Coronary Heart Disease, Hypercholesterolemia
Conditions
Brief summary
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.
Detailed 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.
Interventions
DRUGMipomersen
200 mg (1 mL), weekly subcutaneous injections for 26 weeks
DRUGPlacebo
1 mL weekly subcutaneous injections for 26 weeks
Sponsors
Ionis Pharmaceuticals, Inc.
Kastle Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| LDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Apo-B at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
| Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. |
Countries
Canada, Czechia, Germany, South Africa, United Kingdom, United States
Participant flow
Pre-assignment details
One hundred and four patients were screened and 58 randomized in a 2:1 treatment arm ratio.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Weekly subcutaneous injections for 26 weeks | 19 |
| Mipomersen 200 mg weekly subcutaneous injections for 26 weeks | 39 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Other | 1 | 2 |
| Follow-up Period | Protocol non-compliance | 0 | 1 |
| Follow-up Period | Withdrawal by Subject | 0 | 2 |
| Treatment Period | Adverse Event | 1 | 8 |
| Treatment Period | Other | 0 | 1 |
| Treatment Period | Protocol non-compliance | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Mipomersen | Total |
|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 13.5 | 51.8 years STANDARD_DEVIATION 14.3 | 50.5 years STANDARD_DEVIATION 14 |
| Alcohol Use Current | 7 participants | 27 participants | 34 participants |
| Alcohol Use Never | 8 participants | 7 participants | 15 participants |
| Alcohol Use Non-current | 4 participants | 5 participants | 9 participants |
| Body Mass Index | 29.9 kg/m^2 STANDARD_DEVIATION 4.1 | 28.4 kg/m^2 STANDARD_DEVIATION 5.35 | 28.9 kg/m^2 STANDARD_DEVIATION 4.98 |
| Ethnicity Hispanic or Latino | 0 participants | 0 participants | 0 participants |
| Ethnicity Not Hispanic or Latino | 19 participants | 39 participants | 58 participants |
| Metabolic syndrome No | 10 participants | 25 participants | 35 participants |
| Metabolic syndrome Yes | 9 participants | 14 participants | 23 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Multiple | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Other | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White | 16 participants | 33 participants | 49 participants |
| Sex: Female, Male Female | 12 Participants | 21 Participants | 33 Participants |
| Sex: Female, Male Male | 7 Participants | 18 Participants | 25 Participants |
| Tobacco Use Current | 5 participants | 4 participants | 9 participants |
| Tobacco Use Never | 7 participants | 24 participants | 31 participants |
| Tobacco Use Non-current | 7 participants | 11 participants | 18 participants |
| Waist/hip ratio | 0.94 ratio STANDARD_DEVIATION 0.06 | 0.92 ratio STANDARD_DEVIATION 0.09 | 0.93 ratio STANDARD_DEVIATION 0.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 19 | 39 / 39 |
| serious Total, serious adverse events | 0 / 19 | 6 / 39 |
Outcome results
Primary
LDL-C at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | LDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 249.4 mg/dL | Standard Deviation 84.3 |
| Placebo | LDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 263.9 mg/dL | Standard Deviation 102 |
| Mipomersen | LDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 276.1 mg/dL | Standard Deviation 72.1 |
| Mipomersen | LDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 174.9 mg/dL | Standard Deviation 82.8 |
Primary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point
LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set (FAS). The FAS, which represents the practically-feasible intent-to-treat (ITT) population as delineated in ICH Guideline E9, consists of treated participants with a valid baseline and at least one post-baseline LDL-C measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point | 12.5 percentage of baseline | Standard Deviation 46.87 |
| Mipomersen | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point | -35.9 percentage of baseline | Standard Deviation 24.71 |
Comparison: Based upon prior clinical study experience with mipomersen, it was estimated that the standard deviation of the percent change in LDL-C was approximately 22%. With 15 patients in the control group and 30 patients in the mipomersen-treated group, this study would have at least 80% power to detect a 20 percentage point difference between the 2 treatment groups. Enrollment was to be conducted such that at least 51 patients were randomized to allow for potential exclusions from an analysis set.p-value: <0.001t-test, 2 sided
Secondary
Apo-B at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apo-B at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 182.8 mg/dL | Standard Deviation 48.6 |
| Placebo | Apo-B at Baseline and the Primary Efficacy Time Point (PET) | PET | 193.7 mg/dL | Standard Deviation 54.2 |
| Mipomersen | Apo-B at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 202.1 mg/dL | Standard Deviation 49.1 |
| Mipomersen | Apo-B at Baseline and the Primary Efficacy Time Point (PET) | PET | 126.8 mg/dL | Standard Deviation 49.6 |
Secondary
Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 277.5 mg/dL | Standard Deviation 88.3 |
| Placebo | Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 296.7 mg/dL | Standard Deviation 103.8 |
| Mipomersen | Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 305.6 mg/dL | Standard Deviation 78.3 |
| Mipomersen | Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 198.1 mg/dL | Standard Deviation 85.3 |
Secondary
Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)
Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) | 14.17 percentage of baseline | Standard Deviation 47.75 |
