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

This study has been completed.
Sponsor:
Information provided by:
Aegerion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00559962
First received: November 15, 2007
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Hyperlipidemia
Drug: AEGR-733
Drug: placebo
Drug: AEGR-733 and atorvastatin
Drug: AEGR-733 and fenofibrate
Drug: AEGR-733 and ezetimibe
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Aegerion Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Absolute Change From Baseline in Percent Hepatic Fat [ Time Frame: Baseline and 12 weeks on study drug ] [ Designated as safety issue: Yes ]
    Absolute change from Baseline in percent hepatic fat


Secondary Outcome Measures:
  • Absolute Change From Baseline in Percent Hepatic Fat [ Time Frame: Baseline and 12 weeks on study drug ] [ Designated as safety issue: Yes ]
    Absolute change from Baseline in percent hepatic fat


Enrollment: 260
Study Start Date: October 2007
Study Completion Date: November 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Placebo
Drug: placebo
3 capsules each evening for each 4-week period
Other Name: Placebo
Active Comparator: 2
2.5 mg AEGR-733
Drug: AEGR-733
3 capsules each evening for each 4-week period
Other Name: AEGR-733
Active Comparator: 3
5 mg AEGR-733
Drug: AEGR-733
3 capsules each evening for each 4-week period
Other Name: AEGR-733
Active Comparator: 4
7.5 mg AEGR-733
Drug: AEGR-733
3 capsules each evening for each 4-week period
Other Name: AEGR-733
Active Comparator: 5
10 mg AEGR-733
Drug: AEGR-733
3 capsules each evening for each 4-week period
Other Name: AEGR-733
Active Comparator: 6
5 mg AEGR-733 + 20 mg atorvastatin
Drug: AEGR-733 and atorvastatin
3 capsules each evening for each 4-week period
Other Name: AEGR-733 and atorvastatin
Active Comparator: 7
5 mg AEGR-733 + 145 mg fenofibrate
Drug: AEGR-733 and fenofibrate
3 capsules each evening for each 4-week period
Other Name: AEGR-733 and fenofibrate
Active Comparator: 8
5 mg AEGR-733 + 10 mg ezetimibe
Drug: AEGR-733 and ezetimibe
3 capsules each evening for each 4-week period
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559962

Locations
United States, California
Scripps Clinic
San Diego, California, United States, 92128
Radiant Research
Santa Rosa, California, United States, 95405
United States, District of Columbia
MedStar Research Institute
Washington, District of Columbia, United States, 20003
United States, Illinois
Radiant Research
Chicago, Illinois, United States, 60610
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
LMARC
Louisville, Kentucky, United States, 40213
United States, Maine
Maine Research Associates
Auburn, Maine, United States, 04210
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
Health Trends Research
Baltimore, Maryland, United States, 21209
United States, Missouri
Washington Univ. School of Medicine
St. Louis, Missouri, United States, 63110
United States, Ohio
Sterling Research Group
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Clinical Trial Network
Houston, Texas, United States, 77074
dgd Research
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Aegerion Pharmaceuticals, Inc.
Investigators
Study Director: William Sasiela, PhD Aegerion Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: William J Sasiela, PhD Chief Medical Officer, Aegerion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00559962     History of Changes
Other Study ID Numbers: 733-004
Study First Received: November 15, 2007
Results First Received: January 18, 2013
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Aegerion Pharmaceuticals, Inc.:
LDL
hepatic fat

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Ezetimibe
Fenofibrate
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014