Trial Outcomes & Findings for 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 (NCT NCT03337308)

Last Updated: 2020-04-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

382 participants

Primary outcome timeframe

Baseline; Week 12

Results posted on

2020-04-08

Participant Flow

Data are presented for the Full Analysis Set, comprised of all randomized participants. One participant was randomized but was not treated.

Participant milestones

Participant milestones
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo 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 Study STARTED	108	110	109	55
Overall Study COMPLETED	103	103	104	53
Overall Study NOT COMPLETED	5	7	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo 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 Study Adverse Event	2	3	3	1
Overall Study Lost to Follow-up	1	2	0	0
Overall Study Withdrawal by Subject	2	1	2	1
Overall Study Protocol Violation	0	1	0	0

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=108 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=110 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=109 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=55 Participants 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 n=382 Participants Total of all reporting groups
Age, Continuous	63.0 Years STANDARD_DEVIATION 9.97 • n=108 Participants	65.2 Years STANDARD_DEVIATION 9.54 • n=110 Participants	64.4 Years STANDARD_DEVIATION 8.91 • n=109 Participants	65.6 Years STANDARD_DEVIATION 10.74 • n=55 Participants	64.4 Years STANDARD_DEVIATION 9.68 • n=382 Participants
Sex: Female, Male Female	58 Participants n=108 Participants	65 Participants n=110 Participants	57 Participants n=109 Participants	22 Participants n=55 Participants	202 Participants n=382 Participants
Sex: Female, Male Male	50 Participants n=108 Participants	45 Participants n=110 Participants	52 Participants n=109 Participants	33 Participants n=55 Participants	180 Participants n=382 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=108 Participants	33 Participants n=110 Participants	32 Participants n=109 Participants	20 Participants n=55 Participants	117 Participants n=382 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	76 Participants n=108 Participants	77 Participants n=110 Participants	77 Participants n=109 Participants	35 Participants n=55 Participants	265 Participants n=382 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=108 Participants	0 Participants n=110 Participants	0 Participants n=109 Participants	0 Participants n=55 Participants	0 Participants n=382 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=108 Participants	0 Participants n=110 Participants	0 Participants n=109 Participants	0 Participants n=55 Participants	1 Participants n=382 Participants
Race (NIH/OMB) Asian	2 Participants n=108 Participants	1 Participants n=110 Participants	1 Participants n=109 Participants	0 Participants n=55 Participants	4 Participants n=382 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=108 Participants	0 Participants n=110 Participants	1 Participants n=109 Participants	0 Participants n=55 Participants	1 Participants n=382 Participants
Race (NIH/OMB) Black or African American	20 Participants n=108 Participants	19 Participants n=110 Participants	16 Participants n=109 Participants	7 Participants n=55 Participants	62 Participants n=382 Participants
Race (NIH/OMB) White	85 Participants n=108 Participants	90 Participants n=110 Participants	91 Participants n=109 Participants	48 Participants n=55 Participants	314 Participants n=382 Participants
Race (NIH/OMB) More than one race	0 Participants n=108 Participants	0 Participants n=110 Participants	0 Participants n=109 Participants	0 Participants n=55 Participants	0 Participants n=382 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=108 Participants	0 Participants n=110 Participants	0 Participants n=109 Participants	0 Participants n=55 Participants	0 Participants n=382 Participants
Low-density lipoprotein cholesterol (LDL-C)	153.80 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 40.526 • n=86 Participants • 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.	145.13 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 38.456 • n=88 Participants • 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.	148.80 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 41.839 • n=86 Participants • 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.	152.80 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 46.773 • n=41 Participants • 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.	149.70 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 41.162 • n=301 Participants • 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)	188.22 mg/dL STANDARD_DEVIATION 46.657 • n=86 Participants • 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.	175.67 mg/dL STANDARD_DEVIATION 40.474 • n=88 Participants • 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.	180.18 mg/dL STANDARD_DEVIATION 47.308 • n=86 Participants • 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.	180.91 mg/dL STANDARD_DEVIATION 49.720 • n=41 Participants • 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.	181.26 mg/dL STANDARD_DEVIATION 45.595 • n=301 Participants • 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)	237.32 mg/dL STANDARD_DEVIATION 48.694 • n=86 Participants • 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.	225.55 mg/dL STANDARD_DEVIATION 43.165 • n=88 Participants • 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.	231.41 mg/dL STANDARD_DEVIATION 50.478 • n=86 Participants • 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.	231.27 mg/dL STANDARD_DEVIATION 50.210 • n=41 Participants • 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.	231.36 mg/dL STANDARD_DEVIATION 47.857 • n=301 Participants • 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)	121.1 mg/dL STANDARD_DEVIATION 30.85 • n=82 Participants • 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.	113.4 mg/dL STANDARD_DEVIATION 26.43 • n=85 Participants • 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.	115.5 mg/dL STANDARD_DEVIATION 31.30 • n=84 Participants • 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.	115.1 mg/dL STANDARD_DEVIATION 32.52 • n=38 Participants • 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.	116.4 mg/dL STANDARD_DEVIATION 29.98 • n=289 Participants • 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)	3.08 milligrams per liter (mg/L) n=84 Participants • 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.	2.91 milligrams per liter (mg/L) n=87 Participants • 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.	2.78 milligrams per liter (mg/L) n=85 Participants • 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.	3.01 milligrams per liter (mg/L) n=40 Participants • 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.	2.96 milligrams per liter (mg/L) n=296 Participants • 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)	177.19 mg/dL STANDARD_DEVIATION 94.904 • n=86 Participants • 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.	156.65 mg/dL STANDARD_DEVIATION 71.985 • n=88 Participants • 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.	161.73 mg/dL STANDARD_DEVIATION 79.924 • n=86 Participants • 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.	144.59 mg/dL STANDARD_DEVIATION 55.814 • n=41 Participants • 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.	162.33 mg/dL STANDARD_DEVIATION 79.973 • n=301 Participants • 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)	49.19 mg/dL STANDARD_DEVIATION 14.566 • n=86 Participants • 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.	49.89 mg/dL STANDARD_DEVIATION 12.383 • n=88 Participants • 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.	51.23 mg/dL STANDARD_DEVIATION 15.902 • n=86 Participants • 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.	50.40 mg/dL STANDARD_DEVIATION 14.067 • n=41 Participants • 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.	50.14 mg/dL STANDARD_DEVIATION 14.256 • n=301 Participants • 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.

