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

Familial Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00943306
• Other study ID #: AEGR-733-012
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2009
• Est. completion date: December 1, 2014

Study information

• Verified date: May 2018
• Source: Aegerion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 1, 2014
• Est. primary completion date: September 17, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• lomitapide
5-60 mg po every day

Locations

Country	Name	City	State
Canada	Lipid Clinic and University of Montreal Community Genomic Medicine Center	Chicoutimi	Quebec
Canada	Robarts Research Institute	London	Ontario
Italy	Medicina Interna Universitaria	Ferrara	Sicily
Italy	Centro Universitario Dislipidemie	Milano
Italy	Dipartimento di Medicina Clinica e Delle Patologie Emergenti	Palermo	Sicily
Italy	DAI Ematologia, Oncologia, Anatomia Patologica e Medicina	Roma
South Africa	Cardiology Research	Bloemfontein
South Africa	University of Capetown	Cape town
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Aegerion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Italy,  South Africa, 

References & Publications (2)

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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