Evaluate Low Doses of AEGR-733 on Hepatic Fat Accumulation by MRS

The goal within the current development program and this study is to investigate whether lower doses of AEGR-733 can result in significant reductions in LDL-C and TGs while providing fewer gastrointestinal adverse events and less hepatic fat accumulation than seen in studies with higher doses. The potential for atorvastatin, ezetimibe or the PPAR-alpha agonist (fenofibrate) to ameliorate any hepatic fat accumulation will also be investigated. The twelve week dosing schedule allows us to demonstrate the longer term effects of lower doses of MTP-I on hepatic fat accumulation.

Inclusion criteria

• LDL-C between 100 and 190 mg/dL
• Hepatic fat under 6.2% per MRS

Exclusion criteria

• Pregnant or lactating females
• Uncontrolled hypertension >180/95 mmHg
• Chronic renal insufficiency - serum creatinine >2.5 mg/dL at screen
• Liver disease; i.e., hepatitis, cirrhosis
• Major surgery within 3 months of screen
• Cardiac insufficiency
• Hx of malignancy other than basal or squamous cell within past 5 yrs
• Participation in any investigational drug study within 6 wks of screen
• Prior exposure to AEGR-733 in past 12 months
• Serious or unstable medical or psychological conditions
• More than one alcoholic drink per day
• Regular consumption of grapefruit juice or meds known to be metabolized by CYP 3A4
• Currently taking corticosteroids
• Other lipid-lowering meds (washout permitted)
• Fish oil, niacin grater than 200 mg/day and herbal weight loss products (washout permitted)
• Acute CVD or event within previous 6 months
• Diabetes Mellitus
• Hepatitis B or C
• Medicated COPD
• Idiopathic pulmonary fibrosis
• G.I. disorders that cause chronic diarrhea
• Fasting triglycerides =/> 400 mg/dL
• Body Mass Index > 35kg/m2