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

Study Overview
=================
Brief Summary
-----------------
To determine safety and effectiveness of low-dose therapeutic AEGR-733 +/- atorvastatin, ezetimibe or fenofibrate (compared to placebo) on liver fat accumulation measured by Magnetic Resonance Spectroscopy

Detailed Description
-----------------
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.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate Low Doses of the MTP-Inhibitor AEGR-733 on Hepatic Fat Accumulation as Measured by Magnetic Resonance Spectroscopy

Conditions
-----------------
Hyperlipidemia

Intervention / Treatment
-----------------
* Drug: AEGR-733
* Drug: placebo
* Drug: AEGR-733
* Drug: AEGR-733
* Drug: AEGR-733
* Drug: AEGR-733 and atorvastatin
* Drug: AEGR-733 and fenofibrate
* Drug: AEGR-733 and ezetimibe


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: placebo<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 2<br>2.5 mg AEGR-733 | Drug: AEGR-733<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 3<br>5 mg AEGR-733 | Drug: AEGR-733<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 4<br>7.5 mg AEGR-733 | Drug: AEGR-733<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 5<br>10 mg AEGR-733 | Drug: AEGR-733<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 6<br>5 mg AEGR-733 + 20 mg atorvastatin | Drug: AEGR-733 and atorvastatin<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 7<br>5 mg AEGR-733 + 145 mg fenofibrate | Drug: AEGR-733 and fenofibrate<br>* 3 capsules each evening for each 4-week period<br>|
| Active Comparator: 8<br>5 mg AEGR-733 + 10 mg ezetimibe | Drug: AEGR-733 and ezetimibe<br>* 3 capsules each evening for each 4-week period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Percent Hepatic Fat | Absolute change from Baseline in percent hepatic fat | Baseline and 12 weeks on study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Percent Hepatic Fat | Absolute change from Baseline in percent hepatic fat | Baseline and 12 weeks on study drug | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LDL, hepatic fat