A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides

• Sponsor: Esperion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01262638
• Collaborator: (none)
• Enrollment: 177
• Locations: 11
• Arms: 8
• Duration (Months): 8.7
• Patients Per Site: 16.1
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This Phase 2 proof-of-concept study will assess the lipid regulating efficacy and safety of ETC-1002 in subjects with hypercholesterolemia and either normal or elevated triglycerides.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia	Drug: ETC-1002; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 177 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled, Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of ETC-1002 in Subjects With Hypercholesterolemia and Either Normal or Elevated Triglycerides.
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Aug 23, 2011
• Actual Study Completion Date: Aug 23, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ETC-1002 120 mg (Group 1) Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 80 mg (Group 2) Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 40 mg (Group 3) Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: Placebo (Group 4) Subjects with hypercholesterolemia and normal triglycerides	Drug: Placebo; Placebo daily for 12 weeks
Experimental: ETC-1002 120 mg (Group 5) Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 80 mg (Group 6) Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 40 mg (Group 7) Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: Placebo (Group 8) Subjects with hypercholesterolemia and elevated triglycerides	Drug: Placebo; Placebo daily for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) [Baseline; 12 weeks]

   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).

2. Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum [Baseline; 12 weeks]

   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).

Secondary Outcome Measures

1. Percent Change From Baseline to Week 12 in TG [Baseline; 12 weeks]

   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).

2. Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) [Baseline; 12 weeks]

   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).

3. Percent Change From Baseline to Week 12 in Non-HDL-C [Baseline; 12 weeks]

   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).

4. Percent Change From Baseline to Week 12 in Total Cholesterol (TC) [Baseline; 12 weeks]

   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).

5. Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) [Baseline; 12 weeks]

   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).

6. Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) [Baseline; 12 weeks]

   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).

7. Percent Change From Baseline to Week 12 in Lipoprotein (a) [Baseline; 12 weeks]

   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).

8. Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) [Baseline; 12 weeks]

   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).

9. Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) [Baseline; 12 weeks]

   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).

10. Percent Change From Baseline to Week 12 in Total LDL Particles [Baseline; 12 weeks]

    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).

11. Percent Change From Baseline to Week 12 in Total HDL Particles [Baseline; 12 weeks]

    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).

12. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [up to 12 weeks]

    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.

13. Number of Participants With Clinically Significant Physical Examination Findings [up to 12 weeks]

    Clinical significance was determined by the investigator.

14. Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values [Baseline; up to 12 weeks]

    Clinical importance was determined by the investigator.

15. Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values [Baseline; up to 12 weeks]

    Clinical importance was determined by the investigator.

16. Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 [Week 12]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Major Inclusion Criteria:

• Provision of written informed consent prior to any study-specific procedure

• Fasting LDL-C between 130 and 220 mg/dL following wash-out of all lipid regulating medications and supplements

• Fasting triglyceride <400 mg/dL following wash-out of all lipid regulating medications and supplements

• BMI between 18 and 35 mg/kg2

Major Exclusion Criteria:

• Clinically significant cardiovascular disease, diabetes or uncontrolled hypertension

• Females of child bearing potential (i.e., females who are not surgically sterile or post-menopausal)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chandler	Arizona	United States	85225
2		Greenbrae	California	United States	94904
3		Santa Rosa	California	United States	95405
4		Jacksonville	Florida	United States	32216
5		Chicago	Illinois	United States	60654
6		Iowa City	Iowa	United States	52242
7		Louisville	Kentucky	United States	40213
8		Kalamazoo	Michigan	United States	49007
9		Raleigh	North Carolina	United States	27609
10		Houston	Texas	United States	77030
11		Richmond	Virginia	United States	23294

Sponsors and Collaborators

• Esperion Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Esperion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01262638
• Other Study ID Numbers: ETC-1002-003
• First Posted: Dec 17, 2010
• Last Update Posted: Mar 17, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Dyslipidemias; Hypertriglyceridemia; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Study Results

Participant Flow

Recruitment Details

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

Pre-assignment Detail

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.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Period Title: Overall Study
STARTED	45	44	44	44
COMPLETED	38	38	38	37
NOT COMPLETED	7	6	6	7

Baseline Characteristics

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo	Total
Arm/Group Description	Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.	Total of all reporting groups
Overall Participants	45	44	44	44	177
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.4 (8.66)	58.8 (9.00)	56.7 (9.92)	55.5 (10.40)	57.3 (9.52)
Sex: Female, Male (Count of Participants)
Female	26 57.8%	21 47.7%	19 43.2%	13 29.5%	79 44.6%
Male	19 42.2%	23 52.3%	25 56.8%	31 70.5%	98 55.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 2.3%	0 0%	1 2.3%	2 1.1%
Black or African American	7 15.6%	7 15.9%	2 4.5%	6 13.6%	22 12.4%
White	38 84.4%	36 81.8%	41 93.2%	37 84.1%	152 85.9%
More than one race	0 0%	0 0%	1 2.3%	0 0%	1 0.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Calculated Low-density Lipoprotein Cholesterol (LDL-C) (milligrams per deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	163.1 (24.88)	170.2 (26.23)	165.0 (23.08)	167.4 (22.03)	166.4 (24.05)
LDL-C by Triglyceride (TG) Stratum (mg/dL) [Mean (Standard Deviation) ]
Normal Stratum, TG<150 mg/dL	153.8 (22.06)	164.6 (25.36)	160.2 (17.30)	166.6 (17.87)	161.2 (21.15)
Elevated Stratum, TG≥150 mg/dL	172.9 (24.35)	175.7 (26.46)	169.8 (27.25)	168.2 (25.94)	171.7 (25.73)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Least Squares Mean (Standard Error) [Percent Change]	-17.9 (2.17)	-25.0 (2.12)	-26.6 (2.16)	-2.1 (2.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ETC-1002 40 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-15.7
	Confidence Interval	(2-Sided) 95%; -21.8 to -9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ETC-1002 80 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-22.9
	Confidence Interval	(2-Sided) 95%; -28.9 to -16.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ETC-1002 120 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-24.5
	Confidence Interval	(2-Sided) 95%; -30.5 to -18.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Normal (TG<150 mg/dL)	-17.8 (2.92)	-21.9 (2.73)	-29.2 (2.72)	0.3 (2.89)
Elevated (TG≥150 mg/dL)	-17.8 (3.21)	-28.1 (3.22)	-23.6 (3.37)	-4.5 (3.22)

3. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in TG
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Least Squares Mean (Standard Error) [Percent Change]	-15.1 (4.29)	-10.6 (4.16)	1.1 (4.26)	-1.2 (4.29)

4. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Least Squares Mean (Standard Error) [Percent Change]	7.2 (2.22)	0.9 (2.12)	4.4 (2.16)	2.4 (2.18)

5. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Non-HDL-C
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Least Squares Mean (Standard Error) [Percent Change]	-17.4 (2.01)	-22.7 (1.95)	-23.0 (2.00)	-2.3 (2.00)

6. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	42	44	42	42
Least Squares Mean (Standard Error) [Percent Change]	-11.5 (1.53)	-17.8 (1.50)	-17.1 (1.53)	-1.4 (1.53)

7. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	39	38	39
Least Squares Mean (Standard Error) [Percent Change]	-14.6 (1.83)	-18.4 (1.82)	-22.1 (1.84)	-0.9 (1.83)

8. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	39	38	39
Least Squares Mean (Standard Error) [Percent Change]	2.9 (1.96)	-2.7 (1.95)	0.0 (1.97)	-3.1 (1.95)

9. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Lipoprotein (a)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	39	38	39
Least Squares Mean (Standard Error) [Percent Change]	0.3 (5.20)	7.6 (5.20)	16.2 (5.27)	-2.7 (5.22)

10. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	40	37	40
Least Squares Mean (Standard Error) [Percent Change]	2.5 (6.15)	-14.4 (6.08)	5.3 (6.34)	3.6 (6.09)

11. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP)
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	39	38	39
Least Squares Mean (Standard Error) [Percent Change]	18.4 (42.45)	57.0 (42.44)	48.0 (43.24)	86.6 (42.45)

12. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Total LDL Particles
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available date were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	40	36	40
Least Squares Mean (Standard Error) [Percent Change]	-14.8 (2.26)	-16.3 (2.23)	-20.7 (2.34)	1.9 (2.22)

13. Secondary Outcome

Title	Percent Change From Baseline to Week 12 in Total HDL Particles
Description	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).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	39	40	36	40
Least Squares Mean (Standard Error) [Percent Change]	5.7 (1.78)	3.6 (1.74)	7.3 (1.84)	0.4 (1.75)

14. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	45	44	44	44
Count of Participants [Participants]	34 75.6%	32 72.7%	31 70.5%	33 75%

15. Secondary Outcome

Title	Number of Participants With Clinically Significant Physical Examination Findings
Description	Clinical significance was determined by the investigator.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	45	44	44	44
Count of Participants [Participants]	2 4.4%	2 4.5%	0 0%	2 4.5%

16. Secondary Outcome

Title	Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values
Description	Clinical importance was determined by the investigator.
Time Frame	Baseline; up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	45	44	44	44
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values
Description	Clinical importance was determined by the investigator.
Time Frame	Baseline; up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	45	44	44	44
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12
Description	Laboratory abnormalities are laboratory values that are outside the normal range.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Safety Population. Only participants with available data were analyzed.

Arm/Group Title	ETC-1002 40 mg	ETC-1002 80 mg	ETC-1002 120 mg	Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.	Participants received ETC-1002 80 mg, orally, once daily for 12 weeks..	Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.	Participants received placebo, orally, once daily for 12 weeks.
Measure Participants	45	44	44	44
Alanine aminotransferase	4 8.9%	3 6.8%	3 6.8%	4 9.1%
Aspartate aminotransferase	5 11.1%	6 13.6%	8 18.2%	2 4.5%
Creatine kinase	12 26.7%	8 18.2%	3 6.8%	5 11.4%
Creatinine	1 2.2%	0 0%	1 2.3%	0 0%
Total bilirubin	1 2.2%	1 2.3%	0 0%	1 2.3%
Uric acid	6 13.3%	8 18.2%	6 13.6%	3 6.8%
Hemoglobin	5 11.1%	8 18.2%	4 9.1%	2 4.5%
Leukocytes	3 6.7%	2 4.5%	1 2.3%	1 2.3%

Adverse Events

Time Frame	up to 12 weeks
Adverse Event Reporting Description	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.
Arm/Group Title	ETC-1002 40 mg		ETC-1002 80 mg		ETC-1002 120 mg		Placebo
Arm/Group Description	Participants received ETC-1002 40 mg, orally, once daily for 12 weeks.		Participants received ETC-1002 80 mg, orally, once daily for 12 weeks.		Participants received ETC-1002 120 mg, orally, once daily for 12 weeks.		Participants received placebo, orally, once daily for 12 weeks.
All Cause Mortality
	ETC-1002 40 mg		ETC-1002 80 mg		ETC-1002 120 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/44 (0%)		0/44 (0%)		0/44 (0%)
Serious Adverse Events
	ETC-1002 40 mg		ETC-1002 80 mg		ETC-1002 120 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/44 (0%)		0/44 (0%)		1/44 (2.3%)
General disorders
Chest Pain	0/45 (0%)		0/44 (0%)		0/44 (0%)		1/44 (2.3%)
Other (Not Including Serious) Adverse Events
	ETC-1002 40 mg		ETC-1002 80 mg		ETC-1002 120 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/45 (33.3%)		18/44 (40.9%)		17/44 (38.6%)		17/44 (38.6%)
Gastrointestinal disorders
Diarrhoea	3/45 (6.7%)		3/44 (6.8%)		1/44 (2.3%)		3/44 (6.8%)
Nausea	3/45 (6.7%)		3/44 (6.8%)		4/44 (9.1%)		2/44 (4.5%)
General disorders
Fatigue	3/45 (6.7%)		1/44 (2.3%)		1/44 (2.3%)		1/44 (2.3%)
Infections and infestations
Bronchitis	0/45 (0%)		3/44 (6.8%)		1/44 (2.3%)		1/44 (2.3%)
Urinary Tract Infection	4/45 (8.9%)		1/44 (2.3%)		0/44 (0%)		1/44 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/45 (4.4%)		2/44 (4.5%)		1/44 (2.3%)		6/44 (13.6%)
Myalgia	2/45 (4.4%)		2/44 (4.5%)		3/44 (6.8%)		0/44 (0%)
Pain in Extremity	0/45 (0%)		0/44 (0%)		4/44 (9.1%)		1/44 (2.3%)
Nervous system disorders
Headache	5/45 (11.1%)		5/44 (11.4%)		7/44 (15.9%)		4/44 (9.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/45 (4.4%)		3/44 (6.8%)		1/44 (2.3%)		1/44 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.