Congenital Abnormalities, Dyslipidemias, Genetic Diseases, Inborn, Hypercholesterolemia, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Hyperlipoproteinemias, Hyperlipoproteinemia Type II, Infant, Newborn, Diseases, Lipid Metabolism Disorders, Lipid Metabolism, Inborn Errors, Metabolic Diseases, Metabolic Disorder, Metabolism, Inborn Errors
Conditions
Keywords
Familial Hypercholesterolemia, FH, Heterozygous Familial Hypercholesterolemia, HeFH, Homozygous Familial Hypercholesterolemia, HoFH
Brief summary
To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in participants with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who had completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108 (NCT00794664) clinical drug trials.
Detailed description
All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed \<50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.
Interventions
Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.
Sponsors
Ionis Pharmaceuticals, Inc.
Kastle Therapeutics, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 \[NCT00607373\], 301012-CS7 \[NCT00706849\], 301012-CS17 \[NCT00477594\], or MIPO3500108 \[NCT00794664\])
Exclusion criteria
* Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Apolipoprotein B (Apo B) | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Total Cholesterol | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LDL Particles' Size (Medium) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in LDL Particles' Size (Small) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in LDL Particles' Size (Very Small) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in HDL Particles' Size (Large) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in HDL Particles' Size (Medium) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in HDL Particles' Size (Small) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Triglycerides | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in VLDL Particles' Size (Medium) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in VLDL Particles' Size (Small) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Change From Baseline in C-Reactive Protein | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Apolipoprotein A-1 | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in Lipoprotein (a) | Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in LDL Particles' Size (Total) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
| Percent Change From Baseline in LDL Particles' Size (Large) | Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) | Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study). |
Countries
Brazil, Canada, Singapore, South Africa, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 33 centers in 7 countries. A total of 144 patients were enrolled in the study. 1 patient never received study drug. 2 of the enrolled patients came from a phase 2 study and its extension and consequently had very different treatment from the other treated patients, and thus were excluded from all summary tables.
Pre-assignment details
Participants who successfully completed ISIS 301012 CS5 (NCT00607373), ISIS 301012CS7 (NCT00706849), ISIS 301012CS17 (NCT00694109) or MIPO3500108 (NCT00794664) with an acceptable safety profile were eligible for study.
Participants by arm
| Arm | Count |
|---|---|
| Mipomersen Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed \<50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment. | 141 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 74 |
| Overall Study | Consented but no additional treatment | 3 |
| Overall Study | Enrolled but not treated | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Not consent of more 2 years of treatment | 18 |
| Overall Study | Other | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Mipomersen |
|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 15.3 |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 141 / 141 |
| serious Total, serious adverse events | 36 / 141 |
Outcome results
Primary
Percent Change From Baseline in Apolipoprotein B (Apo B)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 26 (n = 130) | -28.9 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 52 (n = 111) | -28.1 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 76 (n = 66) | -30.3 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 104 (n = 57) | -31.2 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 130 (n = 43) | -29.1 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 156 (n = 30) | -30.2 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 182 (n = 26) | -31.1 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 208 (n = 27) | -33.3 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | week 234 (n = 17) | -31.4 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein B (Apo B) | 24 weeks post last dose (n=117) | -3.46 percent change |
Primary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 26 (n = 130) | -28.5 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 52 (n = 111) | -27 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 76 (n = 66) | -27.3 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 104 (n = 57) | -27.9 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 130 (n = 42) | -21.9 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 156 (n = 30) | -21.4 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 182 (n = 26) | -23.6 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 208 (n = 27) | -26.3 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | week 234 (n = 17) | -22.5 percent change |
| Mipomersen | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | 24 weeks post last dose (n=117) | 1.6 percent change |
Primary
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 26 (n = 130) | -27.2 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 52 (n = 111) | -25.4 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 76 (n = 66) | -25 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 104 (n = 57) | -26.2 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 130 (n = 43) | -20.7 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 156 (n = 30) | -20 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 182 (n = 26) | -21.7 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 208 (n = 27) | -23.9 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | week 234 (n = 17) | -19.9 percent change |
| Mipomersen | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) | 24 weeks post last dose (n=117) | 2.5 percent change |
Primary
Percent Change From Baseline in Total Cholesterol
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 26 (n = 130) | -21.7 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 52 (n = 111) | -20.4 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 76 (n = 66) | -20.1 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 104 (n = 57) | -19.8 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 130 (n = 43) | -14.9 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 156 (n = 30) | -14.4 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 182 (n = 26) | -14.3 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 208 (n = 27) | -16.5 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | week 234 (n = 17) | -12.5 percent change |
| Mipomersen | Percent Change From Baseline in Total Cholesterol | 24 weeks post last dose (n=117) | 1.94 percent change |
Secondary
Change From Baseline in C-Reactive Protein
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Change From Baseline in C-Reactive Protein | week 26 (n=130) | 0.67 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 52 (n=111) | -0.37 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 76 (n=84) | -1.05 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 104 (n=58) | 0.12 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 130 (n=42) | -0.18 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 156 (n=30) | 0.02 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 182 (n=31) | 0.73 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 208 (n=27) | 0.2 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | week 234 (n=18) | 0.53 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | End of treatment (n=140) | 0.41 percent change |
| Mipomersen | Change From Baseline in C-Reactive Protein | 24 weeks post last dose (n=116) | 0.09 percent change |
Secondary
Percent Change From Baseline in Apolipoprotein A-1
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 26 (n=130) | -1.01 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 52 (n=111) | -1.59 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 76 (n=66) | -3.73 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 104 (n=57) | -4.33 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 130 (n=43) | -1.37 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 156 (n=30) | -5.55 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 182 (n=26) | -3.17 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 208 (n=27) | -2.19 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | week 234 (n=17) | 3.68 percent change |
| Mipomersen | Percent Change From Baseline in Apolipoprotein A-1 | 24 weeks post last dose (n = 117) | -0.67 percent change |
Secondary
Percent Change From Baseline in HDL Particles' Size (Large)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Large).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | week 52 (n = 89) | 160.8 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | week 104 (n = 47) | 43.23 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | week 156 (n = 20) | 58.26 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | week 208 (n = 19) | 61.76 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | End of treatment (n=134) | 121.16 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Large) | 24 weeks post last dose (n=110) | 85.93 percent change |
Secondary
Percent Change From Baseline in HDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for HDL Particles' Size (Medium).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | week 52 (n = 44) | 154.77 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | week 104 (n = 28) | 176.14 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | week 156 (n = 9) | 21.24 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | week 208 (n = 8) | 838.32 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | End of treatment (n= 68) | 388.16 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Medium) | 24 weeks post last dose (n=56) | 233.78 percent change |
Secondary
Percent Change From Baseline in HDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for HDL Particles' Size (Small).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | 24 weeks post last dose (n=115) | 8.31 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | week 52 (n = 91) | 1.83 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | week 104 (n = 47) | -9.81 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | week 156 (n = 20) | -14.18 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | week 208 (n = 19) | -11.47 percent change |
| Mipomersen | Percent Change From Baseline in HDL Particles' Size (Small) | End of treatment (n= 139) | 0.44 percent change |
Secondary
Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Intermediate Density Lipoprotein Particles' Size.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | week 52 (n = 79) | -9.9 percent change |
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | week 104 (n = 40) | -27.35 percent change |
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | week 156 (n = 16) | 155.42 percent change |
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | week 208 (n = 15) | 32.88 percent change |
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | End of treatment (n= 122) | 24.66 percent change |
| Mipomersen | Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size | 24 weeks post last dose (n=101) | 57.46 percent change |
Secondary
Percent Change From Baseline in LDL Particles' Size (Large)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Large).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | week 52 (n = 91) | -5.01 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | week 104 (n = 47) | -14.32 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | week 156 (n = 20) | -27.04 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | week 208 (n = 19) | -22.67 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | End of treatment (n=139) | -2.94 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Large) | 24 weeks post last dose (n=115) | 6.19 percent change |
Secondary
Percent Change From Baseline in LDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Medium).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | week 52 (n = 91) | -9.50 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | week 104 (n = 47) | 11.09 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | week 156 (n = 20) | -19.62 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | week 208 (n = 19) | -15.82 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | End of treatment (n=139) | -5.65 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Medium) | 24 weeks post last dose (n=115) | 46.92 percent change |