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=86 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=88 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=86 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=41 Participants 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.
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)	-36.2 Percent Change Standard Error 2.56	-17.2 Percent Change Standard Error 2.52	-23.2 Percent Change Standard Error 2.18	1.8 Percent Change Standard Error 3.49

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=80 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=81 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=79 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=39 Participants 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.
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)	-35.1 Percent Change Interval -56.5 to -2.3	-31.9 Percent Change Interval -62.6 to 7.7	-8.2 Percent Change Interval -34.4 to 32.0	21.6 Percent Change Interval -18.5 to 68.5

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=86 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=88 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=86 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=41 Participants 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.
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	-31.9 Percent change Standard Error 2.23	-14.1 Percent change Standard Error 2.17	-19.9 Percent change Standard Error 2.05	1.8 Percent change Standard Error 3.28

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=86 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=88 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=86 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=41 Participants 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.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	-26.4 Percent change Standard Error 1.90	-12.1 Percent change Standard Error 1.83	-16.0 Percent change Standard Error 1.59	0.7 Percent change Standard Error 2.46

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=82 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=85 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=84 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=38 Participants 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.
Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)	-24.6 Percent change Standard Error 2.38	-11.8 Percent change Standard Error 2.18	-15.3 Percent change Standard Error 1.97	5.5 Percent change Standard Error 2.97

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=83 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=82 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=80 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=40 Participants 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.
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)	-5.59 Percent change Standard Deviation 12.269	-5.40 Percent change Standard Deviation 14.688	-2.11 Percent change Standard Deviation 11.590	-0.54 Percent change Standard Deviation 12.799

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=83 Participants Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=82 Participants Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=80 Participants Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=40 Participants 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.
Percent Change From Baseline to Week 12 in Triglycerides (TGs)	-7.90 Percent change Standard Deviation 25.633	7.94 Percent change Standard Deviation 42.312	-2.46 Percent change Standard Deviation 33.402	5.47 Percent change Standard Deviation 31.992

