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

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

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

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: placebo; Drug: AEGR-733; Drug: AEGR-733 and atorvastatin; Drug: AEGR-733 and fenofibrate; Drug: AEGR-733 and ezetimibe

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.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92128
      • Scripps Clinic
    • Santa Rosa, California, United States, 95405
      • Radiant Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20003
      • Medstar Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Radiant Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • LMARC
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
    • Baltimore, Maryland, United States, 21209
      • Health Trends Research
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Univ. School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • San Antonio, Texas, United States, 78229
      • DGD Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Aegerion Pharmaceuticals, Inc.
• Investigators: Study Director: William Sasiela, PhD, Aegerion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 16, 2007
• First Posted (Estimate): November 19, 2007

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: LDL; hepatic fat
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Fenofibrate; Ezetimibe
• Other Study ID Numbers: AEGR-733-004