Secondary
Percent Change From Baseline in LDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Small).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | week 52 (n = 91) | -8.79 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | week 104 (n = 47) | 1.72 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | week 156 (n = 20) | -18.95 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | week 208 (n = 19) | -27.95 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | End of treatment (n=139) | -5.17 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Small) | 24 weeks post last dose (n=115) | 51.94 percent change |
Secondary
Percent Change From Baseline in LDL Particles' Size (Total)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Total).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | week 52 (n = 91) | -26.77 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | week 104 (n = 47) | -27.77 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | week 156 (n = 20) | -25.1 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | week 208 (n = 19) | -32.65 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | End of treatment (n=139) | -22.63 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Total) | 24 weeks post last dose (n=115) | 6.11 percent change |
Secondary
Percent Change From Baseline in LDL Particles' Size (Very Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Very Small).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | week 52 (n = 91) | -5.05 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | week 104 (n = 47) | -0.11 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | week 156 (n = 20) | -18.7 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | week 208 (n = 19) | -30.77 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | End of treatment (n=139) | 0.75 percent change |
| Mipomersen | Percent Change From Baseline in LDL Particles' Size (Very Small) | 24 weeks post last dose (n=115) | 60.22 percent change |
Secondary
Percent Change From Baseline in Lipoprotein (a)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 26 (n = 130) | -20.5 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 52 (n = 111) | -19 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 76 (n = 66) | -17.9 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 104 (n = 57) | -16.6 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 130 (n = 43) | -15.8 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 156 (n = 30) | -9.1 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 182 (n = 26) | -9 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 208 (n = 27) | -9.9 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | week 234 (n = 17) | -18.3 percent change |
| Mipomersen | Percent Change From Baseline in Lipoprotein (a) | 24 weeks post last dose (n=117) | 0 percent change |
Secondary
Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Total VLDL Particles' Size and Chylomicron Particles' Size.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | week 52 (n = 91) | 19.94 percent change |
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | week 104 (n = 47) | -14.25 percent change |
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | week 156 (n = 20) | 3.48 percent change |
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | week 208 (n = 19) | -18.66 percent change |
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | End of treatment (n= 139) | 12.82 percent change |
| Mipomersen | Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size | 24 weeks post last dose (n=115) | 19.69 percent change |
Secondary
Percent Change From Baseline in Triglycerides
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Triglycerides | week 26 (n = 130) | -20.1 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 52 (n = 111) | -7.9 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 76 (n = 66) | -10.2 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 104 (n = 57) | -12.5 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 130 (n = 43) | -10.9 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 156 (n = 30) | -10.4 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 182 (n = 26) | -12.9 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 208 (n = 27) | -13.9 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | week 234 (n = 17) | 1.3 percent change |
| Mipomersen | Percent Change From Baseline in Triglycerides | 24 weeks post last dose (n=117) | 2.1 percent change |
Secondary
Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | week 52 (n = 86) | 109.23 percent change |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | week 104 (n = 46) | 107.5 percent change |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | week 156 (n = 19) | 123.42 percent change |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | week 208 (n = 18) | 241.76 percent change |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | End of treatment (n= 132) | 86.75 percent change |
| Mipomersen | Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size | 24 weeks post last dose (n=110) | 90.82 percent change |
Secondary
Percent Change From Baseline in VLDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for VLDL Particles' Size (Medium).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | week 52 (n = 88) | 70.81 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | week 104 (n = 47) | 97.74 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | week 156 (n = 20) | 172.46 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | week 208 (n = 19) | 98.7 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | End of treatment (n= 136) | 63.25 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Medium) | 24 weeks post last dose (n=113) | 99.57 percent change |
Secondary
Percent Change From Baseline in VLDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Population: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for VLDL Particles' Size (Small).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | week 52 (n = 91) | 49.51 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | week 104 (n = 47) | 30.48 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | week 156 (n = 20) | 9.34 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | week 208 (n = 19) | -30.36 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | End of treatment (n= 139) | 31.27 percent change |
| Mipomersen | Percent Change From Baseline in VLDL Particles' Size (Small) | 24 weeks post last dose (n=115) | 32.14 percent change |