Safety and Efficacy of Mipomersen (ISIS 301012) As Add-on Therapy in High Risk Hypercholesterolemic Patients - Full Text View

Purpose

The purpose of this study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in patients with high cholesterol who are on a maximally tolerated dose of statin and who have a diagnosis that puts them at least at high risk of coronary heart disease (CHD).

Condition	Intervention	Phase
Hypercholesterolemia Coronary Heart Disease	Drug: Mipomersen sodium Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) as Add-on Therapy in High Risk Hypercholesterolemic Patients

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Coronary Artery Disease Heart Diseases

Drug Information available for: Mipomersen sodium Mipomersen

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. LDL-C was obtained using Friedewald's calculation for patients with triglycerides ≤400 mg/dL and was directly measured by the central laboratory using ultracentrifugation for patients with triglycerides >400 mg/dL. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Secondary Outcome Measures:

Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Apolipoprotein B at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Total Cholesterol at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Other Outcome Measures:

Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Triglycerides at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
High-density lipoprotein cholesterol (HDL-C) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Lipoprotein (a) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Very low density lipoprotein (VLDL) cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol was measured at Baseline and the post-baseline visit closest to 14 days after the last dose of study treatment.
Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point [ Time Frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose). ] [ Designated as safety issue: No ]
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Enrollment:	158
Study Start Date:	November 2008
Study Completion Date:	October 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Participants received placebo subcutaneous injection once a week for 26 weeks.	Drug: Placebo 1 mL matching placebo (i.e., vehicle consisting of 9 mg of sodium chloride, 0.004 mg of riboflavin, filled to 1 mL with water).
Experimental: Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.	Drug: Mipomersen sodium 200 mg/mL Other Names: ISIS 301012 Kynamro™

Detailed Description:

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for 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 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 patients with high cholesterol who are at high risk for CHD and who are already on the maximally tolerated dose of statin.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Participants who finished treatment or who discontinued prematurely from the study for any reason were assessed for safety for 24 weeks after the last study drug dose.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of hypercholesterolemia (LDL-C ≥ 100 mg/dL)
At high risk of CHD
On stable, maximally tolerated statin therapy 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, liver disease, cancer, type I diabetes.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770146

Show 62 Study Locations

Sponsors and Collaborators

Genzyme

Isis Pharmaceuticals

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT00770146 History of Changes
Other Study ID Numbers:	301012-CS12
Study First Received:	October 8, 2008
Results First Received:	February 15, 2013
Last Updated:	February 15, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Hypercholesterolemia
Cardiovascular Diseases
Arteriosclerosis

Arterial Occlusive Diseases
Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on May 21, 2013