Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02178098
• Other study ID #: 1002-014
• Status: Completed
• Phase: Phase 2
• Start date: June 16, 2014
• Est. completion date: May 22, 2015

Study information

• Verified date: March 2023
• Source: Esperion Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: May 22, 2015
• Est. primary completion date: May 22, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hypertension

Intervention

Drug:
• ETC-1002
ETC-1002 capsules taken once daily
• Placebo
Placebo capsules taken once daily

Locations

Country	Name	City	State
United States	Site 1	Mount Pleasant	South Carolina
United States	Site 2	Mount Pleasant	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Esperion Therapeutics, Inc.	Medpace, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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