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Trial record 1 of 1 for:    1002FDC-053
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A Study Evaluating the Safety and Efficacy of Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo in Patients Treated With Maximally Tolerated Statin Therapy

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: NCT03337308
Recruitment Status : Completed
First Posted : November 8, 2017
Results First Posted : April 8, 2020
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Esperion Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hyperlipidemias
Interventions Combination Product: Bempedoic Acid + Ezetimibe Fixed-Dose Combination
Drug: Bempedoic Acid
Drug: Ezetimibe
Drug: Placebos
Enrollment 382
Recruitment Details  
Pre-assignment Details Data are presented for the Full Analysis Set, comprised of all randomized participants. One participant was randomized but was not treated.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks. Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks. Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks. Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Period Title: Overall Study
Started 108 110 109 55
Completed 103 103 104 53
Not Completed 5 7 5 2
Reason Not Completed
Adverse Event             2             3             3             1
Lost to Follow-up             1             2             0             0
Withdrawal by Subject             2             1             2             1
Protocol Violation             0             1             0             0
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo Total
Hide Arm/Group Description Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks. Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks. Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks. Participants received placebo to match the bempedoic acid + ezetimibe FDC 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 108 110 109 55 382
Hide Baseline Analysis Population Description
Data are presented for the Full Analysis Set, comprised of all randomized participants. One participant was randomized but was not treated.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 108 participants 110 participants 109 participants 55 participants 382 participants
63.0  (9.97) 65.2  (9.54) 64.4  (8.91) 65.6  (10.74) 64.4  (9.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 110 participants 109 participants 55 participants 382 participants
Female
58
  53.7%
65
  59.1%
57
  52.3%
22
  40.0%
202
  52.9%
Male
50
  46.3%
45
  40.9%
52
  47.7%
33
  60.0%
180
  47.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 110 participants 109 participants 55 participants 382 participants
Hispanic or Latino
32
  29.6%
33
  30.0%
32
  29.4%
20
  36.4%
117
  30.6%
Not Hispanic or Latino
76
  70.4%
77
  70.0%
77
  70.6%
35
  63.6%
265
  69.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 110 participants 109 participants 55 participants 382 participants
American Indian or Alaska Native
1
   0.9%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
Asian
2
   1.9%
1
   0.9%
1
   0.9%
0
   0.0%
4
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.9%
0
   0.0%
1
   0.3%
Black or African American
20
  18.5%
19
  17.3%
16
  14.7%
7
  12.7%
62
  16.2%
White
85
  78.7%
90
  81.8%
91
  83.5%
48
  87.3%
314
  82.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Low-density lipoprotein cholesterol (LDL-C)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Milligrams per deciliter (mg/dL)
Number Analyzed 86 participants 88 participants 86 participants 41 participants 301 participants
153.80  (40.526) 145.13  (38.456) 148.80  (41.839) 152.80  (46.773) 149.70  (41.162)
[1]
Measure Description: Baseline was defined as the mean of the last 2 non-missing values from Week -2 (Screening Visit [Visit S1]) and predose Day 1/Week 0 (Treatment Visit 1 [Visit T1]).
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
Non-high-density lipoprotein cholesterol (non-HDL-C)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 86 participants 88 participants 86 participants 41 participants 301 participants
188.22  (46.657) 175.67  (40.474) 180.18  (47.308) 180.91  (49.720) 181.26  (45.595)
[1]
Measure Description: Baseline was defined as the mean of the last 2 non-missing values from Week -2 (Screening Visit [Visit S1]) and predose Day 1/Week 0 (Treatment Visit 1 [Visit T1]).
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
Total cholesterol (TC)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 86 participants 88 participants 86 participants 41 participants 301 participants
237.32  (48.694) 225.55  (43.165) 231.41  (50.478) 231.27  (50.210) 231.36  (47.857)
[1]
Measure Description: Baseline was defined as the mean of the last 2 non-missing values from Week -2 (Screening Visit [Visit S1]) and predose Day 1/Week 0 (Treatment Visit 1 [Visit T1]).
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
Apolipoprotein B (apo B)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 82 participants 85 participants 84 participants 38 participants 289 participants
121.1  (30.85) 113.4  (26.43) 115.5  (31.30) 115.1  (32.52) 116.4  (29.98)
[1]
Measure Description: Baseline was defined as the predose Day 1/Week 0 (Visit T1) value.
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed. Only participants with available data were analyzed.
High-sensitivity C-reactive protein (hsCRP)   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Milligrams per liter (mg/L)
Number Analyzed 84 participants 87 participants 85 participants 40 participants 296 participants
3.08
(1.68 to 6.20)
2.91
(1.40 to 5.04)
2.78
(1.30 to 5.89)
3.01
(1.26 to 5.51)
2.96
(1.40 to 5.78)
[1]
Measure Description: Baseline was defined as the predose Day 1/Week 0 (Visit T1) value.
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed. Only participants with available data were analyzed.
Triglycerides (TGs)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 86 participants 88 participants 86 participants 41 participants 301 participants
177.19  (94.904) 156.65  (71.985) 161.73  (79.924) 144.59  (55.814) 162.33  (79.973)
[1]
Measure Description: Baseline was defined as the mean of the last 2 non-missing values from Week -2 (Screening Visit [Visit S1]) and predose Day 1/Week 0 (Treatment Visit 1 [Visit T1]).
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
High-density lipoprotein cholesterol (HDL-C)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 86 participants 88 participants 86 participants 41 participants 301 participants
49.19  (14.566) 49.89  (12.383) 51.23  (15.902) 50.40  (14.067) 50.14  (14.256)
[1]
Measure Description: Baseline was defined as the mean of the last 2 non-missing values from Week -2 (Screening Visit [Visit S1]) and predose Day 1/Week 0 (Treatment Visit 1 [Visit T1]).
[2]
Measure Analysis Population Description: After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
1.Primary Outcome
Title Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Hide Description 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 Week -2 and predose Day 1/Week 0. Percent change from baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group and randomization stratification as a factors and baseline LDL-C as a covariate. Percent change from baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. For LDL-C, if measured LDL-C value was available, measured LDL-C was used.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), also known as the intention-to-treat set, was defined as all randomized participants. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 86 88 86 41
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
-36.2  (2.56) -17.2  (2.52) -23.2  (2.18) 1.8  (3.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Placebo
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 of Least Squares (LS) means
Estimated Value -38.0
Confidence Interval (2-Sided) 95%
-46.5 to -29.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.32
Estimation Comments Standard Error of the Difference of Least Squares (LS) Means
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Bempedoic Acid 180 mg
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 of LS means
Estimated Value -19.0
Confidence Interval (2-Sided) 95%
-26.1 to -11.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.60
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Ezetimibe 10 mg
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 of LS means
Estimated Value -13.1
Confidence Interval (2-Sided) 95%
-19.7 to -6.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.37
Estimation Comments Standard Error of the Difference of LS Means
2.Secondary Outcome
Title Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Hide Description Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in hsCRP was analyzed using a non-parametric analysis. Percent change from baseline was calculated as: ([hsCRP value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with available data were analyzed. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice;therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 80 81 79 39
Median (Inter-Quartile Range)
Unit of Measure: Percent Change
-35.1
(-56.5 to -2.3)
-31.9
(-62.6 to 7.7)
-8.2
(-34.4 to 32.0)
21.6
(-18.5 to 68.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.01
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Location shift
Estimated Value -46.1
Confidence Interval (2-Sided) 99%
-78.75 to -15.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 12.22
Estimation Comments Standard Error of the Hodges-Lehmann Median Difference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Ezetimibe 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments using alpha = 0.02
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -25.6
Confidence Interval (2-Sided) 98%
-45.00 to -7.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.14
Estimation Comments Standard Error of the Hodges-Lehmann Median Difference
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Bempedoic Acid 180 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments using alpha = 0.02
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -2.6
Confidence Interval (2-Sided) 98%
-21.35 to 16.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.08
Estimation Comments Standard Error of the Hodges-Lehmann Median Difference
3.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Hide Description 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 Week -2 and predose Day 1/Week 0. Percent change from baseline in non-HDL-C was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline non-HDL-C as a covariate. Percent change from baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 86 88 86 41
