Clinical trial NCT01941836: Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: Statin intolerant
Statin tolerant
LDL
Cholesterol
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2013-09-13
Enrollment: 349
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, 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent change in calculated low density lipoprotein-cholesterol (LDL-C)
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C)
timeFrame: Baseline and 12 weeks
measure: Safety using adverse event reports; vital signs
timeFrame: up to 21 weeks including screening
measure: Percent change in Apolipoprotein B (ApoB)
timeFrame: Baseline and 12 weeks
measure: Percent change in high sensitivity C-reactive protein (hsCRP)
timeFrame: Baseline and 12 weeks
measure: Safety using adverse event reports; clinical laboratory results
timeFrame: up to 21 weeks including screening
measure: Safety using adverse event reports; rates of muscle-related adverse
timeFrame: up to 21 weeks including screening
Other outcomes:
measure: Pharmacokinetic plasma trough concentrations of ETC-1002 and its metabolite ESP15228
timeFrame: Week 2, Week 4, Week 8 and Week 12
Locations:
city: Birmingham
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Chino
country: United States
state: California
city: Lincoln
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Vista
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Atlantis
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Hialeah
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: Port Orange
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Meridian
country: United States
state: Idaho
city: Evansville
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Auburn
country: United States
state: Maine
city: Lincoln
country: United States
state: Nebraska
city: Clifton
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New Windsor
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Williamsville
country: United States
state: New York
city: Greensboro
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Beachwood
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
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: Willoughby Hills
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Mount Pleasant
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Round Rock
country: United States
state: Texas
city: Orem
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Olympia
country: United States
state: Washington
city: Renton
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Diane E MacDougall, MS
role: STUDY_DIRECTOR
References:
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.
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: Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6.