Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

Kastle Therapeutics

Status and phase

Completed

Phase 3

Conditions

Coronary Heart Disease

Hypercholesterolemia

Treatments

Drug: Placebo

Drug: Mipomersen

Study type

Interventional

Funder types

Industry

Identifiers

NCT00794664

MIPO3500108

2008-006020-53 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in treating severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Full description

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (CHD).

Mipomersen is an antisense drug that reduces a protein in the liver cells called apolipoprotein B (Apo-B). Apo-B plays a role in producing low density lipoprotein cholesterol (LDL-C) (the "bad" cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. The purpose of this study is to determine whether mipomersen safely and effectively lowers LDL-C in severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Enrollment

58 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Fasting LDL-C ≥200 mg/dL (5.1 mmol/L) at screening and the presence of at least 1 of the following criteria:
- Myocardial infarction (MI)
- Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
- Coronary artery disease documented by angiography or any other accepted imaging technique
- Positive exercise test (≥1 mm ST-depression at maximal exercise or test terminated because of angina) or a perfusion defect (e.g., thallium or single photon emission computed tomography)
- Other clinical atherosclerotic diseases: peripheral artery disease, symptomatic carotid artery disease, abdominal aortic aneurysm
- Or, if alternative above were not met, fasting LDL-C ≥300 mg/dL (7.8 mmol/L)
On stable, maximally tolerated statin therapy for 8 weeks
On stable, medication from an additional class of hypolipidemic agents for 8 weeks.
On stable, low fat diet for 12 weeks
Stable weight for 6 weeks

Exclusion criteria

Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes
Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase