120mg of GS-9450 over 15 days. Results: GS-9450 reached peak plasma concentrations (Cmax) at 0.5−3 hours (hrs) post-dose. GS-9450 was eliminated with median elimination half-lives (T1/2) of approximately 10 to 16 hrs across all dose levels. Systemic exposure to GS-9450 increased in a dose-proportional manner over the range of single and multiple doses. Only 2−4% of the dose was excreted unchanged as GS-9450 in urine consistent with metabolism of GS-9450 in the liver. Neither food nor gender had a significant effect on the PK of GS-9450. GS-9450 was well tolerated without serious or severe adverse events (AEs). The most frequently reported AE was headache. There was no clear relationship between dose and incidence, frequency, onset or duration of treatment-related AEs, which were transient and mild in nature. One male volunteer discontinued dosing due to development of a rash of mild severity. No clinically significant changes in laboratory data, vital signs, and ECG values were observed. Conclusions: The half-life of GS-9450 supports once-daily dosing and no evidence was found for a significant gender or food effect on GS-9450 PK. GS-9450 was well tolerated by healthy male and female volunteers.