Adverse Events

Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC

Serious events: 8 serious events

Other events: 26 other events

Deaths: 0 deaths

Bempedoic Acid 180 mg

Serious events: 7 serious events

Other events: 27 other events

Deaths: 0 deaths

Ezetimibe 10 mg

Serious events: 10 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Bempedoic Acid 180 mg + Ezetimibe 10 mg FDC n=107 participants at risk Participants received bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 milligrams (mg)/10 mg tablets orally once daily for 12 weeks.	Bempedoic Acid 180 mg n=110 participants at risk Participants received bempedoic acid 180 mg tablets taken orally once daily for 12 weeks.	Ezetimibe 10 mg n=109 participants at risk Participants received ezetimibe 10 mg overencapsulated tablets orally once daily for 12 weeks.	Placebo n=55 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.93% 1/107 • Up to approximately 14 weeks 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.	1.8% 2/110 • Up to approximately 14 weeks 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.	0.92% 1/109 • Up to approximately 14 weeks 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.	3.6% 2/55 • Up to approximately 14 weeks 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.
Gastrointestinal disorders Constipation	3.7% 4/107 • Up to approximately 14 weeks 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.	0.00% 0/110 • Up to approximately 14 weeks 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.	1.8% 2/109 • Up to approximately 14 weeks 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.	0.00% 0/55 • Up to approximately 14 weeks 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.
Infections and infestations Nasopharyngitis	3.7% 4/107 • Up to approximately 14 weeks 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.	5.5% 6/110 • Up to approximately 14 weeks 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.	3.7% 4/109 • Up to approximately 14 weeks 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.	1.8% 1/55 • Up to approximately 14 weeks 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.
Infections and infestations Urinary tract infection	7.5% 8/107 • Up to approximately 14 weeks 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.	2.7% 3/110 • Up to approximately 14 weeks 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.	2.8% 3/109 • Up to approximately 14 weeks 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.	3.6% 2/55 • Up to approximately 14 weeks 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.
Musculoskeletal and connective tissue disorders Arthralgia	0.93% 1/107 • Up to approximately 14 weeks 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.	3.6% 4/110 • Up to approximately 14 weeks 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.	3.7% 4/109 • Up to approximately 14 weeks 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.	3.6% 2/55 • Up to approximately 14 weeks 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.
Musculoskeletal and connective tissue disorders Back pain	2.8% 3/107 • Up to approximately 14 weeks 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.	2.7% 3/110 • Up to approximately 14 weeks 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.	3.7% 4/109 • Up to approximately 14 weeks 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.	3.6% 2/55 • Up to approximately 14 weeks 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.
Musculoskeletal and connective tissue disorders Muscle spasms	1.9% 2/107 • Up to approximately 14 weeks 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.	0.91% 1/110 • Up to approximately 14 weeks 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.	3.7% 4/109 • Up to approximately 14 weeks 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.	0.00% 0/55 • Up to approximately 14 weeks 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.
Musculoskeletal and connective tissue disorders Myalgia	1.9% 2/107 • Up to approximately 14 weeks 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.	4.5% 5/110 • Up to approximately 14 weeks 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.	1.8% 2/109 • Up to approximately 14 weeks 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.	1.8% 1/55 • Up to approximately 14 weeks 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.
Nervous system disorders Headache	1.9% 2/107 • Up to approximately 14 weeks 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.	3.6% 4/110 • Up to approximately 14 weeks 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.	1.8% 2/109 • Up to approximately 14 weeks 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.	1.8% 1/55 • Up to approximately 14 weeks 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/107 • Up to approximately 14 weeks 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.	0.00% 0/110 • Up to approximately 14 weeks 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.	0.92% 1/109 • Up to approximately 14 weeks 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.	3.6% 2/55 • Up to approximately 14 weeks 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.
Vascular disorders Hypertension	2.8% 3/107 • Up to approximately 14 weeks 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.	4.5% 5/110 • Up to approximately 14 weeks 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.	1.8% 2/109 • Up to approximately 14 weeks 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.	0.00% 0/55 • Up to approximately 14 weeks 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.

Additional Information

Medical Director

Esperion Therapeutics, Inc.

Phone: 1-833-377-7633

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER