Coronary Heart Disease, Hypercholesterolemia
Conditions
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.
Interventions
200 mg/mL
DRUGPlacebo
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).
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point | 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 | 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 B at the Primary Efficacy Time Point | 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. |
| Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | 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 | 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. |
| Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point | 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 | 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 Triglycerides at the Primary Efficacy Time Point | 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. |
| Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | 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 | 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. |
| Triglycerides at Baseline and at the Primary Efficacy Time Point | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Countries
United States
Participant flow
Pre-assignment details
Five hundred and seventy-seven patients were screened and 158 patients were randomized at 43 study centers in a 2:1 ratio to receive mipomersen or placebo once a week for 26 weeks. 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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneous injection once a week for 26 weeks. | 52 |
| Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. | 105 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Adverse Event | 0 | 2 |
| Follow-up Period | Other | 4 | 5 |
| Follow-up Period | Withdrawal by Subject | 7 | 13 |
| Treatment Period | Adverse Event | 2 | 26 |
| Treatment Period | Other | 1 | 5 |
| Treatment Period | Protocol non-compliance | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 6 | 13 |
Baseline characteristics
| Characteristic | Placebo | Mipomersen | Total |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 9.5 | 59.3 years STANDARD_DEVIATION 10 | 59.3 years STANDARD_DEVIATION 9.8 |
| Alcohol use Current | 20 participants | 50 participants | 70 participants |
| Alcohol use Never | 20 participants | 31 participants | 51 participants |
| Alcohol use Non-current | 12 participants | 24 participants | 36 participants |
| Body Mass Index (BMI) | 30.0 kg/m^2 STANDARD_DEVIATION 4.42 | 30.7 kg/m^2 STANDARD_DEVIATION 4.61 | 30.4 kg/m^2 STANDARD_DEVIATION 4.55 |
| Cardiovascular history Abdominal aortic aneurysm | 1 participants | 0 participants | 1 participants |
| Cardiovascular history Angina | 5 participants | 9 participants | 14 participants |
| Cardiovascular history Carotid | 1 participants | 8 participants | 9 participants |
| Cardiovascular history CHD or other atherosclerotic disease | 24 participants | 58 participants | 82 participants |
| Cardiovascular history Coronary artery bypass graft surgery | 4 participants | 14 participants | 18 participants |
| Cardiovascular history Coronary artery disease without event | 6 participants | 14 participants | 20 participants |
| Cardiovascular history Coronary heart disease (CHD) | 21 participants | 52 participants | 73 participants |
| Cardiovascular history Myocardial infarction | 11 participants | 17 participants | 28 participants |
| Cardiovascular history Other clinical atherosclerotic disease | 3 participants | 11 participants | 14 participants |
| Cardiovascular history Percutaneous coronary intervention | 4 participants | 18 participants | 22 participants |
| Cardiovascular history Peripheral artery disease | 1 participants | 5 participants | 6 participants |
| Diabetic status at screening No | 22 participants | 47 participants | 69 participants |
| Diabetic status at screening Yes | 30 participants | 58 participants | 88 participants |
| Metabolic syndrome No | 12 participants | 32 participants | 44 participants |
| Metabolic syndrome Yes | 40 participants | 73 participants | 113 participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black | 11 participants | 20 participants | 31 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 participants | 16 participants | 25 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 43 participants | 89 participants | 132 participants |
| Race/Ethnicity, Customized Other race | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 40 participants | 83 participants | 123 participants |
| Sex: Female, Male Female | 23 Participants | 53 Participants | 76 Participants |
| Sex: Female, Male Male | 29 Participants | 52 Participants | 81 Participants |
| Tobacco use Current | 11 participants | 18 participants | 29 participants |
| Tobacco use Never | 22 participants | 56 participants | 78 participants |
| Tobacco use Non-current | 19 participants | 31 participants | 50 participants |
| Waist/hip ratio | 0.94 ratio STANDARD_DEVIATION 0.07 | 0.94 ratio STANDARD_DEVIATION 0.06 | 0.94 ratio STANDARD_DEVIATION 0.06 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 52 | 97 / 105 |
| serious Total, serious adverse events | 4 / 52 | 7 / 105 |
Outcome results
Primary
Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point | Baseline | 112 mg/dL | Inter-Quartile Range 38.6 |
| Placebo | Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 109 mg/dL | Inter-Quartile Range 35.1 |
| Mipomersen | Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point | Baseline | 116 mg/dL | Inter-Quartile Range 31.7 |
| Mipomersen | Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 69 mg/dL | Inter-Quartile Range 32.4 |
Primary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point
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.
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).