| Mipomersen | Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) | -33.95 percentage of baseline | Standard Deviation 23.8 |
p-value: <0.001t-test, 2 sided
Secondary
Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)
Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) | 11.13 percentage of baseline | Standard Deviation 34.74 |
| Mipomersen | Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) | -28.31 percentage of baseline | Standard Deviation 20.43 |
p-value: <0.001t-test, 2 sided
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point
Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point | 11.41 percentage of baseline | Standard Deviation 36.8 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point | -35.88 percentage of baseline | Standard Deviation 22.95 |
p-value: <0.001t-test, 2 sided
Secondary
Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 320.6 mg/dL | Standard Deviation 87.2 |
| Placebo | Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | PET | 341.5 mg/dL | Standard Deviation 100.5 |
| Mipomersen | Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 356.8 mg/dL | Standard Deviation 77 |
| Mipomersen | Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | PET | 251.5 mg/dL | Standard Deviation 82.2 |
Other Pre-specified
Apo-A1 at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 139.2 mg/dL | Standard Deviation 32.6 |
| Placebo | Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | PET | 140.7 mg/dL | Standard Deviation 34.2 |
| Mipomersen | Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 154.9 mg/dL | Standard Deviation 31.4 |
| Mipomersen | Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | PET | 147.9 mg/dL | Standard Deviation 27 |
Other Pre-specified
Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)
LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | 1.9 percentage of baseline |
| Mipomersen | Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | -41.8 percentage of baseline |
p-value: <0.001Wilcoxon rank sum test
Other Pre-specified
HDL-C at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 43.1 mg/dL | Standard Deviation 11.6 |
| Placebo | HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 44.8 mg/dL | Standard Deviation 16.3 |
| Mipomersen | HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 51.1 mg/dL | Standard Deviation 15.1 |
| Mipomersen | HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 53.4 mg/dL | Standard Deviation 16.7 |
Other Pre-specified
Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 32.4 mg/dL | Standard Deviation 28.5 |
| Placebo | Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | PET | 32.1 mg/dL | Standard Deviation 28.1 |
| Mipomersen | Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 61.3 mg/dL | Standard Deviation 68.4 |
| Mipomersen | Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | PET | 43.3 mg/dL | Standard Deviation 54.3 |
Other Pre-specified
Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)
HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | 3.16 percentage of baseline | Standard Deviation 16.5 |
| Mipomersen | Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | 5.78 percentage of baseline | Standard Deviation 21.25 |
p-value: 0.647t-test, 2 sided
Other Pre-specified
Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)
Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) | -1.46 percentage of baseline | Standard Deviation 25.74 |
| Mipomersen | Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) | -32.65 percentage of baseline | Standard Deviation 32.98 |
p-value: <0.001t-test, 2 sided
Other Pre-specified
Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)
Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) | 26.50 percentage of baseline | Standard Deviation 60.61 |
| Mipomersen | Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) | -8.71 percentage of baseline | Standard Deviation 40.1 |
p-value: 0.034t-test, 2 sided
Other Pre-specified
Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)
VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) | 25.13 percentage of baseline | Standard Deviation 58.66 |
| Mipomersen | Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) | -9.36 percentage of baseline | Standard Deviation 39.57 |
p-value: <0.032t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)
Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) | 1.75 percentage of baseline | Standard Deviation 14.33 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) | -3.04 percentage of baseline | Standard Deviation 15.76 |
p-value: 0.278t-test, 2 sided
Other Pre-specified
Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 5.85 ratio |
| Placebo | Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 5.89 ratio |
| Mipomersen | Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 5.21 ratio |
| Mipomersen | Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 3.05 ratio |
Other Pre-specified
Triglycerides at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 140.3 mg/dL | Standard Deviation 49.8 |
| Placebo | Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | PET | 164.5 mg/dL | Standard Deviation 61.2 |
| Mipomersen | Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 142.2 mg/dL | Standard Deviation 86 |
| Mipomersen | Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | PET | 116.3 mg/dL | Standard Deviation 63.3 |
Other Pre-specified
VLDL-C at Baseline and the Primary Efficacy Time Point (PET)
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 28.1 mg/dL | Standard Deviation 9.9 |
| Placebo | VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 32.8 mg/dL | Standard Deviation 12.3 |
| Mipomersen | VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | Baseline | 29.1 mg/dL | Standard Deviation 20 |
| Mipomersen | VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | PET | 23.2 mg/dL | Standard Deviation 12.6 |