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Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk (CLEAR Wisdom)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02991118
Recruitment Status : Completed
First Posted : December 13, 2016
Results First Posted : April 27, 2020
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
Esperion Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hypercholesterolemia
Atherosclerotic Cardiovascular Disease
Interventions Drug: bempedoic acid
Drug: placebo
Enrollment 779
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.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 257 522
Completed 250 490
Not Completed 7 32
Reason Not Completed
Death             3             8
Protocol Violation             0             3
Physician Decision             0             1
Moved out of the country             0             1
Adverse Event             2             2
Withdrawal by Subject             1             7
Could not attend study visits             0             1
Lost to Follow-up             1             9
Arm/Group Title Placebo Bempedoic Acid Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 257 522 779
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 257 participants 522 participants 779 participants
64.7  (8.73) 64.1  (8.82) 64.3  (8.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
Female
89
  34.6%
194
  37.2%
283
  36.3%
Male
168
  65.4%
328
  62.8%
496
  63.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
American Indian or Alaska Native
1
   0.4%
0
   0.0%
1
   0.1%
Asian
0
   0.0%
4
   0.8%
4
   0.5%
Black or African American
12
   4.7%
24
   4.6%
36
   4.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.2%
1
   0.1%
White
244
  94.9%
491
  94.1%
735
  94.4%
Multiple
0
   0.0%
2
   0.4%
2
   0.3%
Mean low-density lipoprotein cholesterol (LDL-C)   [1] 
Mean (Standard Deviation)
Unit of measure:  Milligrams per deciliter (mg/dL)
Number Analyzed 257 participants 522 participants 779 participants
122.4  (38.30) 119.4  (37.75) 120.43  (37.931)
[1]
Measure Description: Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1.
LDL-C category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
<130 mg/dL
173
  67.3%
365
  69.9%
538
  69.1%
≥130 and <160 mg/dL
45
  17.5%
89
  17.0%
134
  17.2%
≥160 mg/dL
39
  15.2%
68
  13.0%
107
  13.7%
Mean non-high-density lipoprotein cholesterol (non-HDL-C)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 257 participants 522 participants 779 participants
153.7  (44.36) 150.7  (42.75) 151.7  (43.28)
[1]
Measure Description: 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.
Mean total cholesterol (TC)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 257 participants 522 participants 779 participants
204.8  (46.06) 202.1  (42.71) 203.0  (43.83)
[1]
Measure Description: Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1.
Mean apolipoprotein B (apoB)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 257 participants 522 participants 779 participants
118.6  (30.53) 116.2  (29.58) 117.0  (29.90)
[1]
Measure Description: Baseline was defined as the last non-missing value on or prior to Day 1.
Median high-sensitivity C-reactive protein (hsCRP)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Milligrams per Liter
Number Analyzed 257 participants 522 participants 779 participants
1.880
(0.920 to 3.790)
1.610
(0.870 to 3.455)
1.700
(0.870 to 3.560)
[1]
Measure Description: Baseline was defined as the last non-missing value on or prior to Day 1. Dispersion data are reported as the first quartile and third quartile values.
Median triglycerides  
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 257 participants 522 participants 779 participants
143.00
(106.00 to 189.00)
139.25
(102.50 to 190.00)
140.00
(103.00 to 189.50)
Concomitant lipid-modifying therapy (LMT) medications   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
Statins
232
  90.3%
478
  91.6%
710
  91.1%
Fibrates
17
   6.6%
26
   5.0%
43
   5.5%
Nicotinic acid and derivatives
0
   0.0%
1
   0.2%
1
   0.1%
Other lipidmodifying therapies
38
  14.8%
63
  12.1%
101
  13.0%
Bile acid sequestrants
3
   1.2%
5
   1.0%
8
   1.0%
[1]
Measure Description: Concomitant medications were defined as medications that were ongoing at the time of double-blind investigational medicinal product (IMP) initiation or new medications that started after double-blind IMP initiation and within 30 days following the date of the last dose of IMP. Other LMT included ezetimibe, fish oil, omega-3 fatty acids, omega-3-acid ethyl ester, alirocumab, evolocumab, and kolestop. Data are reported for participants who took at least one concomitant LMT.
History of atherosclerotic cardiovascular disease (ASCVD)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
241
  93.8%
495
  94.8%
736
  94.5%
[1]
Measure Description: Data for participants with ASCVD only (without heterozygous familial hypercholesterolemia [HeFH]) are reported.
History of HeFH   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
16
   6.2%
27
   5.2%
43
   5.5%
[1]
Measure Description: Data for participants with HeFH (with or without ASCVD) are reported.
History of impaired fasting glucose  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
5
   1.9%
9
   1.7%
14
   1.8%
Background LMT  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
Statins with or without other LMTs
228
  88.7%
470
  90.0%
698
  89.6%
Statins without other LMTs
196
  76.3%
416
  79.7%
612
  78.6%
Statins with other LMTs
32
  12.5%
54
  10.3%
86
  11.0%
Other LMTs without statins
15
   5.8%
22
   4.2%
37
   4.7%
No LMT or statin
14
   5.4%
30
   5.7%
44
   5.6%
Disease history   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
Hypertension
224
  87.2%
438
  83.9%
662
  85.0%
Coronary heart disease
205
  79.8%
432
  82.8%
637
  81.8%
Diabetes
81
  31.5%
155
  29.7%
236
  30.3%
Impaired fasting glucose
5
   1.9%
9
   1.7%
14
   1.8%
[1]
Measure Description: The presence of these conditions was determined by participant-reported medical history.
Body mass index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per meters squared (kg/m^2)
Number Analyzed 257 participants 522 participants 779 participants
30.64  (5.048) 30.01  (5.192) 30.22  (5.150)
[1]
Measure Description: BMI was calculated as weight in kilograms divided by height in meters squared.
Estimated glomerular filtration rate (eGFR) category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
≥90 mL/min/1.73 m^2
56
  21.8%
107
  20.5%
163
  20.9%
≥60 to <90 mL/min/1.73 m^2
164
  63.8%
338
  64.8%
502
  64.4%
<60 mL/min/1.73 m^2
37
  14.4%
77
  14.8%
114
  14.6%
[1]
Measure Description: eGFR was measured in milliliters per minutes per 1.73 meters squared (mL/min/1.73 m^2).
Statin intensity   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
Low intensity or no statin
40
  15.6%
78
  14.9%
118
  15.1%
Moderate intensity
82
  31.9%
166
  31.8%
248
  31.8%
High intensity
135
  52.5%
278
  53.3%
413
  53.0%
[1]
Measure Description: Baseline statin intensity were based on stratification at randomization. Low-intensity statins: simvastatin 10 milligrams (mg); pravastatin 10-20 mg; lovastatin 20 mg; fluvastatin 20-40 mg; pitavastatin 1 mg. Moderate-intensity statins: atorvastatin 10-20 mg; rosuvastatin 5-10 mg; simvastatin 20 mg; pravastatin 40-80 mg; lovastatin 40 mg; fluvastatin XL 80 mg; fluvastatin 40 mg twice a day; pitavastatin 2-4 mg. High-intensity statins: atorvastatin 40-80 mg; rosuvastatin 20-40 mg.
Numer of participants receiving ezetimibe  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 522 participants 779 participants
24
   9.3%
39
   7.5%
63
   8.1%
1.Primary Outcome
Title Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 522
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.35  (1.446) -15.07  (1.073)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -17.42
Confidence Interval (2-Sided) 95%
-20.951 to -13.896
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.800
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline to Week 24 in LDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 522
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.66  (1.910) -12.10  (1.479)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -14.77
Confidence Interval (2-Sided) 95%
-19.504 to -10.027
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.418
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 522
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.28  (1.351) -10.75  (0.952)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -13.03
Confidence Interval (2-Sided) 95%
-16.270 to -9.794
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.652
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 522
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.26  (1.010) -9.94  (0.688)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -11.20
Confidence Interval (2-Sided) 95%
-13.599 to -8.801
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.224
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 522
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.73  (1.340) -9.29  (0.851)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -13.02
Confidence Interval (2-Sided) 95%
-16.130 to -9.907
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.587
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 240 467
Median (Inter-Quartile Range)
Unit of Measure: percent change
-9.366
(-36.320 to 35.241)
-18.699
(-46.067 to 23.864)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.039
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Location shift
Estimated Value -8.733
Confidence Interval (2-Sided) 95%
-17.238 to -0.434
Estimation Comments The location shift and asymptotic 95% confidence interval are based on Hodges-Lehman estimation.
