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

NCT ID: NCT00740610

Last Updated: 2014-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2009-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a Phase 2, randomized, double-blind, parallel group, placebo controlled, multicenter study investigating the safety, tolerability, pharmacokinetics and activity of multiple oral doses of GS 9450 in adults with NASH. Approximately 110 subjects 18 75 years of age with elevated ALT (\> 60 U/L at screening), fatty liver on screening ultrasound, and biopsy-proven NASH will be randomized (1:1:1:1:1) to one of five parallel treatment groups (22 subjects per treatment group) as follows:

GS-9450 1mg by mouth (PO) once daily, GS-9450 5 mg PO once daily, GS-9450 10 mg PO once daily, GS-9450 40 mg PO once daily, or Matching placebo PO once daily Qualifying subjects will be stratified by the presence/absence of type 2 diabetes (i.e., on/off oral diabetic medication at entry) and by geographic region (US and France). Following randomization, subjects will return within five business days later for a baseline visit, at which time they will be dispensed study medication and enter a 4-week treatment phase. Upon completion of the treatment phase, subjects will enter a 4 week off-treatment follow-up period. Each subject's participation in the study will last up to approximately 12 weeks (inclusive of screening, treatment phase, and off-treatment follow-up period).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Nonalcoholic Steatohepatitis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort 1

22 subjects to receive 1 mg GS-9450 for 4 weeks

Group Type EXPERIMENTAL

GS-9450

Intervention Type DRUG

GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily

Cohort 2

22 subjects to receive 5 mg GS-9450 for 4 weeks

Group Type EXPERIMENTAL

GS-9450

Intervention Type DRUG

GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily

Cohort 3

22 subjects to receive 10 mg GS-9450 for 4 weeks

Group Type EXPERIMENTAL

GS-9450

Intervention Type DRUG

GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily

Cohort 4

22 subjects to receive 40 mg GS-9450 for 4 weeks

Group Type EXPERIMENTAL

GS-9450

Intervention Type DRUG

GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily

Cohort 5

22 subjects to receive placebo to match GS-9450 for 4 weeks

Group Type PLACEBO_COMPARATOR

GS-9450 Placebo

Intervention Type DRUG

Placebo to match GS-9450 administered orally once daily

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GS-9450

GS-9450 capsules at a dose of 1, 5, 10, and 40 mg administered orally once daily

Intervention Type DRUG

GS-9450 Placebo

Placebo to match GS-9450 administered orally once daily

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Elsa Mondou, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Tucson, Arizona, United States

Site Status

Fresno, California, United States

Site Status

Fullerton, California, United States

Site Status

San Diego, California, United States

Site Status

San Mateo, California, United States

Site Status

Lakewood, Colorado, United States

Site Status

Washington D.C., District of Columbia, United States

Site Status

Jacksonville, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Marietta, Georgia, United States

Site Status

Chicago, Illinois, United States

Site Status

Des Moines, Iowa, United States

Site Status

Kansas City, Kansas, United States

Site Status

Monroe, Louisiana, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Ann Arbor, Michigan, United States

Site Status

Troy, Michigan, United States

Site Status

New York, New York, United States

Site Status

Plainview, New York, United States

Site Status

Syracuse, New York, United States

Site Status

Asheville, North Carolina, United States

Site Status

Durham, North Carolina, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Clevleand, Ohio, United States

Site Status

Providence, Rhode Island, United States

Site Status

Dallas, Texas, United States

Site Status

Galveston, Texas, United States

Site Status

Irving, Texas, United States

Site Status

Charlottesville, Virginia, United States

Site Status

Falls Church, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Paris, , France

Site Status

Vandœuvre-lès-Nancy, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States France

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GS-US-228-0101

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.