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

Condition(s) targeted: Hypercholesterolemia

Intervention: Atorvastatin (Drug); AEGR-733 (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Aegerion Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Steven Belknap, MD, Study Director, Affiliation: Medical Monitor at Radiant Research

Overall contact:
Kathy Scott, Phone: 513-478-4478, Email: kathyscott@radiantresearch.com

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.

Official title: 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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Percent change in LDL-C after 8 weeks of therapy

Secondary outcome: Percent changes in LDL-C at week 4 + baseline serum lipoproteins (TC, non-HDL, VLDL, TGs, HDL-C, apolipoproteins A1 and B), high sensitivity C-reactive protein, change in body weight,overall safety and tolerability.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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)

Kathy Scott, Phone: 513-478-4478, Email: kathyscott@radiantresearch.com

Linda Murray, DO - Radiant Research, Pinellas Park, Florida 33781, United States; Recruiting
Linda Murray, DO, Principal Investigator

Sheila Rodstein, MD, Edina, Minnesota 55435, United States; Recruiting
Sheila Rodstein, MD, Principal Investigator

Dennis McCluskey, MD - Radiant Research, Mogadore, Ohio 44260, United States; Recruiting
Dennis McCluskey, MD, Principal Investigator

William Jennings, MD - Radiant Research, San Antonio, Texas 78229, United States; Recruiting
William Jennings, MD, Principal Investigator

Michele Reynolds, MD, Dallas, Texas 75231, United States; Recruiting
Michele Reynolds, MD, Principal Investigator

Starting date: May 2008
Ending date: September 2008
Last updated: June 3, 2008