Safety, Tolerability, Pharmacokinetics and Activity of GS-9450 in Adults With Non-Alcoholic Steatohepatitis (NASH)

Inclusion Criteria: * 18-75 years of age * ALT \> 60 U/L * fatty liver on screening ultrasound * and biopsy-confirmed NASH * platelet count \>/= 75,000/mm3 and adequate hematologic function (absolute neutrophil count \>/= 1,500/mm3, hemoglobin \>/= 11.0 g/dL) * calculated creatinine clearance \>/= 70 mL/min * non-insulin dependent diabetes for \< 10 years is allowed if stably managed for at least 6 months prior to screening * stable weight (no weight loss \> 4%) for 8 weeks prior to screening and should maintain consistent diet, food intake, and physical exercise during the study * must have been on stable therapy for at least 3 months prior to screening if receiving 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors, niacin, fibrates, vitamin E or angiotensin receptor blockers * must have been on a stable treatment regimen for at least 3 months prior to screening if receiving other drugs possibly associated with hepatic adverse events (e.g., isoniazid, itraconazole, ketoconazole, rifabutin, rifampin, and other agents with significant hepatotoxic potential) Exclusion Criteria: * Insulin dependent diabetes mellitus, treatment with sulfonylureas (may be allowed pending results from a drug-drug interaction study), subjects receiving glitazones at screening or within 6 months of screening, presence of diabetic peripheral neuropathy or gastroparesis * A \> 4% decrease in weight within 8 weeks of screening * cirrhosis or decompensated liver disease (defined as conjugated bilirubin \> 1.5 x the upper limit of the normal range (ULN), prothrombin time \> 1.5 x ULN, serum albumin \< 3.0 g/dL, or prior history of clinical hepatic decompensation * presence of other form of liver disease other than NASH * history of excess alcohol ingestion, averaging \> 3 drinks/day in the previous 2 years; or current alcohol intake averaging \> 2 drinks/day for females and \> 3 drinks per day for males; history of or current binge drinking * serological evidence of co-infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV * evidence of hepatocellular carcinoma (i.e., α-fetoprotein \> 50 ng/mL) * history of ingesting drugs possibly associated with hepatic steatosis within the past year * history of total parenteral nutrition within the past 6 months * prior history of gastroplasty, jejunoileal, or jejunocolonic bypass surgery * history of ingesting drugs within the past 3 months that may improve NASH and associated fibrosis * significant gastrointestinal disease that would interfere with absorption of oral medications; inflammatory bowel disease * major surgery within the past year * clinically significant abnormalities on ECG or other ECG findings that the investigator considers a safety risk * significant systemic or major illnesses other than liver disease that, in the opinion of the investigator, would preclude treatment and adequate follow up * prior or current malignancy involving any organ system and skin cancer (previously excised basal cell carcinoma allowed) * acute ongoing infection, or symptoms of infection * pregnant or breastfeeding females * acute substance abuse within the past year. * history of ingesting anti-TNFα drugs or immunomodulators within the past 3 months