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Trial record 6 of 19 for:    MIPOMERSEN

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

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ClinicalTrials.gov Identifier: NCT00770146
Recruitment Status : Completed
First Posted : October 9, 2008
Results First Posted : March 20, 2013
Last Update Posted : September 9, 2016
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

Tracking Information
First Submitted Date  ICMJE October 8, 2008
First Posted Date  ICMJE October 9, 2008
Results First Submitted Date  ICMJE February 15, 2013
Results First Posted Date  ICMJE March 20, 2013
Last Update Posted Date September 9, 2016
Study Start Date  ICMJE November 2008
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2013)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
Percent change in LDL-C from Baseline to Week 28 [ Time Frame: Week 28 ]
Change History Complete list of historical versions of study NCT00770146 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2013)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
  • Percent change in apoB, from Baseline to Week 28 [ Time Frame: Week 28 ]
  • Percent change in total cholesterol from Baseline to week 28 [ Time Frame: week 28 ]
  • Percent change in non-HDL-C from Baseline to Week 28 [ Time Frame: week 28 ]
  • Percent change in triglycerides from Baseline to Week 28 [ Time Frame: week 28 ]
  • Percent change in HDL-C from Baseline to Week 28 [ Time Frame: Week 28 ]
  • Percent change in Lp(a) from Baseline to Week 28 [ Time Frame: Week 28 ]
Current Other Pre-specified Outcome Measures
 (submitted: February 15, 2013)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Mipomersen (ISIS 301012) As Add-on Therapy in High Risk Hypercholesterolemic Patients
Official Title  ICMJE 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
Brief Summary 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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypercholesterolemia
  • Coronary Heart Disease
Intervention  ICMJE
  • Drug: Mipomersen sodium
    200 mg/mL
    Other Names:
    • ISIS 301012
    • Kynamro™
  • 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).
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants received placebo subcutaneous injection once a week for 26 weeks.
    Intervention: Drug: Placebo
  • Experimental: Mipomersen
    Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
    Intervention: Drug: Mipomersen sodium
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2010)
158
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2008)
180
Actual Study Completion Date  ICMJE October 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00770146
Other Study ID Numbers  ICMJE 301012-CS12
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kastle Therapeutics, LLC
Study Sponsor  ICMJE Kastle Therapeutics, LLC
Collaborators  ICMJE Ionis Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Kastle Therapeutics, LLC
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP