Overview

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