Trial Outcomes & Findings for Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension (NCT NCT02178098)

NCT ID: NCT02178098

Last Updated: 2023-04-04

Results Overview

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 143 participants
• Primary outcome timeframe: Baseline; 6 weeks
• Results posted on: 2023-04-04

Participant Flow

Participant milestones

Measure	Placebo Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Overall Study STARTED	72	71
Overall Study COMPLETED	67	59
Overall Study NOT COMPLETED	5	12

Reasons for withdrawal

Measure	Placebo Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Overall Study Withdrawal by Subject	0	6
Overall Study Adverse Event	1	2
Overall Study Protocol Violation	1	1
Overall Study Lost to Follow-up	0	1
Overall Study Sponsor Request	1	0
Overall Study Other	2	2

Baseline Characteristics

Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension

Baseline characteristics by cohort

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=71 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.	Total n=143 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 8.29 • n=5 Participants	54.6 years STANDARD_DEVIATION 8.41 • n=7 Participants	55.6 years STANDARD_DEVIATION 8.38 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	26 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	45 Participants n=7 Participants	82 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized White	45 Participants n=5 Participants	49 Participants n=7 Participants	94 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6	3.16 Percent Change Standard Error 2.133	-21.08 Percent Change Standard Error 2.196

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6	-0.64 millimeters of mercury (mmHg) Standard Error 1.045	-2.28 millimeters of mercury (mmHg) Standard Error 1.085

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6	-0.05 mmHg Standard Deviation 0.760	-1.10 mmHg Standard Deviation 0.790

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Mean Daytime SBP to Week 6	-0.35 mmHg Standard Error 1.198	-2.66 mmHg Standard Error 1.245

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Mean Daytime DBP to Week 6	-0.01 mmHg Standard Error 0.856	-1.47 mmHg Standard Error 0.890

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Mean Nighttime SBP to Week 6	-1.18 mmHg Standard Error 1.167	-1.57 mmHg Standard Error 1.212

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=64 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Mean Nighttime DBP to Week 6	-0.52 mmHg Standard Error 0.879	-0.33 mmHg Standard Error 0.913

SECONDARY outcome

Timeframe: Baseline: 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Sitting Cuff SBP to Week 6	-4.98 mmHg Standard Error 1.274	-3.45 mmHg Standard Error 1.311

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only participants with available data were analyzed.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Sitting Cuff DBP to Week 6	-3.32 mmHg Standard Error 0.820	-2.53 mmHg Standard Error 0.844

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: miTT Population. Only participants with available data were analyzed.

A non-parametric analysis was performed for hsCRP parameters. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the last value prior to the first dose of study medication. If hsCRP was <0.2, 0.1 was imputed for analysis. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=61 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6	19.61 Percent Change Interval -16.67 to 64.29	-25.00 Percent Change Interval -50.85 to 0.0

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Total Cholesterol to Week 6	2.90 Percent Change Standard Error 1.389	-13.77 Percent Change Standard Error 1.430

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=69 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=61 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6	4.77 Percent Change Standard Error 1.797	-14.13 Percent Change Standard Error 1.911

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6	3.20 Percent Change Standard Error 1.728	-15.49 Percent Change Standard Error 1.779

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. Data was analyzed using non-parametric analysis.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Triglycerides (TG) to Week 6	-3.75 Percent Change Interval -18.67 to 15.69	-0.07 Percent Change Interval -20.63 to 36.38

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=72 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=68 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in HDL-C to Week 6	2.42 Percent Change Standard Error 1.614	-5.76 Percent Change Standard Error 1.661

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: mITT Population. Only 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 was defined as the mean of the values from Week -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value.

Outcome measures

Measure	Placebo n=68 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=61 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6	1.08 Percent Change Interval -23.81 to 30.46	9.56 Percent Change Interval -19.49 to 43.53

SECONDARY outcome

Timeframe: Baseline; 6 weeks

Population: Safety Population: all randomized participants who received at least 1 dose of study drug. Only participants with available data were analyzed.

Baseline was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Measure	Placebo n=67 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=57 Participants Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Change From Baseline in Body Weight to Week 6	-0.335 kilograms Standard Deviation 1.590	-0.009 kilograms Standard Deviation 1.927

SECONDARY outcome

Timeframe: Week 2, Week 4 and Week 6

Population: Pharmacokinetic Concentration Population: all randomized participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration value for study drug collected between 18 and 36 hours post-dose. Only participants with available data were analyzed.

Plasma trough concentration is defined as the lowest concentration reached before the next dose is administered.

Outcome measures

Measure	Placebo n=70 Participants Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 2, ETC-1002	6666.20 nanograms per milliliter (ng/mL) Standard Deviation 4777.661	—
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 4, ETC-1002	6817.45 nanograms per milliliter (ng/mL) Standard Deviation 4543.944	—
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 6, ETC-1002	6836.36 nanograms per milliliter (ng/mL) Standard Deviation 3702.241	—
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 2, ESP15228	1219.60 nanograms per milliliter (ng/mL) Standard Deviation 783.00	—
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 4, ESP15228	1220.79 nanograms per milliliter (ng/mL) Standard Deviation 674.437	—
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 Week 6, ESP15228	1221.32 nanograms per milliliter (ng/mL) Standard Deviation 557.930	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

ETC-1002 180 mg

Serious events: 4 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=72 participants at risk Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=71 participants at risk Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Cardiac disorders Acute myocardial infarction	1.4% 1/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	0.00% 0/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial flutter	0.00% 0/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	1.4% 1/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Sinus tachycardia	1.4% 1/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	0.00% 0/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	2.8% 2/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	1.4% 1/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	1.4% 1/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	0.00% 0/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.

Other adverse events

Measure	Placebo n=72 participants at risk Participants received matching oral placebo capsules taken once daily for 6 weeks.	ETC-1002 180 mg n=71 participants at risk Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks.
Nervous system disorders Headache	5.6% 4/72 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.	4.2% 3/71 • Up to approximately 14 weeks The analysis was performed using the Safety Population, which comprised of all randomized participants who received at least 1 dose of study drug.

Additional Information

Medical Director

Esperion Therapeutics, Inc.

Phone: 1-833-377-7633

Email: medinfo@esperion.com

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 the publication be withheld.
• Publication restrictions are in place

Restriction type: OTHER