Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides (NCT NCT01262638)

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 Weeks -1 and 0. Least square (LS) mean percent change from Baseline to Week 12 was based on an analysis of covariance (ANCOVA) model with effects of treatment and triglyceride (TG) stratum and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

177 participants

Primary outcome timeframe

Baseline; 12 weeks

Results posted on

2021-03-17

Participant Flow

A total of 177 participants were enrolled and treated across 11 study sites in the United States.

During Screening, appropriate participants washed off all lipid-regulating drugs and supplements as necessary for 6 weeks prior to randomization. Participants not taking lipid-regulating medications or supplements for 4 weeks prior to Screening may have combined the S1 and Q1 visits. Participants with hypercholesterolemia were stratified into the normal (\<150 milligrams per deciliter \[mg/dL\]) or elevated (≥150 mg/dL) triglycerides (TG) stratum.

Participant milestones

Participant milestones
Measure	ETC-1002 40 mg Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo Participants received placebo, orally, once daily for 12 weeks.
Overall Study STARTED	45	44	44	44
Overall Study COMPLETED	38	38	38	37
Overall Study NOT COMPLETED	7	6	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	ETC-1002 40 mg Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo Participants received placebo, orally, once daily for 12 weeks.
Overall Study Adverse Event	3	4	3	4
Overall Study Protocol Violation	1	0	0	1
Overall Study Withdrawal by Subject	2	1	0	1
Overall Study Per Investigator/Sponsor/Regulatory Body	0	0	1	0
Overall Study Lost to Follow-up	1	1	1	1
Overall Study Participant Went Out of Town	0	0	1	0

Baseline Characteristics

The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.	Total n=177 Participants Total of all reporting groups
Age, Continuous	58.4 Years STANDARD_DEVIATION 8.66 • n=45 Participants	58.8 Years STANDARD_DEVIATION 9.00 • n=44 Participants	56.7 Years STANDARD_DEVIATION 9.92 • n=44 Participants	55.5 Years STANDARD_DEVIATION 10.40 • n=44 Participants	57.3 Years STANDARD_DEVIATION 9.52 • n=177 Participants
Sex: Female, Male Female	26 Participants n=45 Participants	21 Participants n=44 Participants	19 Participants n=44 Participants	13 Participants n=44 Participants	79 Participants n=177 Participants
Sex: Female, Male Male	19 Participants n=45 Participants	23 Participants n=44 Participants	25 Participants n=44 Participants	31 Participants n=44 Participants	98 Participants n=177 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=45 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=177 Participants
Race (NIH/OMB) Asian	0 Participants n=45 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=177 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=45 Participants	1 Participants n=44 Participants	0 Participants n=44 Participants	1 Participants n=44 Participants	2 Participants n=177 Participants
Race (NIH/OMB) Black or African American	7 Participants n=45 Participants	7 Participants n=44 Participants	2 Participants n=44 Participants	6 Participants n=44 Participants	22 Participants n=177 Participants
Race (NIH/OMB) White	38 Participants n=45 Participants	36 Participants n=44 Participants	41 Participants n=44 Participants	37 Participants n=44 Participants	152 Participants n=177 Participants
Race (NIH/OMB) More than one race	0 Participants n=45 Participants	0 Participants n=44 Participants	1 Participants n=44 Participants	0 Participants n=44 Participants	1 Participants n=177 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=45 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=44 Participants	0 Participants n=177 Participants
Calculated Low-density Lipoprotein Cholesterol (LDL-C)	163.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.88 • n=45 Participants	170.2 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.23 • n=44 Participants	165.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 23.08 • n=44 Participants	167.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 22.03 • n=44 Participants	166.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.05 • n=177 Participants
LDL-C by Triglyceride (TG) Stratum Normal Stratum, TG<150 mg/dL	153.8 mg/dL STANDARD_DEVIATION 22.06 • n=23 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	164.6 mg/dL STANDARD_DEVIATION 25.36 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	160.2 mg/dL STANDARD_DEVIATION 17.30 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	166.6 mg/dL STANDARD_DEVIATION 17.87 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	161.2 mg/dL STANDARD_DEVIATION 21.15 • n=89 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.
LDL-C by Triglyceride (TG) Stratum Elevated Stratum, TG≥150 mg/dL	172.9 mg/dL STANDARD_DEVIATION 24.35 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	175.7 mg/dL STANDARD_DEVIATION 26.46 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	169.8 mg/dL STANDARD_DEVIATION 27.25 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	168.2 mg/dL STANDARD_DEVIATION 25.94 • n=22 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.	171.7 mg/dL STANDARD_DEVIATION 25.73 • n=88 Participants • The Overall Number of Baseline Participants analyzed is the sum of the participants in the Normal Stratum and Elevated Stratum.

