Coronary Artery Disease, Heterozygous Familial Hypercholesterolemia
Conditions
Keywords
familial hypercholesterolemia
Brief summary
The purpose of this study is to determine whether mipomersen safely and effectively lowers low-density lipoprotein cholesterol (LDL-C) in patients with Heterozygous Familial Hypercholesterolemia (HeFH) and coronary artery disease (CAD) who are already on a stable dose of other lipid-lowering agents (including maximally tolerated statin therapy).
Detailed description
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated LDL-C, premature onset of atherosclerosis and development of xanthomata. Patients with heterozygous familial hypercholesterolemia typically have total plasma cholesterol between 350 to 550 mg/dL and disease onset in their third and fourth decade. Mipomersen (ISIS 301012) 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 (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. This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period (with the exception of patients who enrolled in the open-label extension study \[Study 301012-CS6; NCT00694109\]). The treatment period spanned the time during which the study treatment was administered until the later of the primary efficacy time point (PET) or 14 days beyond the last day of study drug administration. The post-treatment follow-up period began the day after completion of the treatment period and ended on the day of the patient's last contact date within the study. Following treatment and Week 28 evaluations, eligible patients who tolerated study drug could elect to enroll in an open-label extension study (301012-CS6). Patients who were not eligible for or who elected not to enroll in the open-label extension study and patients who discontinued during the 26-week treatment period were followed in this study for an additional 24 weeks from administration of the last dose of study drug.
Interventions
200 mg /mL
DRUGplacebo
1 mL matching placebo
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 Heterozygous Familial Hypercholesterolemia (HeFH) * Diagnosis of Coronary Artery Disease (CAD) * Stable lipid-lowering therapy for 12 weeks * On maximally tolerated statin therapy with at least 1 statin at a dose greater than zero, per Investigator judgment * Stable low-fat diet for 8 weeks * Stable weight for 6 weeks
Exclusion criteria
* Significant health problems in recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, orthostatic hypotension, uncontrolled hypertension, blood disorders, liver disease, cancer, or digestive problems * Receiving apheresis treatment or last apheresis treatment within 8 weeks
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. 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. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment. |
| LDL 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. |
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 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. |
| 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 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. |
| 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 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). | 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. |
| 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 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 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 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. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Two hundred and twenty-five patients were screened and 124 participants were randomized on Day 1 in a 2:1 ratio to receive mipomersen or placebo once a week for 26 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a placebo subcutaneous injection once a week for 26 weeks. | 41 |
| Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. | 83 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Protocol non-compliance | 0 | 1 |
| Follow-up Period | Withdrawal by Subject | 0 | 2 |
| Treatment Period | Adverse Event | 0 | 9 |
| Treatment Period | Other | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Mipomersen |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 9.3 | 56.1 years STANDARD_DEVIATION 9.5 | 56.2 years STANDARD_DEVIATION 9.7 |
| Alcohol use Current | 31 participants | 95 participants | 64 participants |
| Alcohol use Never | 3 participants | 12 participants | 9 participants |
| Alcohol use Non-current | 7 participants | 17 participants | 10 participants |
| Body Mass Index (BMI) | 30.25 kg/m^2 STANDARD_DEVIATION 3.79 | 29.18 kg/m^2 STANDARD_DEVIATION 4.14 | 28.66 kg/m^2 STANDARD_DEVIATION 4.23 |
| Metabolic syndrome No | 30 participants | 78 participants | 48 participants |
| Metabolic syndrome Yes | 11 participants | 46 participants | 35 participants |
| Race/Ethnicity, Customized Black | 1 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 39 participants | 120 participants | 81 participants |
| Race/Ethnicity, Customized Other race | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized White | 38 participants | 119 participants | 81 participants |
| Sex: Female, Male Female | 13 Participants | 46 Participants | 33 Participants |
| Sex: Female, Male Male | 28 Participants | 78 Participants | 50 Participants |
| Tobacco use Current | 4 participants | 17 participants | 13 participants |
| Tobacco use Never | 20 participants | 58 participants | 38 participants |
| Tobacco use non-current | 17 participants | 49 participants | 32 participants |
| Waist/hip ratio | 0.95 ratio STANDARD_DEVIATION 0.07 | 0.93 ratio STANDARD_DEVIATION 0.08 | 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 | 38 / 41 | 83 / 83 |
| serious Total, serious adverse events | 2 / 41 | 6 / 83 |
Outcome results
Primary
LDL 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 | LDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 142.9 mg/dL | Standard Deviation 51.6 |
| Placebo | LDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 146.4 mg/dL | Standard Deviation 43.4 |
| Mipomersen | LDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 152.9 mg/dL | Standard Deviation 48.7 |
| Mipomersen | LDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 103.9 mg/dL | Standard Deviation 33 |
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. 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. 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 (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point | 5.17 percentage of Baseline | Standard Deviation 18.02 |
| Mipomersen | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point | -28.02 percentage of Baseline | Standard Deviation 26.99 |
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 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 treatment groups.p-value: <0.001t-test, 2 sided
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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Baseline | 126.8 mg/dL | Standard Deviation 33.2 |
