Evaluation of ETC-1002 vs Placebo in Patients Receiving Ongoing Statin Therapy

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of ETC-1002 Versus Placebo in Patients With Hypercholesterolemia Receiving Ongoing Statin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072161
• Other study ID #: 1002-009
• Status: Completed
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: January 2015

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 and how ETC-1002 affects the levels of LDL-C (bad cholesterol) in patients receiving ongoing statin therapy.

Description:

Approximately 132 hypercholesterolemic patients already taking statin therapy to treat elevated LDL-C will be randomized in a ratio of 1:1:1 to receive either ETC-1002 (120 mg or 180 mg dose), or placebo for 12 weeks in addition to ongoing statin therapy. This study will explore the safety and efficacy of ETC-1002 when given to patients receiving statin therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Fasting, calculated mean LDL-C =130 mg/dL and =220 mg/dL

• Fasting mean TG level =400 mg/dL

• Stable statin therapy for at least 3 months prior to screening: atorvastatin (10 or 20 mg daily), simvastatin (5, 10 or 20 mg daily), rosuvastatin (5 or 10 mg daily), or pravastatin (10, 20 or 40 mg daily)

Exclusion Criteria:

• Clinically significant cardiovascular disease within 12 months of screening

• Current muscle-related symptoms that may be due to ongoing statin therapy or a history of certain lab abnormalities that occurred during statin therapy and resolved when statin therapy was discontinued

• Type 1 diabetes or uncontrolled type 2 diabetes

• Use of metformin or thiazolidinediones (TZD) within 4 weeks of screening

• History of chronic musculoskeletal symptoms such as fibromyalgia

• Uncontrolled hypothyroidism

• Liver disease or dysfunction

• Renal dysfunction or nephritic syndrome

• Gastrointestinal conditions or procedures or surgeries

• Hematologic or coagulation disorders or low hemoglobin levels

• HIV or AIDS

• History of malignancy

• History of drug or alcohol abuse within 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
ETC-1002 capsules, taken once daily oral
• Placebo
Placebo capsules, taken once daily oral
• Statin Therapy
Patients remained on ongoing statin therapy (not study provided) of either Atorvastatin 10mg or 20mg; Simvastatin 5mg, 10mg or 20mg; Rosuvastatin 5mg or 10mg; or Pravastatin 10mg, 20mg or 40mg.

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
Primary	Percent change from baseline in calculated low density lipoprotein-cholesterol (LDL-C)		12 weeks
Secondary	Percent change in non-high-density lipoprotein cholesterol (non-HDL-C)		12 weeks
Secondary	Percent change in apolipoprotein B (ApoB)		12 weeks
Secondary	Percent change in total cholesterol (TC)		12 weeks
Secondary	Percent change in high-sensitivity C-reactive protein (hsCRP)		12 weeks
Secondary	Percent change in triglycerides (TG)		12 weeks
Secondary	Percent change in lipoprotein particle number		12 weeks
Secondary	Safety using adverse event reports; clinical laboratory results		12 weeks
Secondary	Safety using adverse event reports; vital signs		12 weeks
Secondary	Pharmacokinetic plasma trough concentrations of ETC-1002 and metabolite 15228		12 weeks