Trial Outcomes & Findings for Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant (NCT NCT02988115)

Last Updated: 2020-04-03

Results Overview

PCFB was calculated as the (\[post-Baseline (BL) value minus the BL value\] divided by the BL value ) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available, that single value was used as BL. PCFB in LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment group and stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing lipid data at Week 12 who were no longer taking study treatment, missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking study treatment, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

345 participants

Primary outcome timeframe

Baseline; Week 12

Results posted on

2020-04-03

Participant Flow

602 participants were screened; out of 602, 345 participants were randomized. 76 participants discontinued investigational medicinal product (IMP), and 18 participants withdrew from the study.

Participant milestones

Participant milestones
Measure	Bempedoic Acid Participants received a bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo Participants received matching oral placebo once a day.
Overall Study STARTED	234	111
Overall Study COMPLETED	220	107
Overall Study NOT COMPLETED	14	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Bempedoic Acid Participants received a bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo Participants received matching oral placebo once a day.
Overall Study Adverse Event	6	1
Overall Study Sponsor Decision	5	2
Overall Study Withdrawal by Subject	1	1
Overall Study Withdrawn by Mistake	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Only those participants with available data were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bempedoic Acid n=234 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=111 Participants Participants received matching oral placebo once a day.	Total n=345 Participants Total of all reporting groups
Age, Continuous	65.2 Years STANDARD_DEVIATION 9.66 • n=234 Participants	65.1 Years STANDARD_DEVIATION 9.21 • n=111 Participants	65.2 Years STANDARD_DEVIATION 9.50 • n=345 Participants
Sex: Female, Male Female	133 Participants n=234 Participants	61 Participants n=111 Participants	194 Participants n=345 Participants
Sex: Female, Male Male	101 Participants n=234 Participants	50 Participants n=111 Participants	151 Participants n=345 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=234 Participants	0 Participants n=111 Participants	1 Participants n=345 Participants
Race (NIH/OMB) Asian	6 Participants n=234 Participants	2 Participants n=111 Participants	8 Participants n=345 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=234 Participants	2 Participants n=111 Participants	2 Participants n=345 Participants
Race (NIH/OMB) Black or African American	16 Participants n=234 Participants	10 Participants n=111 Participants	26 Participants n=345 Participants
Race (NIH/OMB) White	211 Participants n=234 Participants	96 Participants n=111 Participants	307 Participants n=345 Participants
Race (NIH/OMB) More than one race	0 Participants n=234 Participants	1 Participants n=111 Participants	1 Participants n=345 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=234 Participants	0 Participants n=111 Participants	0 Participants n=345 Participants
Baseline LCL-C, Non-HDL-C, TC, HDL-C, and TG Values LDL-C	158.48 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 40.387 • n=234 Participants	155.58 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 38.812 • n=111 Participants	157.55 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 39.854 • n=345 Participants
Baseline LCL-C, Non-HDL-C, TC, HDL-C, and TG Values Non-HDL-C	193.49 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 45.101 • n=234 Participants	190.69 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 43.781 • n=111 Participants	192.59 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 44.637 • n=345 Participants
Baseline LCL-C, Non-HDL-C, TC, HDL-C, and TG Values TC	245.66 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 47.252 • n=234 Participants	241.09 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 44.289 • n=111 Participants	244.19 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 46.304 • n=345 Participants
Baseline LCL-C, Non-HDL-C, TC, HDL-C, and TG Values HDL-C	52.17 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 14.535 • n=234 Participants	50.41 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 14.384 • n=111 Participants	51.60 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 14.489 • n=345 Participants
Baseline LCL-C, Non-HDL-C, TC, HDL-C, and TG Values TG	178.96 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 87.522 • n=234 Participants	186.62 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 96.203 • n=111 Participants	181.42 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 90.336 • n=345 Participants
Baseline Apolipoprotein B (apoB)	141.0 mg/dL STANDARD_DEVIATION 31.64 • n=231 Participants • Only those participants with available data were analyzed.	141.9 mg/dL STANDARD_DEVIATION 30.44 • n=107 Participants • Only those participants with available data were analyzed.	141.3 mg/dL STANDARD_DEVIATION 31.22 • n=338 Participants • Only those participants with available data were analyzed.
Baseline High-Sensitivity C-Reactive Protein (hsCRP) Values	2.920 milligrams per liter (mg/L) n=231 Participants • Only those participants with available data were analyzed.	2.780 milligrams per liter (mg/L) n=106 Participants • Only those participants with available data were analyzed.	2.900 milligrams per liter (mg/L) n=337 Participants • Only those participants with available data were analyzed.

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: The Full Analysis Set (FAS), also known as the intention-to-treat (ITT) set of participants, is defined as all randomized participants. Participants were included in their randomized treatment group, regardless of the treatment they actually received. Only those participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Bempedoic Acid n=224 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=107 Participants Participants received matching oral placebo once a day.
Percent Change From Baseline (PCFB) in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12	-22.58 percent change Standard Error 1.290	-1.17 percent change Standard Error 1.421

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: FAS. Only those participants with available data were analyzed.

PCFB was calculated as the (\[post-BL value minus the BL value\] divided by the BL value ) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available then that single value was used as BL. PCFB in LDL-C was analyzed using ANCOVA, with treatment group and stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing lipid data at Week 12 who were no longer taking study treatment, missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking study treatment, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.

