Clinical trial NCT00559962: Evaluate Low Doses of AEGR-733 on Hepatic Fat Accumulation by MRS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperlipidemia
Keywords: LDL
hepatic fat
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2007-11-19
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change From Baseline in Percent Hepatic Fat
timeFrame: Baseline and 12 weeks on study drug
Secondary outcomes:
measure: Absolute Change From Baseline in Percent Hepatic Fat
timeFrame: Baseline and 12 weeks on study drug
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Scripps Clinic
state: California
city: Santa Rosa
country: United States
facility: Radiant Research
state: California
city: Washington
country: United States
facility: MedStar Research Institute
state: District of Columbia
city: Chicago
country: United States
facility: Radiant Research
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: LMARC
state: Kentucky
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Baltimore
country: United States
facility: Health Trends Research
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Saint Louis
country: United States
facility: Washington Univ. School of Medicine
state: Missouri
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: San Antonio
country: United States
facility: dgd Research
state: Texas
Study officials:
affiliation: Aegerion Pharmaceuticals, Inc.
name: William Sasiela, PhD
role: STUDY_DIRECTOR
References: