Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension

A Placebo-Controlled, Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ETC-1002 in Patients With Hypercholesterolemia and Hypertension

This Phase 2 study will assess the efficacy and safety of ETC-1002 monotherapy versus placebo in participants with hypercholesterolemia and hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension; Hypercholesterolemia
• Intervention / Treatment: Drug: ETC-1002; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
    • Muscle Shoals, Alabama, United States, 35662
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Glendale, Arizona, United States, 85306
  • California
    • Los Angeles, California, United States, 90057
  • Florida
    • DeLand, Florida, United States, 32720
    • Fort Lauderdale, Florida, United States, 33306
    • Hialeah, Florida, United States, 33012
    • Oviedo, Florida, United States, 32765
    • Pembroke Pines, Florida, United States, 33026
    • Pembroke Pines, Florida, United States, 33029
    • Port Orange, Florida, United States, 32127
  • Idaho
    • Meridian, Idaho, United States, 83646
  • Illinois
    • Chicago, Illinois, United States, 60607
    • Gurnee, Illinois, United States, 60031
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • Kentucky
    • Paducah, Kentucky, United States, 42003
  • Maine
    • Auburn, Maine, United States, 04210
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
  • Montana
    • Butte, Montana, United States, 59701
  • Nevada
    • Las Vegas, Nevada, United States, 89123
  • New Jersey
    • Berlin, New Jersey, United States, 08009
  • New York
    • Endwell, New York, United States, 13760
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cincinnati, Ohio, United States, 45246
    • Cincinnati, Ohio, United States, 45245
    • Lyndhurst, Ohio, United States, 44124
    • Willoughby Hills, Ohio, United States, 44094
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
  • Oregon
    • Eugene, Oregon, United States, 97404
  • Pennsylvania
    • Downingtown, Pennsylvania, United States, 19335
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Site 1
    • Mount Pleasant, South Carolina, United States, 29464
      • Site 2
    • Simpsonville, South Carolina, United States, 29681
  • Texas
    • Corpus Christi, Texas, United States, 78404
    • Dallas, Texas, United States, 75230
    • Dallas, Texas, United States, 75234
    • Houston, Texas, United States, 77036
  • Utah
    • Salt Lake City, Utah, United States, 84107
    • Salt Lake City, Utah, United States, 84124
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
    • Madison, Wisconsin, United States, 53719

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mean 24-hour ambulatory SBP greater than or equal to 130 mmHg
• or- Mean 24-hour ambulatory DBP greater than or equal to 80 mmHg
• Fasting LDL-C between 100 and 220 mg/dL
• Fasting triglycerides less than 400 mg/dL
• Body mass index (BMI) between 18 and 45 kg/m2

Exclusion Criteria:

• Known or suspected secondary hypertension or history of malignant hypertension
• Taking more than two anti-hypertension medications at the first visit
• History or current clinically significant cardiovascular disease
• History or current type 1 diabetes or type 2 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo control	Drug: Placebo; Placebo capsules taken once daily
Experimental: ETC-1002; ETC-1002 180 mg/day	Drug: ETC-1002; ETC-1002 capsules taken once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6	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	Baseline; 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6	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.	Baseline; 6 weeks
Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Mean Daytime SBP to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Mean Daytime DBP to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Mean Nighttime SBP to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Mean Nighttime DBP to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Sitting Cuff SBP to Week 6	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.	Baseline: 6 weeks
Change From Baseline in Sitting Cuff DBP to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in Total Cholesterol to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in Triglycerides (TG) to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in HDL-C to Week 6	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.	Baseline; 6 weeks
Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6	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.	Baseline; 6 weeks
Change From Baseline in Body Weight to Week 6	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.	Baseline; 6 weeks
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228	Plasma trough concentration is defined as the lowest concentration reached before the next dose is administered.	Week 2, Week 4 and Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in non-HDL-C		Baseline to week 6
Percent change in total cholesterol		Baseline to week 6
Percent change in apolipoprotein B (ApoB)		Baseline to week 6
Change in body weight	Kg change in body weight from baseline to week 6	Baseline to week 6
Plasma trough study drug pharmacokinetics	ETC-1002 and ESP15228 trough plasma concentrations	Baseline and week 6

Collaborators and Investigators

• Sponsor: Esperion Therapeutics, Inc.
• Collaborators: Medpace, Inc.
• Investigators: Study Director: Medpace Medical Monitor, Medpace, Inc.

Publications and helpful links

General Publications

• Gutierrez MJ, Rosenberg NL, Macdougall DE, Hanselman JC, Margulies JR, Strange P, Milad MA, McBride SJ, Newton RS. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):676-83. doi: 10.1161/ATVBAHA.113.302677. Epub 2014 Jan 2.
• Ballantyne CM, Davidson MH, Macdougall DE, Bays HE, Dicarlo LA, Rosenberg NL, Margulies J, Newton RS. Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. J Am Coll Cardiol. 2013 Sep 24;62(13):1154-62. doi: 10.1016/j.jacc.2013.05.050. Epub 2013 Jun 13.
• Filippov S, Pinkosky SL, Lister RJ, Pawloski C, Hanselman JC, Cramer CT, Srivastava RAK, Hurley TR, Bradshaw CD, Spahr MA, Newton RS. ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK. J Lipid Res. 2013 Aug;54(8):2095-2108. doi: 10.1194/jlr.M035212. Epub 2013 May 24.
• Pinkosky SL, Filippov S, Srivastava RA, Hanselman JC, Bradshaw CD, Hurley TR, Cramer CT, Spahr MA, Brant AF, Houghton JL, Baker C, Naples M, Adeli K, Newton RS. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res. 2013 Jan;54(1):134-51. doi: 10.1194/jlr.M030528. Epub 2012 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2014
• Primary Completion (Actual): May 22, 2015
• Study Completion (Actual): May 22, 2015

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): June 30, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cholesterol; LDL
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertension; Hypercholesterolemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 1002-014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No