Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia

Study Overview
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Brief Summary
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This was a long term follow on study to assess the continued long term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia.

Detailed Description
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This was a phase III open label clinical trial to evaluate the long-term efficacy and safety of lomitapide at the maximum tolerated dose (for each patient) established during the clinical trial 733-005/UP1002. Subjects completing the 78-week treatment period in study 733-005/UP1002 who have not met any of the stopping criteria will be eligible to participate in 733-012. The treatment period continued until a decision was made by the local competent authority regarding marketing authorization. Lomitapide will be given orally once daily. Patient specific doses will be carried forward from 733-005/UP1002, but will not exceed the maximum tolerated dose the patient received during 733-005 /UP1002. The maximum dose for any patient was 80 mg/day. There was no reference therapy in this trial. The effects of the study drug were compared to baseline data (from 733-005/UP1002). Concomitant lipid-lowering therapy including plasmapheresis or LDL apheresis is permitted. Note that hereafter, Week 0 in Study 733-005/UP1002 will be referred to as Baseline and Week 48 in Study AEGR-733-012 will be referred to as Week 126 (of overall treatment).

Official Title
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A Phase III, Long Term, Open Label, Follow on Study of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor 'Lomitapide' (LOMITAPIDE) in Patients With Homozygous Familial Hypercholesterolemia

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: lomitapide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed UP1002 or 733-005. Willing and able to provide consent and comply with the requirements of the study protocol. Exclusion Criteria: Met any of the stopping rules for study discontinuation at the final visit of study UP1002 or 733-005.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lomitapide<br>Maximum tolerated dose of lomitapide in addition to existing lipid lowering therapy including plasmapheresis or lipid apheresis. | Drug: lomitapide<br>* 5-60 mg po every day<br>* Other names: BMS-201038;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) | Percent change in Low Density Lipoprotein Cholesterol (LDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Total Cholesterol | Percent change in Total Cholesterol from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Apolipoprotein B (Apo B) | Percent change in Apolipoprotein B (Apo B) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Triglycerides | Percent change in Triglycerides from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Percent change in Non High Density Lipoprotein Cholesterol (Non-HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C) | Percent change in Very Low Density Lipoprotein Cholesterol (VLDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Lp(a) | Percent change in Lp(a) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) | Percent change in High Density Lipoprotein Cholesterol (HDL-C) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 126 (Week 48 in Study AEGR-733-012). | Baseline and Week 126 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 174 (Week 96 in Study AEGR-733-012). | Baseline and Week 174 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 222 (Week 144 in Study AEGR-733-012). | Baseline and Week 222 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 246 (Week 168 in Study AEGR-733-012). | Baseline and Week 246 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 270 (Week 192 in Study AEGR-733-012). | Baseline and Week 270 | 
| Percent Change in Apolipoprotein AI (Apo AI) | Percent change in Apolipoprotein AI (Apo AI) from Baseline (Week 0 of Study 733-005/UP1002) to Week 294 (Week 216 in Study AEGR-733-012). | Baseline and Week 294 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apheresis, Homozygous, Familial, Hypercholesterolemia, MTP, lomitapide, Homozygous Familial Hypercholesterolemia (HoFH)