Outcome measures

Outcome measures
Measure	Bempedoic Acid n=217 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=106 Participants Participants received matching oral placebo once a day.
Percent Change From Baseline in LDL-C at Week 24	-21.17 percent change Standard Error 1.411	-2.26 percent change Standard Error 1.552

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only those participants with available data were analyzed.

PCFB was calculated as: (\[post-BL value minus the BL value\] divided by the BL value) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available, that single value was used as BL. apoB and TC BL were defined as the last non-missing value on/prior to Day 1. PCFB was analyzed using ANCOVA, with treatment and group stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing data at Week 12 who were no longer taking study treatment (ST), missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking ST, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.

Outcome measures

Outcome measures
Measure	Bempedoic Acid n=224 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=107 Participants Participants received matching oral placebo once a day.
Percent Change From Baseline in the Lipid Profile at Week 12 non-HDL-C	-18.08 percent change Standard Error 1.114	-0.14 percent change Standard Error 1.169
Percent Change From Baseline in the Lipid Profile at Week 12 TC	-15.37 percent change Standard Error 0.879	-0.61 percent change Standard Error 0.961
Percent Change From Baseline in the Lipid Profile at Week 12 apoB	-14.65 percent change Standard Error 1.080	0.32 percent change Standard Error 1.177

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only those participants with available data were analyzed.

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline for hsCRP is defined as the last non-missing value on or prior to Day 1. Percent change from Baseline in hsCRP, non-parametric (Wilcoxon rank-sum test) analysis with Hodges-Lehmann estimates and confidence interval was performed.

Outcome measures

Outcome measures
Measure	Bempedoic Acid n=218 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=103 Participants Participants received matching oral placebo once a day.
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Week 12	-25.37 percent change Interval -52.75 to 10.78	2.67 percent change Interval -31.07 to 38.04

SECONDARY outcome

Timeframe: Baseline; Week 12; Week 24

Population: FAS. Only those participants with available data were analyzed.

Change from Baseline is calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value ) x 100. Baseline is defined as the mean of the last two non-missing values on or prior to Day 1.

Outcome measures

Outcome measures
Measure	Bempedoic Acid n=224 Participants Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=107 Participants Participants received matching oral placebo once a day.
Absolute Change From Baseline in LDL-C at Week 12 and Week 24 Week 24	-37.0 mg/dL Standard Deviation 35.27	-5.1 mg/dL Standard Deviation 26.50
Absolute Change From Baseline in LDL-C at Week 12 and Week 24 Week 12	-39.3 mg/dL Standard Deviation 33.37	-3.1 mg/dL Standard Deviation 23.66

Adverse Events

Bempedoic Acid

Serious events: 14 serious events

Other events: 88 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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 publication be withheld.
Publication restrictions are in place

Restriction type: OTHER

Measure	Bempedoic Acid n=234 participants at risk Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=111 participants at risk Participants received matching oral placebo once a day.
Cardiac disorders Angina unstable	1.3% 3/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Coronary artery disease	1.3% 3/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Angina pectoris	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Cerebrovascular accident	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Colitis	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Eye disorders Corneal lesion	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Ischaemic stroke	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract infection bacterial	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Myeloproliferative neoplasm	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Myocardial infarction	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
General disorders Non-cardiac chest pain	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Seizure	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Skin and subcutaneous tissue disorders Staphylococcal infection	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Urinary tract infection	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Acute kidney injury	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Aortic aneurysm	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Escherichia pyelonephritis	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Escherichia sepsis	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Nephrolithiasis	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Traumatic intracranial haemorrhage	0.00% 0/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.90% 1/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.

Measure	Bempedoic Acid n=234 participants at risk Participants received bempedoic acid 180 milligram (mg) tablet taken orally once a day.	Placebo n=111 participants at risk Participants received matching oral placebo once a day.
Gastrointestinal disorders Dyspepsia	2.1% 5/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Nausea	1.7% 4/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	2.7% 3/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
General disorders Fatigue	3.4% 8/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	6.3% 7/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Infections and infestations Bronchitis	2.6% 6/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	5.4% 6/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Infections and infestations Nasopharyngitis	1.3% 3/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	4.5% 5/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Infections and infestations Upper respiratory tract infection	0.85% 2/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	2.7% 3/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Infections and infestations Urinary tract infection	3.0% 7/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	8.1% 9/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Investigations Blood creatine phosphokinase increased	2.1% 5/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 14/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	4.5% 5/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Back pain	3.0% 7/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	3.6% 4/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	4.3% 10/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	4.5% 5/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Myalgia	4.7% 11/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	7.2% 8/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.43% 1/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	2.7% 3/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 13/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	3.6% 4/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Dizziness	3.0% 7/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	0.00% 0/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Headache	1.7% 4/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	2.7% 3/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 4/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	2.7% 3/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.
Vascular disorders Hypertension	4.3% 10/234 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.	1.8% 2/111 • Up to 24 weeks plus 30 days Treatment-emergent adverse events (TEAEs), defined as those events that began or worsened after the first dose of IMP until 30 days after the last dose of IMP, were reported for the Safety Population. The Safety Population is defined as all randomized participants who received at least 1 dose of double-blind study medication.