Atherosclerosis, Hypercholesterolemia, Statin Adverse Reaction
Conditions
Keywords
hyperlididemia, LDL, cholesterol, statin intolerance
Brief summary
The purpose of this study is to determine if bempedoic acid (ETC-1002) added-on to ezetimibe therapy is effective and safe versus placebo in patients with elevated LDL cholesterol.
Interventions
DRUGBempedoic acid
bempedoic acid 180 mg tablet
DRUGEzetimibe
ezetimibe 10 mg tablet
OTHERPlacebo
matching placebo tablet
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-cholesterol greater than or equal to 100 mg/dL at screening * Men and nonpregnant, nonlactating women * Use of stable lipid-modifying therapy for at least 4 weeks prior to screening that includes ezetimibe 10mg daily
Exclusion criteria
* Fasting blood triglycerides greater than or equal to 500 mg/dL * Body Mass Index (BMI) greater than or equal to 50 kg/m2 * Recent history of clinically significant cardiovascular disease * Use of statin therapy where doses are greater than those defined as low-dose within 4 weeks prior to screening; where low-dose is defined as an average daily dose of rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg, or pitavastatin 2 mg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Bempedoic Acid = BA. 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 as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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 was calculated as: (\[TC value at Week 12 minus Baseline value\] 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 as a 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 Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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 was calculated as: (\[non-HDL-C value at Week 12 minus Baseline value\] 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 as a 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 Apolipoprotein B (apoB) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for apoB. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in apoB was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing apoB data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. |
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for hsCRP. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. |
| Percent Change From Baseline to Week 12 in Triglycerides (TGs) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to D 1. Percent change from baseline was calculated as: \[(TGs value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) | Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was 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 was calculated as: \[(HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 16 weeks | TEAEs, defined as an adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and prior to the last dose of double-blind study drug + 30 days, were collected and reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Weeks 4 and 8 in TC | Week 4 and Week 8 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(TC value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Weeks 4 and 8 in TGs | Week 4 and Week 8 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(TGs value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Weeks 4 and 8 in HDL-C | Week 4 and Week 8 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for HDL-C. Baseline was 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 was calculated as: \[(HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate. |
| Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Week 4, Week 8 and Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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. Absolute change from baseline was calculated as: LDL-C value at Week 4, 8, or 12 minus Baseline value. |
| Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C | Week 4 and Week 8 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(Non-HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate. |
| Percent Change From Baseline to Weeks 4 and 8 in LDL-C | Week 4 and Week 8 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(LDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate. |
Countries
United States
Participant flow
Recruitment details
Out of the 269 participants who were randomized to the double-blind treatment period, 181 participants were randomized to bempedoic acid and 88 participants to placebo. One participant in the placebo group was randomized but never started treatment.
Pre-assignment details
The study consisted of an approximate 1-week screening period, a 4-week single-blind placebo and ezetimibe run-in period, and a 12-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablet, once-daily by mouth and ezetimibe 10 mg capsules, once-daily by mouth for 4 weeks prior to the 12-week treatment period. During the treatment period, participants received placebo tablet, once-daily by mouth and ezetimibe 10 mg capsules, once-daily by mouth for 12 weeks. | 88 |
| Bempedoic Acid Participants received placebo tablet, once-daily by mouth and ezetimibe 10 mg capsules, once-daily by mouth for 4 weeks prior to the 12-week treatment period. During the treatment period, participants received bempedoic acid 180 mg tablet, once-daily by mouth and ezetimibe 10 mg capsules, once-daily by mouth for 12 weeks. | 181 |
| Total | 269 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Sponsor decision | 1 | 0 |
| Overall Study | Withdrawal by patient | 2 | 0 |
Baseline characteristics
| Characteristic | Bempedoic Acid | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.77 | 63.7 years STANDARD_DEVIATION 11.32 | 63.8 years STANDARD_DEVIATION 10.93 |
| Apolipoprotein B (apoB) | 123.3 mg/dL STANDARD_DEVIATION 26.48 | 115.8 mg/dL STANDARD_DEVIATION 23.47 | 120.9 mg/dL STANDARD_DEVIATION 25.75 |
| Body mass index (BMI) | 29.52 kilograms per square meter (kg/m2) STANDARD_DEVIATION 4.74 | 30.45 kilograms per square meter (kg/m2) STANDARD_DEVIATION 5.787 | 29.83 kilograms per square meter (kg/m2) STANDARD_DEVIATION 5.114 |
| Concomitant illness: Cardiac disorder Participants with cardiac disorder | 49 Participants | 22 Participants | 71 Participants |
| Concomitant illness: Cardiac disorder Participants without cardiac disorder | 132 Participants | 66 Participants | 198 Participants |
| Concomitant lipid-modifying therapy medications Bile acid sequestrants | 1 Participants | 1 Participants | 2 Participants |
| Concomitant lipid-modifying therapy medications Fibrates | 7 Participants | 3 Participants | 10 Participants |
| Concomitant lipid-modifying therapy medications Nicotinic acid and derivatives | 3 Participants | 4 Participants | 7 Participants |
| Concomitant lipid-modifying therapy medications No concomitant lipid-modifying therapies | 92 Participants | 47 Participants | 139 Participants |
| Concomitant lipid-modifying therapy medications Other lipid-modifying therapies | 19 Participants | 8 Participants | 27 Participants |
| Concomitant lipid-modifying therapy medications Statins | 59 Participants | 25 Participants | 84 Participants |
| Diastolic blood pressure | 76.4 mmHg STANDARD_DEVIATION 8.46 | 77.0 mmHg STANDARD_DEVIATION 7.56 | 76.6 mmHg STANDARD_DEVIATION 8.17 |
| Estimated glomerular filtration rate (eGFR) category <60 mL/min/1.73m2 | 26 Participants | 14 Participants | 40 Participants |
| Estimated glomerular filtration rate (eGFR) category 60 to <90 mL/min/1.73m2 | 110 Participants | 57 Participants | 167 Participants |
| Estimated glomerular filtration rate (eGFR) category ≥90 mL/min/1.73m2 | 45 Participants | 17 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 23 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants | 65 Participants | 203 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| High-density lipoprotein cholesterol (HDL-C) | 55.84 mg/dL STANDARD_DEVIATION 16.326 | 57.07 mg/dL STANDARD_DEVIATION 21.319 | 56.24 mg/dL STANDARD_DEVIATION 18.08 |
| High-sensitivity C-reactive protein (hsCRP) | 2.205 mg/dL | 2.260 mg/dL | 2.215 mg/dL |
| History of diabetes Participants with history of diabetes | 35 Participants | 17 Participants | 52 Participants |
| History of diabetes Participants without history of diabetes | 146 Participants | 71 Participants | 217 Participants |
| History of hypertension Participants with history of hypertension | 111 Participants | 51 Participants | 162 Participants |
| History of hypertension Participants without history of hypertension | 70 Participants | 37 Participants | 107 Participants |
| LDL-C category <130 mg/dL | 99 Participants | 56 Participants | 155 Participants |
| LDL-C category ≥130 to <160 mg/dL | 53 Participants | 24 Participants | 77 Participants |
| LDL-C category ≥160 mg/dL | 29 Participants | 8 Participants | 37 Participants |
| Low-density lipoprotein cholesterol (LDL-C) | 129.77 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 30.871 | 123.02 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 27.197 | 127.56 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 29.838 |
| Non-high-density lipoprotein cholesterol (non-HDL-C) | 162.41 mg/dL STANDARD_DEVIATION 35.413 | 151.55 mg/dL STANDARD_DEVIATION 32.734 | 158.85 mg/dL STANDARD_DEVIATION 34.874 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 10 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 165 Participants | 75 Participants | 240 Participants |
| Sex: Female, Male Female | 109 Participants | 56 Participants | 165 Participants |
| Sex: Female, Male Male | 72 Participants | 32 Participants | 104 Participants |
| Systolic blood pressure | 127.3 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.34 | 126.0 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.5 | 126.9 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.38 |
| Total cholesterol (TC) | 218.24 mg/dL STANDARD_DEVIATION 35.883 | 208.62 mg/dL STANDARD_DEVIATION 35.712 | 215.09 mg/dL STANDARD_DEVIATION 36.045 |
| Triglycerides (TGs) | 166.93 mg/dL STANDARD_DEVIATION 75.683 | 143.39 mg/dL STANDARD_DEVIATION 61.932 | 159.23 mg/dL STANDARD_DEVIATION 72.213 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 181 |
| other Total, other adverse events | 18 / 87 | 46 / 181 |
| serious Total, serious adverse events | 3 / 87 | 5 / 181 |
Outcome results
Primary
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Bempedoic Acid = BA. 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 as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: 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) | 4.99 percent change | Standard Error 2.299 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) | -23.46 percent change | Standard Error 1.945 |
p-value: <0.00195% CI: [-34.376, -22.531]ANCOVA
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs, defined as an adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and prior to the last dose of double-blind study drug + 30 days, were collected and reported.