7.Secondary Outcome
Title Change From Baseline to Week 12 in LDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 498
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.0  (30.62) -21.2  (30.82)
8.Secondary Outcome
Title Change From Baseline to Week 24 in LDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 485
Mean (Standard Deviation)
Unit of Measure: mg/dL
-1.0  (37.51) -18.7  (35.76)
9.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 499
Least Squares Mean (Standard Error)
Unit of Measure: percent change
6.12  (2.294) 11.01  (2.312)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value 4.89
Confidence Interval (2-Sided) 95%
-1.504 to 11.292
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.258
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 12 in HDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 253 499
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.25  (0.864) -6.38  (0.741)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -6.13
Confidence Interval (2-Sided) 95%
-8.369 to -3.896
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.139
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 52 in LDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 467
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.97  (1.830) -13.24  (1.412)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -12.27
Confidence Interval (2-Sided) 95%
-16.813 to -7.722
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.314
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 24 in Non-HDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 485
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.44  (1.611) -10.19  (1.200)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -12.63
Confidence Interval (2-Sided) 95%
-16.580 to -8.682
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.010
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 52 in Non-HDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 467
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.42  (1.605) -10.34  (1.150)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -9.92
Confidence Interval (2-Sided) 95%
-13.803 to -6.037
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.976
Estimation Comments [Not Specified]
14.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 24 in TC
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 486
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.52  (1.216) -9.25  (0.857)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -10.77
Confidence Interval (2-Sided) 95%
-13.698 to -7.848
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.489
Estimation Comments [Not Specified]
15.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 52 in TC
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 467
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.89  (1.199) -10.25  (0.828)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -8.36
Confidence Interval (2-Sided) 95%
-11.223 to -5.493
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.458
Estimation Comments [Not Specified]
16.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 24 in Apo B
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 144 294
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.39  (2.090) -8.61  (1.267)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -13.00
Confidence Interval (2-Sided) 95%
-17.829 to -8.175
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.451
Estimation Comments [Not Specified]
17.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 52 in Apo B
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 464
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.01  (1.502) -6.56  (0.983)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -9.58
Confidence Interval (2-Sided) 95%
-13.107 to -6.047
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.796
Estimation Comments [Not Specified]
18.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 24 in hsCRP
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 127 271
Median (Inter-Quartile Range)
Unit of Measure: percent change
1.563
(-32.174 to 47.500)
-24.107
(-51.502 to 14.035)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Location shift
Estimated Value -21.278
Confidence Interval (2-Sided) 95%
-32.250 to -10.034
Estimation Comments The location shift and asymptotic 95% confidence interval are based on Hodges-Lehman estimation.
19.Other Pre-specified Outcome
Title Percent Change From Baseline to Week 52 in hsCRP
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 465
Median (Inter-Quartile Range)
Unit of Measure: percent change
-6.250
(-39.286 to 41.810)
-16.727
(-50.877 to 31.429)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Location shift
Estimated Value -7.587
Confidence Interval (2-Sided) 95%
-16.978 to 1.653
Estimation Comments The location shift and asymptotic 95% confidence interval are based on Hodges-Lehman estimation.
20.Other Pre-specified Outcome
Title Change From Baseline to Week 52 in LDL-C
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only participants with available data were analyzed.
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 237 467
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-4.71  (2.216) -19.78  (1.433)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Bempedoic Acid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS mean
Estimated Value -15.07
Confidence Interval (2-Sided) 95%
-20.260 to -9.878
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.641
Estimation Comments [Not Specified]
Time Frame up to Week 52
Adverse Event Reporting Description Treatment-emergent events, defined as those adverse events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after the last dose of IMP, were collected and reported. The analysis was performed using the Safety Analysis Set, comprised of all randomized participants who received >=1 dose of IMP.
 
Arm/Group Title Placebo Bempedoic Acid
Hide Arm/Group Description Participants received 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. 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.
