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Completed

NCT Number: NCT00770146

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

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).

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Key information

Conditions

Hypercholesterolemia Cardiovascular Diseases Coronary Disease Coronary Heart Disease Dyslipidemias Heart Diseases Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Myocardial Ischemia Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Birmingham, Alabama, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

mipomersen sodium

Drug

200 mg/mL

Other names: ISIS 301012, Kynamro™

Placebo

Drug

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).

Primary outcomes

  1. 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).

    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.

  2. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Secondary outcomes

  1. 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).

    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.

  2. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  3. 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).

    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.

  4. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  5. 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).

    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.

  6. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Other outcomes

  1. 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).

    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.

  2. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  3. 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).

    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.

  4. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  5. 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).

    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.

  6. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  7. 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).

    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.

  8. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  9. 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).

    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.

  10. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  11. 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).

    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.

  12. 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).

    The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Sponsors and collaborators

Lead sponsor

Kastle Therapeutics, LLC

Industry

Collaborators

  • Ionis Pharmaceuticals, Inc.

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
Oct 9, 2008
Registry last updated
Sep 9, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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