Population: The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point | -3.4 percentage of baseline | Inter-Quartile Range 24.22 |
| Mipomersen | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point | -40.2 percentage of baseline | Inter-Quartile Range 26.85 |
Comparison: Based upon prior clinical study experience with mipomersen, it was estimated that the standard deviation of the percent change in LDL-C is approximately 22%. With at least 20 patients in the control group and 40 patients in the mipomersen-treated group, this study would have at least 90% power to detect a 20% difference between the 2 groups.p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Apolipoprotein B at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Baseline | 106 mg/dL | Inter-Quartile Range 30.1 |
| Placebo | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 108 mg/dL | Inter-Quartile Range 27.2 |
| Mipomersen | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Baseline | 114 mg/dL | Inter-Quartile Range 25.2 |
| Mipomersen | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 64 mg/dL | Inter-Quartile Range 30.7 |
Secondary
Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 144 mg/dL | Inter-Quartile Range 44.4 |
| Placebo | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 140 mg/dL | Inter-Quartile Range 38.7 |
| Mipomersen | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 144 mg/dL | Inter-Quartile Range 35.1 |
| Mipomersen | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 90 mg/dL | Inter-Quartile Range 38.3 |
Secondary
Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point | -1.7 percentage of baseline | Inter-Quartile Range 18.09 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point | -40.6 percentage of baseline | Inter-Quartile Range 23.59 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | -1.2 percentage of baseline | Inter-Quartile Range 20.43 |
| Mipomersen | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | -38.7 percentage of baseline | Inter-Quartile Range 23.75 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point | -2.7 percentage of baseline | Standard Deviation 14.58 |
| Mipomersen | Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point | -26.4 percentage of baseline | Standard Deviation 18.65 |
p-value: <0.001t-test, 2 sided
Secondary
Total Cholesterol at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 200.0 mg/dL | Standard Deviation 42.1 |
| Placebo | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 192.2 mg/dL | Standard Deviation 38.3 |
| Mipomersen | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 202.6 mg/dL | Standard Deviation 36.8 |
| Mipomersen | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 147.4 mg/dL | Standard Deviation 39.9 |
Other Pre-specified
Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Baseline | 150.8 mg/dL | Standard Deviation 30.5 |
| Placebo | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 147.8 mg/dL | Standard Deviation 27.3 |
| Mipomersen | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Baseline | 156.8 mg/dL | Standard Deviation 25.4 |
| Mipomersen | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 146.8 mg/dL | Standard Deviation 24.5 |
Other Pre-specified
High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 48.4 mg/dL | Standard Deviation 15.9 |
| Placebo | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 48.9 mg/dL | Standard Deviation 16.1 |
| Mipomersen | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 50.8 mg/dL | Standard Deviation 12 |
| Mipomersen | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 51.1 mg/dL | Standard Deviation 12.3 |
Other Pre-specified
Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Baseline | 51.1 mg/dL | Standard Deviation 48.6 |
| Placebo | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 49.5 mg/dL | Standard Deviation 47.3 |
| Mipomersen | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Baseline | 54.3 mg/dL | Standard Deviation 57 |
| Mipomersen | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 39.6 mg/dL | Standard Deviation 47 |
Other Pre-specified
Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point | -1.0 percentage of baseline | Standard Deviation 11.16 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point | -5.6 percentage of baseline | Standard Deviation 12.56 |
p-value: 0.032t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point | 2.2 percentage of baseline | Standard Deviation 16.44 |
| Mipomersen | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point | 2.2 percentage of baseline | Standard Deviation 17.99 |
p-value: 0.977t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point | 2.3 percentage of baseline | Standard Deviation 28.09 |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point | -24.0 percentage of baseline | Standard Deviation 24.47 |
p-value: <0.001t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point | -5.3 percentage of baseline | Standard Deviation 25.31 |
| Mipomersen | Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point | -37.4 percentage of baseline | Standard Deviation 27.24 |
p-value: <0.001t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point | 2.7 percentage of baseline | Inter-Quartile Range 53.26 |
| Mipomersen | Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point | -26.2 percentage of baseline | Inter-Quartile Range 29.21 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
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.
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).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | 1.9 percentage of baseline | Inter-Quartile Range 53.83 |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | -26.7 percentage of baseline | Inter-Quartile Range 28.75 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 2.82 ratio | Standard Deviation 1.383 |
| Placebo | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 2.54 ratio | Standard Deviation 1.147 |
| Mipomersen | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 2.54 ratio | Standard Deviation 0.854 |
| Mipomersen | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 1.54 ratio | Standard Deviation 0.761 |
Other Pre-specified
Triglycerides at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Triglycerides at Baseline and at the Primary Efficacy Time Point | Baseline | 139 mg/dL | Inter-Quartile Range 66.1 |
| Placebo | Triglycerides at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 135 mg/dL | Inter-Quartile Range 97.5 |
| Mipomersen | Triglycerides at Baseline and at the Primary Efficacy Time Point | Baseline | 143 mg/dL | Inter-Quartile Range 65.3 |
| Mipomersen | Triglycerides at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 88 mg/dL | Inter-Quartile Range 55.7 |
Other Pre-specified
Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
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).
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 28 mg/dL | Inter-Quartile Range 13.2 |
| Placebo | Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 27 mg/dL | Inter-Quartile Range 16.3 |
| Mipomersen | Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 29 mg/dL | Inter-Quartile Range 12.1 |
| Mipomersen | Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 18 mg/dL | Inter-Quartile Range 11.1 |