All-Cause Mortality
Placebo Bempedoic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   2/257 (0.78%)   6/522 (1.15%) 
Hide Serious Adverse Events
Placebo Bempedoic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   48/257 (18.68%)   106/522 (20.31%) 
Blood and lymphatic system disorders     
Microcytic anaemia  1  1/257 (0.39%)  0/522 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  1/257 (0.39%)  0/522 (0.00%) 
Acute left ventricular failure  1  1/257 (0.39%)  0/522 (0.00%) 
Acute myocardial infarction  1  3/257 (1.17%)  2/522 (0.38%) 
Angina pectoris  1  1/257 (0.39%)  12/522 (2.30%) 
Angina unstable  1  6/257 (2.33%)  9/522 (1.72%) 
Arteriosclerosis coronary artery  1  0/257 (0.00%)  2/522 (0.38%) 
Atrial fibrillation  1  1/257 (0.39%)  4/522 (0.77%) 
Atrioventricular block second degree  1  1/257 (0.39%)  1/522 (0.19%) 
Cardiac arrest  1  2/257 (0.78%)  2/522 (0.38%) 
Cardiac failure  1  2/257 (0.78%)  0/522 (0.00%) 
Cardiac failure chronic  1  1/257 (0.39%)  4/522 (0.77%) 
Cardiac failure congestive  1  0/257 (0.00%)  2/522 (0.38%) 
Cardiovascular disorder  1  0/257 (0.00%)  1/522 (0.19%) 
Coronary artery disease  1  6/257 (2.33%)  7/522 (1.34%) 
Coronary artery occlusion  1  0/257 (0.00%)  1/522 (0.19%) 
Coronary artery stenosis  1  0/257 (0.00%)  1/522 (0.19%) 
Myocardial infarction  1  2/257 (0.78%)  2/522 (0.38%) 
Myocardial ischaemia  1  4/257 (1.56%)  2/522 (0.38%) 
Ventricular arrhythmia  1  1/257 (0.39%)  0/522 (0.00%) 
Ventricular fibrillation  1  0/257 (0.00%)  1/522 (0.19%) 
Ear and labyrinth disorders     
Vertigo  1  0/257 (0.00%)  1/522 (0.19%) 
Vertigo positional  1  0/257 (0.00%)  1/522 (0.19%) 
Gastrointestinal disorders     
Abdominal pain upper  1  1/257 (0.39%)  0/522 (0.00%) 
Colitis ulcerative  1  0/257 (0.00%)  1/522 (0.19%) 
Dyspepsia  1  0/257 (0.00%)  1/522 (0.19%) 
Gastric antral vascular ectasia  1  0/257 (0.00%)  1/522 (0.19%) 
Gastritis  1  0/257 (0.00%)  1/522 (0.19%) 
Hiatus hernia  1  1/257 (0.39%)  0/522 (0.00%) 
Ileus  1  0/257 (0.00%)  1/522 (0.19%) 
Ileus paralytic  1  0/257 (0.00%)  1/522 (0.19%) 
Inguinal hernia  1  0/257 (0.00%)  1/522 (0.19%) 
Intestinal perforation  1  0/257 (0.00%)  1/522 (0.19%) 
Large intestine perforation  1  0/257 (0.00%)  1/522 (0.19%) 
Oesophageal obstruction  1  0/257 (0.00%)  1/522 (0.19%) 
Oesophagitis  1  1/257 (0.39%)  0/522 (0.00%) 
Peritoneal adhesions  1  1/257 (0.39%)  0/522 (0.00%) 
General disorders     
Asthenia  1  1/257 (0.39%)  0/522 (0.00%) 
Chest pain  1  0/257 (0.00%)  2/522 (0.38%) 
Death  1  0/257 (0.00%)  1/522 (0.19%) 
Exercise tolerance decreased  1  1/257 (0.39%)  0/522 (0.00%) 
Non-cardiac chest pain  1  2/257 (0.78%)  1/522 (0.19%) 
Pain  1  0/257 (0.00%)  1/522 (0.19%) 
Vascular stent occlusion  1  1/257 (0.39%)  1/522 (0.19%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/257 (0.00%)  1/522 (0.19%) 
Cholelithiasis  1  1/257 (0.39%)  2/522 (0.38%) 
Hepatic cirrhosis  1  1/257 (0.39%)  0/522 (0.00%) 
Infections and infestations     
Cellulitis  1  1/257 (0.39%)  0/522 (0.00%) 
Clostridium difficile infection  1  0/257 (0.00%)  1/522 (0.19%) 
Cystitis  1  0/257 (0.00%)  1/522 (0.19%) 
Diverticulitis  1  1/257 (0.39%)  1/522 (0.19%) 
Fungal infection  1  1/257 (0.39%)  0/522 (0.00%) 
