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

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

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.

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Drug: lomitapide

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5K8
      • Robarts Research Institute
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Lipid Clinic and University of Montreal Community Genomic Medicine Center
• Italy
  • Milano, Italy
    • Centro Universitario Dislipidemie
  • Roma, Italy
    • DAI Ematologia, Oncologia, Anatomia Patologica e Medicina
  • Sicily
    • Ferrara, Sicily, Italy
      • Medicina Interna Universitaria
    • Palermo, Sicily, Italy
      • Dipartimento di Medicina Clinica e Delle Patologie Emergenti
• South Africa
  • Bloemfontein, South Africa, 9300
    • Cardiology Research
  • Cape town, South Africa, 7925
    • University of CapeTown
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Completed UP1002 or 733-005.
2. Willing and able to provide consent and comply with the requirements of the study protocol.

Exclusion Criteria:

1. Met any of the stopping rules for study discontinuation at the final visit of study UP1002 or 733-005.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lomitapide; Maximum tolerated dose of lomitapide in addition to existing lipid lowering therapy including plasmapheresis or lipid apheresis.	Drug: lomitapide; 5-60 mg po every day; Other Names: AEGR-733; BMS-201038

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aegerion Pharmaceuticals, Inc.
• Investigators: Study Chair: Mark Sumeray, MD, Aegerion Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. doi: 10.1056/NEJMoa061189.
• Cuchel M, Meagher E, Marais AD, et.al. 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

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2009
• Primary Completion (Actual): September 17, 2012
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (Estimate): July 22, 2009

Study Record Updates

• Last Update Posted (Actual): June 13, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; Apheresis; Familial; Homozygous; MTP; lomitapide; Homozygous Familial Hypercholesterolemia (HoFH)
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: AEGR-733-012