Safety, Tolerability, Pharmacokinetics and Activity of GS-9450 in Adults With Non-Alcoholic Steatohepatitis (NASH)
A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Activity of GS 9450 in Adults With Non-Alcoholic Steatohepatitis (NASH)
1 other identifier
interventional
124
2 countries
33
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2008
Shorter than P25 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2008
CompletedFirst Submitted
Initial submission to the registry
August 21, 2008
CompletedFirst Posted
Study publicly available on registry
August 25, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2009
CompletedFebruary 4, 2014
January 1, 2014
1 year
August 21, 2008
January 3, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Baseline to Post-treatment Week 24
Secondary Outcomes (2)
Pharmacokinetics of GS-9450 and its metabolites
Weeks 2 and 4
Change from baseline in alanine aminotransferase (ALT)
Baseline to Week 4
Study Arms (5)
Cohort 1
EXPERIMENTAL22 subjects to receive 1 mg GS-9450 for 4 weeks
Cohort 2
EXPERIMENTAL22 subjects to receive 5 mg GS-9450 for 4 weeks
Cohort 3
EXPERIMENTAL22 subjects to receive 10 mg GS-9450 for 4 weeks
Cohort 4
EXPERIMENTAL22 subjects to receive 40 mg GS-9450 for 4 weeks
Cohort 5
PLACEBO COMPARATOR22 subjects to receive placebo to match GS-9450 for 4 weeks
Interventions
GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (33)
Unknown Facility
Tucson, Arizona, United States
Unknown Facility
Fresno, California, United States
Unknown Facility
Fullerton, California, United States
Unknown Facility
San Diego, California, 92161, United States
Unknown Facility
San Mateo, California, United States
Unknown Facility
Lakewood, Colorado, United States
Unknown Facility
Washington D.C., District of Columbia, United States
Unknown Facility
Jacksonville, Florida, United States
Unknown Facility
Atlanta, Georgia, 30309, United States
Unknown Facility
Marietta, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Des Moines, Iowa, United States
Unknown Facility
Kansas City, Kansas, 66160, United States
Unknown Facility
Monroe, Louisiana, United States
Unknown Facility
New Orleans, Louisiana, United States
Unknown Facility
Ann Arbor, Michigan, 48109, United States
Unknown Facility
Troy, Michigan, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Plainview, New York, United States
Unknown Facility
Syracuse, New York, United States
Unknown Facility
Asheville, North Carolina, United States
Unknown Facility
Durham, North Carolina, United States
Unknown Facility
Raleigh, North Carolina, United States
Unknown Facility
Clevleand, Ohio, United States
Unknown Facility
Providence, Rhode Island, 02905, United States
Unknown Facility
Dallas, Texas, 75203, United States
Unknown Facility
Galveston, Texas, 77555, United States
Unknown Facility
Irving, Texas, United States
Unknown Facility
Charlottesville, Virginia, United States
Unknown Facility
Falls Church, Virginia, United States
Unknown Facility
Richmond, Virginia, United States
Unknown Facility
Paris, 75020, France
Unknown Facility
Vandœuvre-lès-Nancy, 54511, France
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Elsa Mondou, MD
Gilead Sciences
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2008
First Posted
August 25, 2008
Study Start
August 1, 2008
Primary Completion
August 1, 2009
Study Completion
September 1, 2009
Last Updated
February 4, 2014
Record last verified: 2014-01