Gastroenteritis  1  0/257 (0.00%)  1/522 (0.19%) 
Lower respiratory tract infection  1  1/257 (0.39%)  1/522 (0.19%) 
Pneumonia  1  1/257 (0.39%)  2/522 (0.38%) 
Pneumonia bacterial  1  0/257 (0.00%)  1/522 (0.19%) 
Septic shock  1  0/257 (0.00%)  1/522 (0.19%) 
Urethral stricture post infection  1  0/257 (0.00%)  1/522 (0.19%) 
Urinary tract infection  1  0/257 (0.00%)  3/522 (0.57%) 
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  0/257 (0.00%)  1/522 (0.19%) 
Brain contusion  1  0/257 (0.00%)  1/522 (0.19%) 
Contusion  1  1/257 (0.39%)  0/522 (0.00%) 
Coronary artery restenosis  1  0/257 (0.00%)  1/522 (0.19%) 
Femoral neck fracture  1  1/257 (0.39%)  0/522 (0.00%) 
Gas poisoning  1  0/257 (0.00%)  1/522 (0.19%) 
Kidney rupture  1  0/257 (0.00%)  1/522 (0.19%) 
Limb injury  1  0/257 (0.00%)  1/522 (0.19%) 
Meniscus injury  1  0/257 (0.00%)  1/522 (0.19%) 
Postoperative thoracic procedure complication  1  0/257 (0.00%)  1/522 (0.19%) 
Procedural pain  1  0/257 (0.00%)  1/522 (0.19%) 
Tendon rupture  1  0/257 (0.00%)  3/522 (0.57%) 
Vascular pseudoaneurysm  1  0/257 (0.00%)  1/522 (0.19%) 
Investigations     
Ejection fraction decreased  1  1/257 (0.39%)  0/522 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/257 (0.00%)  1/522 (0.19%) 
Hyperkalaemia  1  0/257 (0.00%)  1/522 (0.19%) 
Hypokalaemia  1  1/257 (0.39%)  0/522 (0.00%) 
Lactic acidosis  1  0/257 (0.00%)  1/522 (0.19%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/257 (0.00%)  2/522 (0.38%) 
Intervertebral disc disorder  1  0/257 (0.00%)  1/522 (0.19%) 
Musculoskeletal chest pain  1  0/257 (0.00%)  1/522 (0.19%) 
Osteoarthritis  1  2/257 (0.78%)  5/522 (0.96%) 
Periostitis  1  0/257 (0.00%)  1/522 (0.19%) 
Spinal column stenosis  1  0/257 (0.00%)  1/522 (0.19%) 
Spondylitis  1  0/257 (0.00%)  1/522 (0.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  1/257 (0.39%)  1/522 (0.19%) 
Colon adenoma  1  0/257 (0.00%)  1/522 (0.19%) 
Lymphoma  1  0/257 (0.00%)  1/522 (0.19%) 
Malignant melanoma  1  1/257 (0.39%)  0/522 (0.00%) 
Neuroendocrine tumour of the lung  1  0/257 (0.00%)  1/522 (0.19%) 
Non-small cell lung cancer  1  1/257 (0.39%)  0/522 (0.00%) 
Renal cancer  1  0/257 (0.00%)  1/522 (0.19%) 
Squamous cell carcinoma of skin  1  0/257 (0.00%)  1/522 (0.19%) 
Nervous system disorders     
Carotid artery stenosis  1  0/257 (0.00%)  1/522 (0.19%) 
Carpal tunnel syndrome  1  1/257 (0.39%)  0/522 (0.00%) 
Cervical radiculopathy  1  0/257 (0.00%)  1/522 (0.19%) 
Encephalopathy  1  0/257 (0.00%)  1/522 (0.19%) 
Hyporeflexia  1  0/257 (0.00%)  1/522 (0.19%) 
Ischaemic stroke  1  2/257 (0.78%)  4/522 (0.77%) 
Post stroke epilepsy  1  0/257 (0.00%)  1/522 (0.19%) 
Syncope  1  0/257 (0.00%)  4/522 (0.77%) 
Psychiatric disorders     
Alcohol withdrawal syndrome  1  0/257 (0.00%)  1/522 (0.19%) 
Depression  1  1/257 (0.39%)  0/522 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  0/257 (0.00%)  1/522 (0.19%) 
Perinephritis  1  0/257 (0.00%)  1/522 (0.19%) 
Urinary incontinence  1  0/257 (0.00%)  1/522 (0.19%) 
Urinary retention  1  0/257 (0.00%)  1/522 (0.19%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/257 (0.00%)  1/522 (0.19%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/257 (0.00%)  1/522 (0.19%) 
Chronic obstructive pulmonary disease  1  1/257 (0.39%)  1/522 (0.19%) 
Dyspnoea  1  4/257 (1.56%)  0/522 (0.00%) 
Dyspnoea exertional  1  1/257 (0.39%)  1/522 (0.19%) 
Pulmonary embolism  1  0/257 (0.00%)  1/522 (0.19%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  1/257 (0.39%)  0/522 (0.00%) 
Skin necrosis  1  0/257 (0.00%)  1/522 (0.19%) 
Surgical and medical procedures     
Supportive care  1  0/257 (0.00%)  1/522 (0.19%) 
Vascular disorders     
Aortic aneurysm  1  0/257 (0.00%)  1/522 (0.19%) 
Deep vein thrombosis  1  1/257 (0.39%)  0/522 (0.00%) 
Iliac artery occlusion  1  1/257 (0.39%)  0/522 (0.00%) 
Peripheral arterial occlusive disease  1  1/257 (0.39%)  2/522 (0.38%) 
Peripheral artery stenosis  1  0/257 (0.00%)  1/522 (0.19%) 
Peripheral ischaemia  1  0/257 (0.00%)  1/522 (0.19%) 
Subclavian artery thrombosis  1  1/257 (0.39%)  0/522 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Bempedoic Acid
Affected / at Risk (%) Affected / at Risk (%)
Total   88/257 (34.24%)   211/522 (40.42%) 
Blood and lymphatic system disorders     
Anaemia  1  3/257 (1.17%)  14/522 (2.68%) 
Gastrointestinal disorders     
Diarrhoea  1  7/257 (2.72%)  16/522 (3.07%) 
General disorders     
Fatigue  1  9/257 (3.50%)  6/522 (1.15%) 
Infections and infestations     
Bronchitis  1  6/257 (2.33%)  7/522 (1.34%) 
Lower respiratory tract infection  1  7/257 (2.72%)  7/522 (1.34%) 
Nasopharyngitis  1  13/257 (5.06%)  27/522 (5.17%) 
Upper respiratory tract infection  1  9/257 (3.50%)  19/522 (3.64%) 
Urinary tract infection  1  5/257 (1.95%)  24/522 (4.60%) 
Investigations     
Blood uric acid increased  1  1/257 (0.39%)  14/522 (2.68%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  6/257 (2.33%)  10/522 (1.92%) 
Gout  1  2/257 (0.78%)  11/522 (2.11%) 
Hyperuricaemia  1  5/257 (1.95%)  22/522 (4.21%) 
Type 2 diabetes mellitus  1  7/257 (2.72%)  10/522 (1.92%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  8/257 (3.11%)  18/522 (3.45%) 
Muscle spasms  1  3/257 (1.17%)  11/522 (2.11%) 
Myalgia  1  8/257 (3.11%)  15/522 (2.87%) 
Osteoarthritis  1  3/257 (1.17%)  11/522 (2.11%) 
Pain in extremity  1  1/257 (0.39%)  11/522 (2.11%) 
Nervous system disorders     
Dizziness  1  9/257 (3.50%)  8/522 (1.53%) 
Headache  1  7/257 (2.72%)  10/522 (1.92%) 
Vascular disorders     
Hypertension  1  6/257 (2.33%)  7/522 (1.34%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If the Principal Investigator plans to publish information from the study, a copy of the manuscript should be provided to the Sponsor for review before submission for publication or presentation. The Sponsor may request that that publication be withheld.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Esperion Therapeutics, Inc.
Phone: 1-833-377-7633
EMail: medinfo@esperion.com
Publications:
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396.
Layout table for additonal information
Responsible Party: Esperion Therapeutics
ClinicalTrials.gov Identifier: NCT02991118    
Other Study ID Numbers: 1002-047
2016-003486-26 ( EudraCT Number )
First Submitted: December 9, 2016
First Posted: December 13, 2016
Results First Submitted: March 20, 2020
Results First Posted: April 27, 2020
Last Update Posted: April 27, 2020