Clinical trial NCT00943306: Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Familial Hypercholesterolemia
Keywords: Homozygous
Familial
Hypercholesterolemia
MTP
Apheresis
lomitapide
Homozygous Familial Hypercholesterolemia (HoFH)
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-07-22
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 126
Secondary outcomes:
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 174
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 222
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 246
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 270
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Week 294
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 126
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 174
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 222
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 246
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 270
measure: Percent Change in Total Cholesterol
timeFrame: Baseline and Week 294
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 126
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 174
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 222
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 246
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 270
measure: Percent Change in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 294
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 126
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 174
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 222
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 246
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 270
measure: Percent Change in Triglycerides
timeFrame: Baseline and Week 294
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 126
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 174
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 222
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 246
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 270
measure: Percent Change in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 294
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 126
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 174
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 222
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 246
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 270
measure: Percent Change in Very Low Density Lipoprotein Cholesterol (VLDL-C)
timeFrame: Baseline and Week 294
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 126
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 174
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 222
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 246
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 270
measure: Percent Change in Lp(a)
timeFrame: Baseline and Week 294
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 126
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 174
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 222
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 246
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 270
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 294
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 126
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 174
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 222
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 246
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 270
measure: Percent Change in Apolipoprotein AI (Apo AI)
timeFrame: Baseline and Week 294
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: Lipid Clinic and University of Montreal Community Genomic Medicine Center
state: Quebec
city: Ferrara
country: Italy
facility: Medicina Interna Universitaria
state: Sicily
city: Palermo
country: Italy
facility: Dipartimento di Medicina Clinica e Delle Patologie Emergenti
state: Sicily
city: Milano
country: Italy
facility: Centro Universitario Dislipidemie
city: Roma
country: Italy
facility: DAI Ematologia, Oncologia, Anatomia Patologica e Medicina
city: Bloemfontein
country: South Africa
facility: Cardiology Research
city: Cape town
country: South Africa
facility: University of Capetown
Study officials:
affiliation: University of Pennsylvania
name: Marina Cuchel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aegerion Pharmaceuticals, Inc.
name: Mark Sumeray, MD
role: STUDY_CHAIR
References:
citation: 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.
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