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-31.9  (2.23) -14.1  (2.17) -19.9  (2.05) 1.8  (3.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments using alpha = 0.01
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 -33.7
Confidence Interval (2-Sided) 99%
-43.9 to -23.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.97
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Bempedoic Acid 180 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -17.8
Confidence Interval (2-Sided) 98%
-25.1 to -10.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.12
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Ezetimibe 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -12.1
Confidence Interval (2-Sided) 98%
-19.1 to -5.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.03
Estimation Comments Standard Error of the Difference of LS Means
4.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Hide Description 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 Week -2 and predose Day 1/Week 0. Percent change from baseline in TC was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline TC as a covariate. Percent change from baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with available data were analyzed. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 86 88 86 41
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-26.4  (1.90) -12.1  (1.83) -16.0  (1.59) 0.7  (2.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.01
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -27.1
Confidence Interval (2-Sided) 99%
-35.1 to -19.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.11
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Bempedoic Acid 180 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -14.2
Confidence Interval (2-Sided) 98%
-20.4 to -8.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.64
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Ezetimibe 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -10.4
Confidence Interval (2-Sided) 98%
-16.1 to -4.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.48
Estimation Comments Standard Error of the Difference of LS Means
5.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)
Hide Description Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apo B. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in apo B was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline apo B as a covariate. Percent change from baseline was calculated as: ([apo B value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed. Only participants with available data were analyzed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 82 85 84 38
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-24.6  (2.38) -11.8  (2.18) -15.3  (1.97) 5.5  (2.97)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.01
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -30.1
Confidence Interval (2-Sided) 99%
-39.9 to -20.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.81
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Bempedoic Acid 180 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -12.8
Confidence Interval (2-Sided) 98%
-20.3 to -5.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.23
Estimation Comments Standard Error of the Difference of LS Means
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC, Ezetimibe 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments using alpha = 0.02
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of LS means
Estimated Value -9.3
Confidence Interval (2-Sided) 98%
-16.5 to -2.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.09
Estimation Comments Standard Error of the Difference of LS Means
6.Secondary Outcome
Title Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
Hide Description 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 Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with available data were analyzed. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 83 82 80 40
Mean (Standard Deviation)
Unit of Measure: Percent change
-5.59  (12.269) -5.40  (14.688) -2.11  (11.590) -0.54  (12.799)
7.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Hide Description 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 Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([TGs value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with available data were analyzed. After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all efficacy data from these sites removed.
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description:
Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.
Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.
Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.
Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
Overall Number of Participants Analyzed 83 82 80 40
Mean (Standard Deviation)
Unit of Measure: Percent change
-7.90  (25.633) 7.94  (42.312) -2.46  (33.402) 5.47  (31.992)
Time Frame Up to approximately 14 weeks
Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) that began or worsened after the first dose of investigational medicinal product (IMP). The analysis was performed using the Safety Analysis Set which consists of all randomized participants who received at least 1 dose of blinded IMP.
 
Arm/Group Title Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Hide Arm/Group Description Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks. Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks. Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks. Participants received placebo to match the bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, the bempedoic acid 180 mg tablet, or the ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks.
