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

Aegerion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hyperlipidemia

Treatments: Drug: placebo; Drug: AEGR-733 and fenofibrate; Drug: AEGR-733 and atorvastatin; Drug: AEGR-733; Drug: AEGR-733 and ezetimibe

Study type: Interventional

Funder types: Industry

Identifiers

NCT00559962

AEGR-733-004

Details and patient eligibility

About

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

Full 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.

Enrollment: 260 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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260 participants in 8 patient groups, including a placebo group

1

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: placebo

2

Active Comparator group

Description:

2.5 mg AEGR-733

Treatment:

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

3

Active Comparator group

Description:

5 mg AEGR-733

Treatment:

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

4

Active Comparator group

Description:

7.5 mg AEGR-733

Treatment:

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

5

Active Comparator group

Description:

10 mg AEGR-733

Treatment:

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

Drug: AEGR-733

6

Active Comparator group

Description:

5 mg AEGR-733 + 20 mg atorvastatin

Treatment:

Drug: AEGR-733 and atorvastatin

7

Active Comparator group

Description:

5 mg AEGR-733 + 145 mg fenofibrate

Treatment:

Drug: AEGR-733 and fenofibrate

8

Active Comparator group

Description:

5 mg AEGR-733 + 10 mg ezetimibe

Treatment:

Drug: AEGR-733 and ezetimibe