Clinical trial NCT02072161: Evaluation of ETC-1002 vs Placebo in Patients Receiving Ongoing Statin Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: Statin
LDL
Cholesterol
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2014-02-26
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent change from baseline in calculated low density lipoprotein-cholesterol (LDL-C)
timeFrame: 12 weeks
Secondary outcomes:
measure: Percent change in non-high-density lipoprotein cholesterol (non-HDL-C)
timeFrame: 12 weeks
measure: Percent change in apolipoprotein B (ApoB)
timeFrame: 12 weeks
measure: Percent change in total cholesterol (TC)
timeFrame: 12 weeks
measure: Percent change in high-sensitivity C-reactive protein (hsCRP)
timeFrame: 12 weeks
measure: Percent change in triglycerides (TG)
timeFrame: 12 weeks
measure: Percent change in lipoprotein particle number
timeFrame: 12 weeks
measure: Safety using adverse event reports; clinical laboratory results
timeFrame: 12 weeks
measure: Safety using adverse event reports; vital signs
timeFrame: 12 weeks
measure: Pharmacokinetic plasma trough concentrations of ETC-1002 and metabolite 15228
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Chino
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Brandon
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Oviedo
country: United States
state: Florida
city: Ponte Vedra
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Port Gibson
country: United States
state: Mississippi
city: Rochester
country: United States
state: New York
city: Salisbury
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Franklin
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Greer
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Summerville
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Orem
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Diane E MacDougall
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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.
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.