Atherosclerotic Cardiovascular Disease, Hypercholesterolemia
Conditions
Keywords
hyperlipidemia, cholesterol, familial hypercholesterolemia, atherosclerotic cardiovascular disease, ASCVD, HeFH, LDL
Brief summary
The purpose of this study is to see if bemedoic acid (ETC-1002) is effective versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol not adequately controlled by their current therapy.
Interventions
DRUGbempedoic acid
bempedoic acid 180 mg tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
DRUGplacebo
Matching placebo tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
Sponsors
Esperion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fasting LDL-C ≥100 mg/dL * High cardiovascular risk (diagnosis of HeFH and/or ASCVD) * Be on maximally tolerated lipid-modifying therapy (LMT), including maximally tolerated statin either alone or in combination with other LMTs
Exclusion criteria
* Total fasting triglyceride ≥500 mg/dL * Renal dysfunction or nephrotic syndrome or history of nephritis * Body Mass Index (BMI) ≥50kg/m2 * Significant cardiovascular disease or cardiovascular event in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline; Week 12 | Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (atherosclerotic cardiovascular diseases \[ASCVD\] and heterozygous familial hypercholesterolemia \[HeFH\]) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 are imputed using multiple imputation method taking into account adherence to treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline; Week 12 | Baseline is defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing non-HDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. |
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Baseline; Week 12 | Baseline is defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing TC data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. |
| Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B) | Baseline; Week 12 | Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing apo B data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. |
| Percent Change From Baseline to Week 24 in LDL-C | Baseline; Week 24 | Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 24 were imputed using multiple imputation method taking into account adherence to treatment. |
| Change From Baseline to Week 12 in LDL-C | Baseline; Week 12 | Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data. |
| Change From Baseline to Week 24 in LDL-C | Baseline; Week 24 | Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data. |
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | Baseline; Week 12 | Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 52 in Apo B | Baseline; Week 52 | Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 24 in hsCRP | Baseline; Week 24 | Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. |
| Percent Change From Baseline to Week 12 in Triglycerides (TGs) | Baseline; Week 12 | Baseline is defined as the mean of the TG values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TG was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Change From Baseline to Week 52 in LDL-C | Baseline; Week 52 | Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data. Change from Baseline in LDL-C was analyzed using an ANCOVA model with change from baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and baseline as a covariate. |
| Percent Change From Baseline to Week 52 in hsCRP | Baseline; Week 52 | Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. |
| Percent Change From Baseline to Week 12 in HDL-C | Baseline; Week 12 | Baseline is defined as the mean of the HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 52 in LDL-C | Baseline; Week 52 | Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 24 in Non-HDL-C | Baseline; Week 24 | Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 52 in Non-HDL-C | Baseline; Week 52 | Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 24 in TC | Baseline; Week 24 | Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 52 in TC | Baseline; Week 52 | Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 24 in Apo B | Baseline; Week 24 | Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. |
Countries
United States
Participant flow
Recruitment details
A total of 779 participants were randomized 2:1 to receive either bempedoic acid or placebo.
Pre-assignment details
The study consisted of 3 periods: a 1-week screening period; a 4-week single-blind, placebo run-in period; and a 52-week double-blind, randomized treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received placebo once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study. | 257 |
| Bempedoic Acid Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received a bempedoic acid 180 milligram (mg) tablet once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study. | 522 |
| Total | 779 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Could not attend study visits | 0 | 1 |
| Overall Study | Death | 3 | 8 |
| Overall Study | Lost to Follow-up | 1 | 9 |
| Overall Study | Moved out of the country | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 7 |
Baseline characteristics
| Characteristic | Placebo | Bempedoic Acid | Total |
|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 8.73 | 64.1 years STANDARD_DEVIATION 8.82 | 64.3 years STANDARD_DEVIATION 8.79 |
| Background LMT No LMT or statin | 14 Participants | 30 Participants | 44 Participants |
| Background LMT Other LMTs without statins | 15 Participants | 22 Participants | 37 Participants |
| Background LMT Statins with or without other LMTs | 228 Participants | 470 Participants | 698 Participants |