All-Cause Mortality
Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/107 (0.00%)   0/110 (0.00%)   0/109 (0.00%)   0/55 (0.00%) 
Hide Serious Adverse Events
Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/107 (7.48%)   7/110 (6.36%)   10/109 (9.17%)   1/55 (1.82%) 
Cardiac disorders         
Acute myocardial infarction † 1  1/107 (0.93%)  2/110 (1.82%)  3/109 (2.75%)  0/55 (0.00%) 
Angina pectoris † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Atrial fibrillation † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Cardiac failure congestive † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Coronary artery disease † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  1/55 (1.82%) 
Myocardial infarction † 1  0/107 (0.00%)  1/110 (0.91%)  0/109 (0.00%)  1/55 (1.82%) 
Myocardial ischaemia † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Supraventricular tachycardia † 1  0/107 (0.00%)  1/110 (0.91%)  0/109 (0.00%)  0/55 (0.00%) 
General disorders         
Non-cardiac chest pain † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Infections and infestations         
Diverticulitis † 1  0/107 (0.00%)  1/110 (0.91%)  0/109 (0.00%)  0/55 (0.00%) 
Pneumonia † 1  0/107 (0.00%)  1/110 (0.91%)  1/109 (0.92%)  0/55 (0.00%) 
Rhinovirus infection † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Injury, poisoning and procedural complications         
Coronary vascular graft stenosis † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Limb injury † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Ovarian cancer † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Nervous system disorders         
Hemiparesis † 1  1/107 (0.93%)  0/110 (0.00%)  0/109 (0.00%)  0/55 (0.00%) 
Psychiatric disorders         
Confusional state † 1  0/107 (0.00%)  1/110 (0.91%)  0/109 (0.00%)  0/55 (0.00%) 
Renal and urinary disorders         
Renal artery occlusion † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease † 1  0/107 (0.00%)  1/110 (0.91%)  0/109 (0.00%)  0/55 (0.00%) 
Respiratory failure † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Chronic respiratory failure † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (0.00%) 
Vascular disorders         
Deep vein thrombosis † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  0/55 (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 3%
Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Bempedoic Acid 180 mg Ezetimibe 10 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/107 (24.30%)   27/110 (24.55%)   26/109 (23.85%)   12/55 (21.82%) 
Blood and lymphatic system disorders         
Anaemia † 1  1/107 (0.93%)  2/110 (1.82%)  1/109 (0.92%)  2/55 (3.64%) 
Gastrointestinal disorders         
Constipation † 1  4/107 (3.74%)  0/110 (0.00%)  2/109 (1.83%)  0/55 (0.00%) 
Infections and infestations         
Nasopharyngitis † 1  4/107 (3.74%)  6/110 (5.45%)  4/109 (3.67%)  1/55 (1.82%) 
Urinary tract infection † 1  8/107 (7.48%)  3/110 (2.73%)  3/109 (2.75%)  2/55 (3.64%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  1/107 (0.93%)  4/110 (3.64%)  4/109 (3.67%)  2/55 (3.64%) 
Back pain † 1  3/107 (2.80%)  3/110 (2.73%)  4/109 (3.67%)  2/55 (3.64%) 
Muscle spasms † 1  2/107 (1.87%)  1/110 (0.91%)  4/109 (3.67%)  0/55 (0.00%) 
Myalgia † 1  2/107 (1.87%)  5/110 (4.55%)  2/109 (1.83%)  1/55 (1.82%) 
Nervous system disorders         
Headache † 1  2/107 (1.87%)  4/110 (3.64%)  2/109 (1.83%)  1/55 (1.82%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  0/107 (0.00%)  0/110 (0.00%)  1/109 (0.92%)  2/55 (3.64%) 
Vascular disorders         
Hypertension † 1  3/107 (2.80%)  5/110 (4.55%)  2/109 (1.83%)  0/55 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.
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.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Esperion Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03337308    
Other Study ID Numbers: 1002FDC-053
First Submitted: November 6, 2017
First Posted: November 8, 2017
Results First Submitted: March 25, 2020
Results First Posted: April 8, 2020
Last Update Posted: April 8, 2020