Time frame: Up to approximately 16 weeks
Population: Safety Analysis Set: all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group that they actually received, regardless of their randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs | 39 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Non-serious TEAEs | 18 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 3 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Bempedoic Acid | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Bempedoic Acid | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs | 88 Participants |
| Bempedoic Acid | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 5 Participants |
| Bempedoic Acid | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Non-serious TEAEs | 46 Participants |
Secondary
Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for apoB. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in apoB was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing apoB data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Time frame: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | 4.74 Percent change | Standard Error 1.786 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | -14.58 Percent change | Standard Error 1.497 |
p-value: <0.00195% CI: [-23.908, -14.732]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was 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 was calculated as: \[(HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate.
Time frame: 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 High-density Lipoprotein Cholesterol (HDL-C) | -1.38 percent change | Standard Error 1.389 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) | -7.27 percent change | Standard Error 1.214 |
p-value: =0.00295% CI: [-9.528, -2.25]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for hsCRP. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: \[(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100.
Time frame: 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) | 2.088 Percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | -32.521 Percent change |
p-value: <0.00195% CI: [-44.761, -17.401]Wilcoxon Rank Sum Test
Secondary
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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 was calculated as: (\[non-HDL-C value at Week 12 minus Baseline value\] 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 as a 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: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | 5.19 percent change | Standard Error 2.202 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -18.38 percent change | Standard Error 1.668 |
p-value: <0.00195% CI: [-29.005, -18.121]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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 was calculated as: (\[TC value at Week 12 minus Baseline value\] 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 as a 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: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | 2.88 Percent change | Standard Error 1.553 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -15.11 Percent change | Standard Error 1.282 |
p-value: <0.00195% CI: [-21.94, -14.03]ANCOVA
Secondary
Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to D 1. Percent change from baseline was calculated as: \[(TGs value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
Time frame: 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) | 9.23 Percent change | Standard Error 4.218 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Triglycerides (TGs) | 4.70 Percent change | Standard Error 3.068 |
p-value: =0.38895% CI: [-14.877, 5.812]ANCOVA
Other Pre-specified
Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for 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. Absolute change from baseline was calculated as: LDL-C value at Week 4, 8, or 12 minus Baseline value.
Time frame: Week 4, Week 8 and Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 4 | 3.6 milligrams per deciliter (mg/dL) | Standard Deviation 15.65 |
| Placebo | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 8 | 3.9 milligrams per deciliter (mg/dL) | Standard Deviation 19.22 |
| Placebo | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 12 | 5.3 milligrams per deciliter (mg/dL) | Standard Deviation 23.96 |
| Bempedoic Acid | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 4 | -37.4 milligrams per deciliter (mg/dL) | Standard Deviation 30.9 |
| Bempedoic Acid | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 8 | -34.5 milligrams per deciliter (mg/dL) | Standard Deviation 32.29 |
| Bempedoic Acid | Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C | Change from Baseline at Week 12 | -32.9 milligrams per deciliter (mg/dL) | Standard Deviation 34.14 |
Other Pre-specified
Percent Change From Baseline to Weeks 4 and 8 in HDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for HDL-C. Baseline was 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 was calculated as: \[(HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate.