PRIMARY outcome

Timeframe: Baseline; 12 weeks

Population: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least 1 dose of study medication and had a Baseline assessment and at least 1 post-Baseline assessment, excluding any assessments taken more than 2 days after a dose of study medication

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 Weeks -1 and 0. Least square (LS) mean percent change from Baseline to Week 12 was based on an analysis of covariance (ANCOVA) model with effects of treatment and triglyceride (TG) stratum and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C)	-17.9 Percent Change Standard Error 2.17	-25.0 Percent Change Standard Error 2.12	-26.6 Percent Change Standard Error 2.16	-2.1 Percent Change Standard Error 2.16

PRIMARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population

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 Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and center and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum Normal (TG<150 mg/dL)	-17.8 Percent Change Standard Error 2.92	-21.9 Percent Change Standard Error 2.73	-29.2 Percent Change Standard Error 2.72	0.3 Percent Change Standard Error 2.89
Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum Elevated (TG≥150 mg/dL)	-17.8 Percent Change Standard Error 3.21	-28.1 Percent Change Standard Error 3.22	-23.6 Percent Change Standard Error 3.37	-4.5 Percent Change Standard Error 3.22

SECONDARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population

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 Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TG values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in TG	-15.1 Percent Change Standard Error 4.29	-10.6 Percent Change Standard Error 4.16	1.1 Percent Change Standard Error 4.26	-1.2 Percent Change Standard Error 4.29

SECONDARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population

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 Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C)	7.2 Percent Change Standard Error 2.22	0.9 Percent Change Standard Error 2.12	4.4 Percent Change Standard Error 2.16	2.4 Percent Change Standard Error 2.18

SECONDARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population

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 Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing non-HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Non-HDL-C	-17.4 Percent Change Standard Error 2.01	-22.7 Percent Change Standard Error 1.95	-23.0 Percent Change Standard Error 2.00	-2.3 Percent Change Standard Error 2.00

SECONDARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population

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 Weeks -1 and 0. LS mean percent change from Baseline to Week 12 based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TC values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=42 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=42 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=42 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	-11.5 Percent Change Standard Error 1.53	-17.8 Percent Change Standard Error 1.50	-17.1 Percent Change Standard Error 1.53	-1.4 Percent Change Standard Error 1.53

SECONDARY outcome

Timeframe: Baseline; 12 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 value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoB values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=39 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=38 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=39 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)	-14.6 Percent Change Standard Error 1.83	-18.4 Percent Change Standard Error 1.82	-22.1 Percent Change Standard Error 1.84	-0.9 Percent Change Standard Error 1.83

SECONDARY outcome

Timeframe: Baseline; 12 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 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoAI values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=39 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=38 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=39 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI)	2.9 Percent Change Standard Error 1.96	-2.7 Percent Change Standard Error 1.95	0.0 Percent Change Standard Error 1.97	-3.1 Percent Change Standard Error 1.95

SECONDARY outcome

Timeframe: Baseline; 12 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 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing Lipoprotein (a) values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=39 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=38 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=39 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Lipoprotein (a)	0.3 Percent Change Standard Error 5.20	7.6 Percent Change Standard Error 5.20	16.2 Percent Change Standard Error 5.27	-2.7 Percent Change Standard Error 5.22

SECONDARY outcome

Timeframe: Baseline; 12 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 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing FFA values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=40 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=37 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=40 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA)	2.5 Percent Change Standard Error 6.15	-14.4 Percent Change Standard Error 6.08	5.3 Percent Change Standard Error 6.34	3.6 Percent Change Standard Error 6.09

SECONDARY outcome

Timeframe: Baseline; 12 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 value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing hsCRP values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=39 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=38 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=39 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP)	18.4 Percent Change Standard Error 42.45	57.0 Percent Change Standard Error 42.44	48.0 Percent Change Standard Error 43.24	86.6 Percent Change Standard Error 42.45

SECONDARY outcome

Timeframe: Baseline; 12 weeks

Population: mITT Population. Only participants with available date 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 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=40 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=36 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=40 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Total LDL Particles	-14.8 Percent Change Standard Error 2.26	-16.3 Percent Change Standard Error 2.23	-20.7 Percent Change Standard Error 2.34	1.9 Percent Change Standard Error 2.22

SECONDARY outcome

Timeframe: Baseline; 12 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 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=39 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=40 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=36 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=40 Participants Participants received placebo, orally, once daily for 12 weeks.
Percent Change From Baseline to Week 12 in Total HDL Particles	5.7 Percent Change Standard Error 1.78	3.6 Percent Change Standard Error 1.74	7.3 Percent Change Standard Error 1.84	0.4 Percent Change Standard Error 1.75

SECONDARY outcome

Timeframe: up to 12 weeks

Population: Safety Population: all randomized participants who received at least 1 dose of study medication

TEAEs were defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication.

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	34 Participants	32 Participants	31 Participants	33 Participants

SECONDARY outcome

Timeframe: up to 12 weeks

Population: Safety Population

Clinical significance was determined by the investigator.

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.
Number of Participants With Clinically Significant Physical Examination Findings	2 Participants	2 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline; up to 12 weeks

Population: Safety Population

Clinical importance was determined by the investigator.

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.
Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; up to 12 weeks

Population: Safety Population

Clinical importance was determined by the investigator.

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.
Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 12

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

Laboratory abnormalities are laboratory values that are outside the normal range.

Outcome measures

Outcome measures
Measure	ETC-1002 40 mg n=45 Participants Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 Participants Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 Participants Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 Participants Participants received placebo, orally, once daily for 12 weeks.
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Alanine aminotransferase	4 Participants	3 Participants	3 Participants	4 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Aspartate aminotransferase	5 Participants	6 Participants	8 Participants	2 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Creatinine	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Total bilirubin	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Uric acid	6 Participants	8 Participants	6 Participants	3 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Hemoglobin	5 Participants	8 Participants	4 Participants	2 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Leukocytes	3 Participants	2 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Creatine kinase	12 Participants	8 Participants	3 Participants	5 Participants

Adverse Events

ETC-1002 40 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

ETC-1002 80 mg

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

ETC-1002 120 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ETC-1002 40 mg n=45 participants at risk Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 participants at risk Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 participants at risk Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 participants at risk Participants received placebo, orally, once daily for 12 weeks.
General disorders Chest Pain	0.00% 0/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	0.00% 0/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	0.00% 0/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.

Other adverse events

Other adverse events
Measure	ETC-1002 40 mg n=45 participants at risk Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	ETC-1002 80 mg n=44 participants at risk Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	ETC-1002 120 mg n=44 participants at risk Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Placebo n=44 participants at risk Participants received placebo, orally, once daily for 12 weeks.
Gastrointestinal disorders Nausea	6.7% 3/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	9.1% 4/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	4.5% 2/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	6.7% 3/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
General disorders Fatigue	6.7% 3/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Infections and infestations Bronchitis	0.00% 0/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Infections and infestations Urinary Tract Infection	8.9% 4/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	0.00% 0/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 2/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	4.5% 2/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	13.6% 6/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	4.4% 2/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	4.5% 2/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	0.00% 0/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	0.00% 0/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	9.1% 4/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Headache	11.1% 5/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	11.4% 5/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	15.9% 7/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	9.1% 4/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 2/45 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	6.8% 3/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.	2.3% 1/44 • up to 12 weeks Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication, are reported. The analysis was performed using the Safety Population, comprised of all randomized participants who received at least 1 dose of study medication.

Additional Information

Medical Director

Esperion Therapeutics, Inc.

Phone: 1-833-377-7633

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place