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

Purpose

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).

Condition	Intervention	Phase
Nonalcoholic Steatohepatitis	Drug: GS-9450 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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)

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Safety and Tolerability [ Time Frame: Throughout 8 weeks (4 weeks on treatment and 4 weeks post-treatment) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Plasma pharmacokinetic parameters of GS-9450 and metabolites [ Time Frame: From Week 1 on treatment through 1st week off-treatment ] [ Designated as safety issue: No ]
Change from baseline in ALT levels at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Enrollment:	124
Study Start Date:	August 2008
Study Completion Date:	September 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 22 subjects to receive 1 mg GS-9450	Drug: GS-9450 GS-9450 1 mg by mouth once daily for 4 weeks
Experimental: 2 22 subjects to receive 5 mg GS-9450	Drug: GS-9450 5 mg GS-9450 by mouth once daily for 4 weeks
Experimental: 3 22 subjects to receive 10 mg GS-9450	Drug: GS-9450 GS-9450 10 mg by mouth once daily for 4 weeks
Experimental: 4 22 subjects to receive 40 mg GS-9450	Drug: GS-9450 GS-9450 40 mg by mouth once daily for 4 weeks
Placebo Comparator: 5 22 subjects to receive Placebo	Drug: Placebo Placebo capsules that mimic the physical appearance of GS-9450 1, 5, 10, and 40 mg capsules taken by mouth once daily for 4 weeks

Detailed Description:

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).

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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 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 HBV, 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00740610

Show 33 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Elsa Mondou, MD

Gilead Sciences

More Information

No publications provided

Responsible Party:	Elsa Mondou, MD, Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00740610 History of Changes
Other Study ID Numbers:	GS-US-228-0101
Study First Received:	August 21, 2008
Last Updated:	August 20, 2010
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 16, 2013