Time frame: Week 4 and Week 8
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in HDL-C | Week 4 | 0.85 Percent change | Standard Error 1.204 |
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in HDL-C | Week 8 | -1.33 Percent change | Standard Error 1.272 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in HDL-C | Week 4 | -7.73 Percent change | Standard Error 1.081 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in HDL-C | Week 8 | -7.75 Percent change | Standard Error 1.144 |
Comparison: Change from Baseline to Week 4p-value: <0.00195% CI: [-11.778, -5.394]ANCOVA
Comparison: Change from Baseline to Week 8p-value: <0.00195% CI: [-9.798, -3.049]ANCOVA
Other Pre-specified
Percent Change From Baseline to Weeks 4 and 8 in LDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(LDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate.
Time frame: Week 4 and Week 8
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in LDL-C | Week 4 | 3.05 Percent change | Standard Error 1.442 |
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in LDL-C | Week 8 | 3.61 Percent change | Standard Error 1.773 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in LDL-C | Week 4 | -28.04 Percent change | Standard Error 1.704 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in LDL-C | Week 8 | -25.51 Percent change | Standard Error 1.773 |
Comparison: Change from Baseline to Week 4p-value: <0.00195% CI: [-35.498, -26.682]ANCOVA
Comparison: Change from Baseline to Week 8p-value: <0.00195% CI: [-34.074, -24.168]ANCOVA
Other Pre-specified
Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(Non-HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate.
Time frame: Week 4 and Week 8
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C | Week 4 | 3.08 Percent change | Standard Error 1.362 |
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C | Week 8 | 3.71 Percent change | Standard Error 1.66 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C | Week 4 | -22.17 Percent change | Standard Error 1.457 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C | Week 8 | -20.04 Percent change | Standard Error 1.531 |
Comparison: Change from Baseline to Week 4p-value: <0.00195% CI: [-29.204, -21.308]ANCOVA
Comparison: Change from Baseline to Week 8p-value: <0.00195% CI: [-28.219, -19.276]ANCOVA
Other Pre-specified
Percent Change From Baseline to Weeks 4 and 8 in TC
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: \[(TC value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] 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 as a fixed effects and Baseline as a covariate.
Time frame: Week 4 and Week 8
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in TC | Week 4 | 2.08 Percent change | Standard Error 1 |
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in TC | Week 8 | 1.82 Percent change | Standard Error 1.11 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in TC | Week 4 | -18.33 Percent change | Standard Error 1.129 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in TC | Week 8 | -16.63 Percent change | Standard Error 1.215 |
Comparison: Change from Baseline to Week 4p-value: <0.00195% CI: [-23.39, -17.43]ANCOVA
Comparison: Change from Baseline to Week 8p-value: <0.00195% CI: [-21.71, -15.206]ANCOVA
Other Pre-specified
Percent Change From Baseline to Weeks 4 and 8 in TGs
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: \[(TGs value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
Time frame: Week 4 and Week 8
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in TGs | Week 4 | 6.00 Percent change | Standard Error 4.273 |
| Placebo | Percent Change From Baseline to Weeks 4 and 8 in TGs | Week 8 | 7.68 Percent change | Standard Error 4.246 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in TGs | Week 4 | 5.20 Percent change | Standard Error 2.536 |
| Bempedoic Acid | Percent Change From Baseline to Weeks 4 and 8 in TGs | Week 8 | 7.60 Percent change | Standard Error 2.849 |
Comparison: Change from Baseline to Week 4p-value: =0.87395% CI: [-10.663, 9.059]ANCOVA
Comparison: Change from Baseline to Week 8p-value: =0.98895% CI: [-10.215, 10.055]ANCOVA