Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor

• Status: Completed
• Trial end date: 2004-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the safety and tolerability of 4 doses of lomitapide (AEGR-733; BMS-201038) given as an initial low dose and then escalated through an additional 3 dose levels over a 16-week period.

The secondary objectives of this study included the evaluation of the pharmacodynamics of lomitapide based on:

• Percent change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, and very low density lipoprotein cholesterol (VLDL-C) concentrations at the end of each 4-week dosing period compared to the Baseline value of each parameter at the end of the previous dose phase(s).

• Changes in other plasma lipoproteins: apolipoproteins (apo B, apo AI, apo AII, apo CIII, apo E) and lipoprotein a [Lp(a)].

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Aegerion Pharmaceuticals, Inc.
• Collaborators: Doris Duke Charitable Foundation; University of Pennsylvania

Criteria

Inclusion Criteria:

1. Males and females ≥13 years of age

2. Clinical diagnosis of HoFH AND one of the following (a, b, or c):

• Documented functional mutation in both LDL receptor alleles, OR

• Skin fibroblast LDL receptor activity <20% of normal, OR

• TC >500 mg/dL AND triglycerides < 300 mg/dL AND both parents with documented TC >250 mg/dL

3. Body weight ≥40 kg

4. Negative screening pregnancy test if female of child-bearing potential

5. Subjects must be willing and able to comply with all study-related procedures

6. Subjects must be willing and able to go off all lipid-lowering medications, dietary supplements (psyllium preparations) and LDL apheresis within 4 weeks prior to the Baseline visit until the end of the study.

Exclusion Criteria:

1. Uncontrolled hypertension defined as: systolic blood pressure >180 mmHg, diastolic blood pressure >95 mmHg

2. History of chronic renal insufficiency (serum creatinine >2.5 mg/dL)

3. History of liver disease or abnormal LFTs at screening (>3x upper limit of normal [ULN])

4. Any major surgical procedure occurring < 3 months prior to the screening visit

5. Cardiac insufficiency defined by the New York Heart Association classification as functional Class III or Class IV

6. History of a non-skin malignancy within the previous 5 years

7. History of alcohol or drug abuse

8. Participation in an investigational drug study within 6 weeks prior to the screening visit

9. Serious or unstable medical or psychological conditions that, in the opinion of the Investigator, would compromise the patient's safety or successful participation in the study.