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

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The overall purpose of this study is to examine the safety, tolerability, pharmacokinetics (how the body processes a drug), and activity of GS-9450 in preventing liver damage due to scarring, or fibrosis, caused by Non-Alcoholic Steatohepatitis (also known as NASH).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences

Criteria

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