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A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)

This study has been completed.
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc. Identifier:
First received: August 6, 2008
Last updated: January 15, 2014
Last verified: January 2013
The goal of this trial is to study the effects of AEGR-733 on LDL cholesterol, other lipids as well as measures of safety over the long-term.

Condition Intervention Phase
Homozygous Familial Hypercholesterolemia
Drug: AEGR-733
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor AEGR-733 in Patients With Homozygous Familial Hypercholesterolemia on Current Lipid-lowering Therapy

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in LDL-C

Secondary Outcome Measures:
  • Percent Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in TC

  • Percent Change From Baseline for Apolipoprotein B (Apo B) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline for Apo B

  • Percent Change From Baseline in Triglycerides [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in triglycerides

  • Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in HDL-C

  • Percent Change From Baseline in Non-HDL-C [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in non-HDL-C

  • Percent Change From Baseline in Apolipoprotein AI (Apo AI) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in Apo AI

  • Absolute Change From Baseline in Hepatic Fat Percent [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in hepatic fat percent

  • Absolute Change From Baseline in Alanine Aminotransferase (ALT) [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in ALT

  • Absolute Change From Baseline in Aspartate Aminotransferase (AST) [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in AST

  • Absolute Change From Baseline in Total Bilirubin [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in total bilirubin

  • Absolute Change From Baseline in Weight [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in weight

Enrollment: 29
Study Start Date: December 2007
Study Completion Date: October 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEGR-733 Drug: AEGR-733
5-80 mg daily by mouth for 1.5 yrs
Other Names:
  • lomitapide
  • BMS-201038

Detailed Description:

Homozygous familial hypercholesterolemia (FH) is a serious life-threatening genetic disease. Total plasma cholesterol levels are generally over 500 mg/dl and markedly premature cardiovascular disease is the major consequence. Untreated, most patients develop atherosclerosis before age 20 and generally do not survive past age 30. The primary goal of therapy involves reducing cholesterol (specifically, LDL cholesterol) and preventing coronary artery disease. Unfortunately, patients with homozygous FH are minimally responsive or unresponsive to available drug therapy and thus there are limited treatment options. The current standard of care is LDL apheresis, a physical method of removing the plasma of LDL cholesterol which can transiently reduce cholesterol by more than 50%. However, there is rapid re-accumulation of LDL cholesterol in plasma, and therefore apheresis has to be repeated frequently (every 1-2 weeks) and requires 2 separate sites for IV access. Although anecdotally this procedure may delay the onset of atherosclerosis, it is laborious, expensive, and not readily available. Furthermore, although it is a procedure that is generally well tolerated, the fact that it needs frequent repetition and IV access can be challenging for many of these young patients. Therefore, there is a tremendous unmet medical need for new medical therapies for this orphan disease.

AEGR-733 is a novel oral therapeutic agent for hypercholesterolemia. Its mechanism involves inhibition of microsomal triglyceride transfer protein, resulting in a reduction of LDL cholesterol. Earlier studies in patients with homozygous FH reveal AEGR-733 is highly effective in lowering LDL cholesterol, yet long term safety and efficacy need to be established.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males and females at least 18 years of age
  2. Diagnosis of functional homozygous FH by at least one (a-c) of the following clinical criteria:

    • documented functional mutation(s) in both LDL receptor alleles or alleles known to affect LDL receptor functionality OR
    • skin fibroblast LDL receptor activity less than 20% normal OR
    • untreated TC greater than 500 mg/dL AND TG less then 300 mg/dL AND both parents have documented TC greater than 250 mg/dL
  3. Concurrent lipid lowering medication/apheresis must be stable for at least 6 weeks before the baseline visit and must remain stable for the first 26 weeks.
  4. Body weight at least 40 kg and less than 136 kg
  5. Negative screening pregnancy test if female of child-bearing potential (females of child-bearing potential and all males must be following a medically accepted form of contraception)
  6. Subjects must be willing to comply with all study-related procedures

Exclusion Criteria:

  1. Uncontrolled hypertension
  2. History of chronic renal insufficiency
  3. History of biopsy proven cirrhosis or abnormal LFTs at screening (AST or ALT greater than 2 x upper limit of normal and/or Total Bilirubin greater than or equal to 1.5 mg/dl unless patient has unconjugated hyperbilirubinemia due to Gilbert's syndrome)
  4. Chronic hepatitis B or chronic hepatitis C
  5. Any major surgical procedure occurring less than 3 months prior to the screening visit
  6. Cardiac insufficiency defined by the NYHA classification as functional Class III or Class IV
  7. Previous organ transplantation
  8. History of a non-skin malignancy within the previous 3 years
  9. Male subjects reporting more than 2 drinks per day or females reporting more than 1 drink per day (1 drink= 12 oz beer, 1 oz hard liquor, 5 oz wine).
  10. Participation in an investigational drug study within 6 weeks prior to the screening visit
  11. Known significant gastrointestinal bowel disease or malabsorption such as inflammatory bowel disease or chronic pancreatitis requiring use of daily pancreatic enzymes.
  12. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
  13. Certain prohibited medications known to be potentially hepatotoxic, especially those that can induce microvesicular or macrovesicular steatosis. These include but are not limited to: accutane, amiodarone, heavy acetaminophen use (4g/day greater than 3 x q week), methotrexate, tetracyclines,and tamoxifen
  14. Documented diagnosis of any of the following pulmonary conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis
  15. Documented diagnosis of any of the following liver diseases: Nonalcoholic Steatohepatitis, Alcoholic liver disease, Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, alpha 1 anti-trypsin deficiency.
  16. Current use of corticosteroids or betaine
  Contacts and Locations
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Please refer to this study by its identifier: NCT00730236

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Canada, Ontario
Robarts Research Institute
London, Ontario, Canada, N6A 5K8
Canada, Quebec
Lipid Clinic and University of Montreal Community Genomic Medicine Center
Chicoutimi, Quebec, Canada, G7H 5H6
Dipartimento di Medicina Clinica e Della Patalogie Emergenti
Palermo, Sicily, Italy
Medicina Interna Universitaria
Ferrara, Italy
Centro Universitario Dislipidemie
Milano, Italy
Dipartimento di Clinica e Terapia Medica
Roma, Italy
South Africa
Cardiology Research
Bloemfontein, South Africa, 9300
University of Capetown
Cape town, South Africa, 7925
Sponsors and Collaborators
Aegerion Pharmaceuticals, Inc.
FDA Office of Orphan Products Development
Study Director: Mark Sumeray, MD Aegerion Pharmaceuticals, Inc.
Principal Investigator: Marina Cuchel, MD, PhD Univerity of Pennsylvania
  More Information

Cuchel M, Meagher E, Marais AD, Abstract 1077: A phase III study of microsomal triglyceride transfer protein inhibitor lomitapide (AEGR-733) in patients with homozygous familial hypercholesterolemia: interim results at 6 months. Circulation, Nov 2009; 120: S441

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Aegerion Pharmaceuticals, Inc. Identifier: NCT00730236     History of Changes
Obsolete Identifiers: NCT00603161
Other Study ID Numbers: 733-005 / UP1002
Study First Received: August 6, 2008
Results First Received: January 18, 2013
Last Updated: January 15, 2014

Additional relevant MeSH terms:
Hyperlipoproteinemia Type II
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias processed this record on May 22, 2017