Evaluate Safety and Efficacy of AEGR-733 and Atorvastatin vs Atorvastatin Monotherapy in Hypercholesterolemia

Study Overview
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Brief Summary
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Evaluate the efficacy of combination therapy AEGR-733 plus atorvastatin 20 mg versus monotherapy on serum lipoproteins over 4 and 8 weeks of therapy. The primary efficacy parameter is percent change in LDL-C after 8 weeks of therapy.

Detailed Description
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Following a 35-day washout of current lipid-lowering medication (if any) and adherence to a low-fat diet, subjects will receive either atorvastatin 20 mg for 8 weeks, OR AEGR-733 2.5 mg + atorvastatin 20 mg for 4 weeks followed by AEGR-733 5 mg + atorvastatin 20 mg for 4 additional weeks. During the entire study, subjects will be instructed to follow a low-fat/low cholesterol diet and limit alcohol consumption to -/< 1 drink per day.

Official Title
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A Randomized, Double Blind Comparator-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of the Combination of AEGR-733 and Atorvastatin 20 mg vs Atorvastatin Monotherapy in Subjects With Moderate Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: AEGR-733


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: M/F 18-70 0-1 risk factor, mean LDL-C -/> 160 and -/< 250 mg/dL (Visit 2 & 3) 2+ risk factors, mean LDL-C -/> 130 & -/< 250 mg/dL (Visit 2 & 3) Fasting mean TGs -/< 400 mg/dL Understanding and compliance of protocol sign consent Exclusion Criteria: Females pregnant, lactating, or CBP who have not been using acceptable contraceptive methods over previous 3 months Uncontrolled hypertension >180/95 at screening Hx of chronic renal insufficiency (serum creatinine > 2.5 mg/dL) Hx of liver disease or transaminases > 1.5 X ULN Positive for Hepatitis B or C Major surgery within past 3 mos Cardiac insufficiency defined as functional Class II-Class IV Hx of malignancy within previous 5 years Participation in another investigational drug study within past 6 wks Serious or unstable medical or psychological condition Regular alcohol use > 1 drink per day Regular consumers of grapefruit juice or medications known to be metabolized by CYP 3A4 Use of other lipid-lowering meds (washout permitted) Acute CVD Diabetes Mellitus Fasting glucose >110 mg/dL BMI -/> 40 kg/m2 Significant gastrointestinal symptoms such as IBS Use of fish oils, niacin, herbal wt. loss products (washout permitted)

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>2.5 mg AEGR 733 plus atorvastatin 20 mg weeks 1-4 followed by 5 mg AEGR 733 plus atorvastatin 20 mg weeks 5-8 | Drug: AEGR-733<br>* 2.5 mg AEGR-733 capsules, daily dosing, 4 weeks followed by 5 mg AEGR-733 capsules, daily dosing, 4 weeks<br>|
| Active Comparator: 1<br>Following 35-day washout + diet run-in, subjects receive atorvastatin 20 mg for 8 wks. | Drug: Atorvastatin<br>* atorvastatin 20 mg tablets, daily dosing, for 8 weeks.<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in LDL-C After 8 Weeks of Therapy |  | Baseline and 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Changes in LDL-C at Week 4 + Baseline Serum Lipoproteins (TC, Non-HDL, VLDL, TGs, HDL-C, Apolopoproteins A1 and B), High Sensitivity C-reactive Protein and Change in Body Weight. |  | Baseline and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperlipidemia