Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
Condition: Homozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: Lomitapide
Intervention description: Oral administration with escalating doses administered once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

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)].
    

Eligibility 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.