| Background LMT Statins with other LMTs | 32 Participants | 54 Participants | 86 Participants |
| Background LMT Statins without other LMTs | 196 Participants | 416 Participants | 612 Participants |
| Body mass index (BMI) | 30.64 kilograms per meters squared (kg/m^2) STANDARD_DEVIATION 5.048 | 30.01 kilograms per meters squared (kg/m^2) STANDARD_DEVIATION 5.192 | 30.22 kilograms per meters squared (kg/m^2) STANDARD_DEVIATION 5.15 |
| Concomitant lipid-modifying therapy (LMT) medications Bile acid sequestrants | 3 Participants | 5 Participants | 8 Participants |
| Concomitant lipid-modifying therapy (LMT) medications Fibrates | 17 Participants | 26 Participants | 43 Participants |
| Concomitant lipid-modifying therapy (LMT) medications Nicotinic acid and derivatives | 0 Participants | 1 Participants | 1 Participants |
| Concomitant lipid-modifying therapy (LMT) medications Other lipidmodifying therapies | 38 Participants | 63 Participants | 101 Participants |
| Concomitant lipid-modifying therapy (LMT) medications Statins | 232 Participants | 478 Participants | 710 Participants |
| Disease history Coronary heart disease | 205 Participants | 432 Participants | 637 Participants |
| Disease history Diabetes | 81 Participants | 155 Participants | 236 Participants |
| Disease history Hypertension | 224 Participants | 438 Participants | 662 Participants |
| Disease history Impaired fasting glucose | 5 Participants | 9 Participants | 14 Participants |
| Estimated glomerular filtration rate (eGFR) category <60 mL/min/1.73 m^2 | 37 Participants | 77 Participants | 114 Participants |
| Estimated glomerular filtration rate (eGFR) category ≥60 to <90 mL/min/1.73 m^2 | 164 Participants | 338 Participants | 502 Participants |
| Estimated glomerular filtration rate (eGFR) category ≥90 mL/min/1.73 m^2 | 56 Participants | 107 Participants | 163 Participants |
| History of atherosclerotic cardiovascular disease (ASCVD) | 241 Participants | 495 Participants | 736 Participants |
| History of HeFH | 16 Participants | 27 Participants | 43 Participants |
| History of impaired fasting glucose | 5 Participants | 9 Participants | 14 Participants |
| LDL-C category ≥130 and <160 mg/dL | 45 Participants | 89 Participants | 134 Participants |
| LDL-C category <130 mg/dL | 173 Participants | 365 Participants | 538 Participants |
| LDL-C category ≥160 mg/dL | 39 Participants | 68 Participants | 107 Participants |
| Mean apolipoprotein B (apoB) | 118.6 mg/dL STANDARD_DEVIATION 30.53 | 116.2 mg/dL STANDARD_DEVIATION 29.58 | 117.0 mg/dL STANDARD_DEVIATION 29.9 |
| Mean low-density lipoprotein cholesterol (LDL-C) | 122.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 38.3 | 119.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 37.75 | 120.43 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 37.931 |
| Mean non-high-density lipoprotein cholesterol (non-HDL-C) | 153.7 mg/dL STANDARD_DEVIATION 44.36 | 150.7 mg/dL STANDARD_DEVIATION 42.75 | 151.7 mg/dL STANDARD_DEVIATION 43.28 |
| Mean total cholesterol (TC) | 204.8 mg/dL STANDARD_DEVIATION 46.06 | 202.1 mg/dL STANDARD_DEVIATION 42.71 | 203.0 mg/dL STANDARD_DEVIATION 43.83 |
| Median high-sensitivity C-reactive protein (hsCRP) | 1.880 milligrams per Liter | 1.610 milligrams per Liter | 1.700 milligrams per Liter |
| Median triglycerides | 143.00 mg/dL | 139.25 mg/dL | 140.00 mg/dL |
| Numer of participants receiving ezetimibe | 24 Participants | 39 Participants | 63 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 24 Participants | 36 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 244 Participants | 491 Participants | 735 Participants |
| Sex: Female, Male Female | 89 Participants | 194 Participants | 283 Participants |
| Sex: Female, Male Male | 168 Participants | 328 Participants | 496 Participants |
| Statin intensity High intensity | 135 Participants | 278 Participants | 413 Participants |
| Statin intensity Low intensity or no statin | 40 Participants | 78 Participants | 118 Participants |
| Statin intensity Moderate intensity | 82 Participants | 166 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 257 | 6 / 522 |
| other Total, other adverse events | 88 / 257 | 211 / 522 |
| serious Total, serious adverse events | 48 / 257 | 106 / 522 |
Outcome results
Primary
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (atherosclerotic cardiovascular diseases \[ASCVD\] and heterozygous familial hypercholesterolemia \[HeFH\]) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 are imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Baseline; Week 12
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | 2.35 percent change | Standard Error 1.446 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | -15.07 percent change | Standard Error 1.073 |
p-value: <0.00195% CI: [-20.951, -13.896]ANCOVA
Secondary
Change From Baseline to Week 12 in LDL-C
Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in LDL-C | 0.0 mg/dL | Standard Deviation 30.62 |
| Bempedoic Acid | Change From Baseline to Week 12 in LDL-C | -21.2 mg/dL | Standard Deviation 30.82 |
Secondary
Change From Baseline to Week 24 in LDL-C
Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in LDL-C | -1.0 mg/dL | Standard Deviation 37.51 |
| Bempedoic Acid | Change From Baseline to Week 24 in LDL-C | -18.7 mg/dL | Standard Deviation 35.76 |
Secondary
Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B)
Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing apo B data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Baseline; Week 12
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B) | 3.73 percent change | Standard Error 1.34 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B) | -9.29 percent change | Standard Error 0.851 |
p-value: <0.00195% CI: [-16.13, -9.907]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | -9.366 percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | -18.699 percent change |
p-value: <0.03995% CI: [-17.238, -0.434]Wilcoxon Rank Sum Test
Secondary
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Baseline is defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing non-HDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Baseline; Week 12
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | 2.28 percent change | Standard Error 1.351 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -10.75 percent change | Standard Error 0.952 |
p-value: <0.00195% CI: [-16.27, -9.794]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Baseline is defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing TC data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Baseline; Week 12
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | 1.26 percent change | Standard Error 1.01 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -9.94 percent change | Standard Error 0.688 |
p-value: <0.00195% CI: [-13.599, -8.801]ANCOVA
Secondary
Percent Change From Baseline to Week 24 in LDL-C
Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 24 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Baseline; Week 24
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in LDL-C | 2.66 percent change | Standard Error 1.91 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in LDL-C | -12.10 percent change | Standard Error 1.479 |
p-value: <0.00195% CI: [-19.504, -10.027]ANCOVA
Other Pre-specified
Change From Baseline to Week 52 in LDL-C
Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data. Change from Baseline in LDL-C was analyzed using an ANCOVA model with change from baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and baseline as a covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in LDL-C | -4.71 mg/dL | Standard Error 2.216 |
| Bempedoic Acid | Change From Baseline to Week 52 in LDL-C | -19.78 mg/dL | Standard Error 1.433 |
p-value: <0.00195% CI: [-20.26, -9.878]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 12 in HDL-C
Baseline is defined as the mean of the HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in HDL-C | -0.25 percent change | Standard Error 0.864 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in HDL-C | -6.38 percent change | Standard Error 0.741 |
p-value: <0.00195% CI: [-8.369, -3.896]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Baseline is defined as the mean of the TG values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TG was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Triglycerides (TGs) | 6.12 percent change | Standard Error 2.294 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Triglycerides (TGs) | 11.01 percent change | Standard Error 2.312 |
p-value: 0.13495% CI: [-1.504, 11.292]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 24 in Apo B
Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Apo B | 4.39 percent change | Standard Error 2.09 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in Apo B | -8.61 percent change | Standard Error 1.267 |
p-value: <0.00195% CI: [-17.829, -8.175]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 24 in hsCRP
Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in hsCRP | 1.563 percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in hsCRP | -24.107 percent change |
p-value: <0.00195% CI: [-32.25, -10.034]Wilcoxon Rank Sum Test
Other Pre-specified
Percent Change From Baseline to Week 24 in Non-HDL-C
Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Non-HDL-C | 2.44 percent change | Standard Error 1.611 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in Non-HDL-C | -10.19 percent change | Standard Error 1.2 |
p-value: <0.00195% CI: [-16.58, -8.682]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 24 in TC
Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in TC | 1.52 percent change | Standard Error 1.216 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in TC | -9.25 percent change | Standard Error 0.857 |
p-value: <0.00195% CI: [-13.698, -7.848]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 52 in Apo B
Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Apo B | 3.01 percent change | Standard Error 1.502 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in Apo B | -6.56 percent change | Standard Error 0.983 |
p-value: <0.00195% CI: [-13.107, -6.047]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 52 in hsCRP
Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in hsCRP | -6.250 percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in hsCRP | -16.727 percent change |
p-value: 0.10295% CI: [-16.978, 1.653]Wilcoxon Rank Sum Test
Other Pre-specified
Percent Change From Baseline to Week 52 in LDL-C
Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in LDL-C | -0.97 percent change | Standard Error 1.83 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in LDL-C | -13.24 percent change | Standard Error 1.412 |
p-value: <0.00195% CI: [-16.813, -7.722]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 52 in Non-HDL-C
Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Non-HDL-C | -0.42 percent change | Standard Error 1.605 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in Non-HDL-C | -10.34 percent change | Standard Error 1.15 |
p-value: <0.00195% CI: [-13.803, -6.037]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 52 in TC
Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in TC | -1.89 percent change | Standard Error 1.199 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in TC | -10.25 percent change | Standard Error 0.828 |
p-value: <0.00195% CI: [-11.223, -5.493]ANCOVA