Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients With or Without Statin Intolerance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01941836
• Other study ID #: 1002-008
• Status: Completed
• Phase: Phase 2
• Start date: September 2013
• Est. completion date: November 2014

Study information

• Verified date: March 2019
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to see how ETC-1002 is tolerated in the body, to measure the amount of ETC-1002 in the blood, and to determine how ETC-1002 affects the level of LDL-cholesterol (bad cholesterol) and other markers of health and disease in blood and urine in patients with elevated LDL-cholesterol with or without statin intolerance.

Description:

Hypercholesterolemic patients either with or without a history of statin intolerance (1:1 ratio) will be randomized to receive once daily by mouth capsules containing either ETC-1002, ezetimibe, or ETC-1002 + ezetimibe. This study will explore the safety and efficacy of concomitant administration of ETC-1002 and ezetimibe, while also exploring the effect of ezetimibe on ETC-1002 systemic exposure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 349
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• Statin intolerant and statin tolerant

• Fasting LDL-C between 130 mg/dL and 220 mg/dL

• Fasting triglyceride less than or equal to 400 mg/dL

• Body mass index (BMI) between 18 and 45 kg/m2

Key Exclusion Criteria:

• History or current clinically significant cardiovascular disease

• History or current type 1 diabetes or uncontrolled type 2 diabetes

• Use of metformin or thiazolidinediones (TZD) within 3 months of screening

• History of joint symptoms difficult to differentiate from myalgia

• Uncontrolled hypothyroidism

• Liver disease or dysfunction

• Renal dysfunction or nephritic syndrome

• Gastrointestinal (GI) conditions or prior GI procedures

• HIV or AIDS

• History or malignancy

• History or drug or alcohol abuse within last 2 years

• Use of experimental or investigational drugs within 30 days of screening

• Use of ETC-1002 in a previous clinical study

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• ETC-1002
Patients receive ETC-1002
• Ezetimibe
Patients receive ezetimibe

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Esperion Therapeutics	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 RA, 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):2095-108. 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
Other	Pharmacokinetic plasma trough concentrations of ETC-1002 and its metabolite ESP15228		Week 2, Week 4, Week 8 and Week 12
Primary	Percent change in calculated low density lipoprotein-cholesterol (LDL-C)		Baseline and 12 weeks
Secondary	Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C)		Baseline and 12 weeks
Secondary	Safety using adverse event reports; vital signs		up to 21 weeks including screening
Secondary	Percent change in Apolipoprotein B (ApoB)		Baseline and 12 weeks
Secondary	Percent change in high sensitivity C-reactive protein (hsCRP)		Baseline and 12 weeks
Secondary	Safety using adverse event reports; clinical laboratory results		up to 21 weeks including screening
Secondary	Safety using adverse event reports; rates of muscle-related adverse		up to 21 weeks including screening