| Placebo | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 133.8 mg/dL | Standard Deviation 32.6 |
| Mipomersen | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Baseline | 132.8 mg/dL | Standard Deviation 33.9 |
| Mipomersen | Apolipoprotein B at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 95.0 mg/dL | Standard Deviation 29.7 |
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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 165.3 mg/dL | Standard Deviation 54.5 |
| Placebo | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 168.2 mg/dL | Standard Deviation 47.5 |
| Mipomersen | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 125.2 mg/dL | Standard Deviation 37.8 |
| Mipomersen | Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 175.5 mg/dL | Standard Deviation 51.1 |
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 (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point | 7.02 percentage of baseline | Standard Deviation 16.52 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point | -26.31 percentage of baseline | Standard Deviation 22.16 |
p-value: <0.001t-test, 2 sided
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 (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | 3.74 percentage of baseline | Standard Deviation 16.04 |
| Mipomersen | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | -25.05 percentage of baseline | Standard Deviation 25.71 |
p-value: <0.001t-test, 2 sided
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 | 3.85 percentage of baseline | Standard Deviation 12.84 |
| Mipomersen | Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point | -19.43 percentage of baseline | Standard Deviation 19.25 |
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 | 213.4 mg/dL | Standard Deviation 54.6 |
| Placebo | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 219.0 mg/dL | Standard Deviation 49 |
| Mipomersen | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 225.3 mg/dL | Standard Deviation 51.5 |
| Mipomersen | Total Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 176.0 mg/dL | Standard Deviation 35.9 |
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 | 146.1 mg/dL | Standard Deviation 24.9 |
| Placebo | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 151.5 mg/dL | Standard Deviation 29.1 |
| Mipomersen | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Baseline | 150.7 mg/dL | Standard Deviation 28.1 |
| Mipomersen | Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 145.4 mg/dL | Standard Deviation 27.9 |
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 (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 48 mg/dL | Inter-Quartile Range 11.1 |
| Placebo | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 51 mg/dL | Inter-Quartile Range 13.5 |
| Mipomersen | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 47 mg/dL | Inter-Quartile Range 13.6 |
| Mipomersen | High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 48 mg/dL | Inter-Quartile Range 15.6 |
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 (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Baseline | 53 mg/dL | Inter-Quartile Range 56.2 |
| Placebo | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 51 mg/dL | Inter-Quartile Range 53.5 |
| Mipomersen | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Baseline | 45 mg/dL | Inter-Quartile Range 64.6 |
| Mipomersen | Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 35 mg/dL | Inter-Quartile Range 55.3 |
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 | 3.71 percentage of baseline | Standard Deviation 8.7 |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point | -2.44 percentage of baseline | Standard Deviation 14.22 |
p-value: 0.004t-test, 2 sided
Other Pre-specified
Percent Change From Baseline in High-Density Lipoprotein Cholesterol 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 (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | 5.8 percentage of baseline | Inter-Quartile Range 9.57 |
| Mipomersen | Percent Change From Baseline in High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | 2.5 percentage of baseline | Inter-Quartile Range 18.04 |
p-value: 0.207Wilcoxon (Mann-Whitney)
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 (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point | 0.0 percentage of baseline | Inter-Quartile Range 15.1 |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point | -21.1 percentage of baseline | Inter-Quartile Range 24.22 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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 (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point | -2.8 percentage of baseline | Inter-Quartile Range 19.38 |
| Mipomersen | Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point | -29.2 percentage of baseline | Inter-Quartile Range 29.99 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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 | 0.5 percentage of baseline | Inter-Quartile Range 20.77 |
| Mipomersen | Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point | -14.3 percentage of baseline | Inter-Quartile Range 43.76 |
p-value: 0.042Wilcoxon (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 | 0.0 percentage of baseline | Inter-Quartile Range 20.11 |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point | -13.8 percentage of baseline | Inter-Quartile Range 45.7 |
p-value: 0.023Wilcoxon (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 (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 2.72 ratio | Inter-Quartile Range 1.495 |
| Placebo | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 2.95 ratio | Inter-Quartile Range 1.337 |
| Mipomersen | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Baseline | 2.99 ratio | Inter-Quartile Range 1.353 |
| Mipomersen | Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 2.09 ratio | Inter-Quartile Range 1.034 |
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 | 100 mg/dL | Inter-Quartile Range 53.3 |
| Placebo | Triglycerides at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 101 mg/dL | Inter-Quartile Range 42.5 |
| Mipomersen | Triglycerides at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 89 mg/dL | Inter-Quartile Range 70.1 |
| Mipomersen | Triglycerides at Baseline and at the Primary Efficacy Time Point | Baseline | 107 mg/dL | Inter-Quartile Range 39.6 |
Other Pre-specified
Very Low Density Lipoprotein 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 at Baseline and at the Primary Efficacy Time Point | Baseline | 20 mg/dL | Inter-Quartile Range 9.5 |
| Placebo | Very Low Density Lipoprotein at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 20 mg/dL | Inter-Quartile Range 8.5 |
| Mipomersen | Very Low Density Lipoprotein at Baseline and at the Primary Efficacy Time Point | Baseline | 21 mg/dL | Inter-Quartile Range 7.9 |
| Mipomersen | Very Low Density Lipoprotein at Baseline and at the Primary Efficacy Time Point | Primary efficacy time point | 18 mg/dL | Inter-Quartile Range 14.6 |