Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ETC-1002
Ezetimibe
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia focused on measuring Statin intolerant, Statin tolerant, LDL, Cholesterol
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Active Comparator
Experimental
Experimental
Arm Label
ETC-1002 120 mg/day
ETC-1002 180 mg/day
ezetimibe 10mg/day
ETC-1002 120 mg/day + ezetimibe 10mg/day
ETC-1002 180 mg/day + ezetimibe 10mg/day
Arm Description
Orally, once daily in morning as capsules
Orally, once daily in morning as capsules
Orally, once daily in morning as capsules
Orally, once daily in morning
Orally, once daily in morning
Outcomes
Primary Outcome Measures
Percent change in calculated low density lipoprotein-cholesterol (LDL-C)
Secondary Outcome Measures
Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C)
Safety using adverse event reports; vital signs
Percent change in Apolipoprotein B (ApoB)
Percent change in high sensitivity C-reactive protein (hsCRP)
Safety using adverse event reports; clinical laboratory results
Safety using adverse event reports; rates of muscle-related adverse
Full Information
NCT ID
NCT01941836
First Posted
September 6, 2013
Last Updated
March 26, 2019
Sponsor
Esperion Therapeutics, Inc.
Collaborators
Medpace, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01941836
Brief Title
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Esperion Therapeutics, Inc.
Collaborators
Medpace, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
Keywords
Statin intolerant, Statin tolerant, LDL, Cholesterol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
349 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ETC-1002 120 mg/day
Arm Type
Experimental
Arm Description
Orally, once daily in morning as capsules
Arm Title
ETC-1002 180 mg/day
Arm Type
Experimental
Arm Description
Orally, once daily in morning as capsules
Arm Title
ezetimibe 10mg/day
Arm Type
Active Comparator
Arm Description
Orally, once daily in morning as capsules
Arm Title
ETC-1002 120 mg/day + ezetimibe 10mg/day
Arm Type
Experimental
Arm Description
Orally, once daily in morning
Arm Title
ETC-1002 180 mg/day + ezetimibe 10mg/day
Arm Type
Experimental
Arm Description
Orally, once daily in morning
Intervention Type
Drug
Intervention Name(s)
ETC-1002
Intervention Description
Patients receive ETC-1002
Intervention Type
Drug
Intervention Name(s)
Ezetimibe
Other Intervention Name(s)
Zetia
Intervention Description
Patients receive ezetimibe
Primary Outcome Measure Information:
Title
Percent change in calculated low density lipoprotein-cholesterol (LDL-C)
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C)
Time Frame
Baseline and 12 weeks
Title
Safety using adverse event reports; vital signs
Time Frame
up to 21 weeks including screening
Title
Percent change in Apolipoprotein B (ApoB)
Time Frame
Baseline and 12 weeks
Title
Percent change in high sensitivity C-reactive protein (hsCRP)
Time Frame
Baseline and 12 weeks
Title
Safety using adverse event reports; clinical laboratory results
Time Frame
up to 21 weeks including screening
Title
Safety using adverse event reports; rates of muscle-related adverse
Time Frame
up to 21 weeks including screening
Other Pre-specified Outcome Measures:
Title
Pharmacokinetic plasma trough concentrations of ETC-1002 and its metabolite ESP15228
Time Frame
Week 2, Week 4, Week 8 and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diane E MacDougall, MS
Organizational Affiliation
Esperion Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
City
Muscle Shoals
State/Province
Alabama
ZIP/Postal Code
35662
Country
United States
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
City
Chino
State/Province
California
ZIP/Postal Code
91710
Country
United States
City
Lincoln
State/Province
California
ZIP/Postal Code
95821
Country
United States
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90059
Country
United States
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
City
Thousand Oaks
State/Province
California
ZIP/Postal Code
91360
Country
United States
City
Vista
State/Province
California
ZIP/Postal Code
92083
Country
United States
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32223
Country
United States
City
Oviedo
State/Province
Florida
ZIP/Postal Code
32765
Country
United States
City
Ponte Vedra
State/Province
Florida
ZIP/Postal Code
32081
Country
United States
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30066
Country
United States
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83646
Country
United States
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66214
Country
United States
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
City
Clifton
State/Province
New Jersey
ZIP/Postal Code
07012
Country
United States
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
City
New Windsor
State/Province
New York
ZIP/Postal Code
12553
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
26900
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45227
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
City
Franklin
State/Province
Ohio
ZIP/Postal Code
45005
Country
United States
City
Lyndhurst
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
City
Marion
State/Province
Ohio
ZIP/Postal Code
43302
Country
United States
City
Willoughby Hills
State/Province
Ohio
ZIP/Postal Code
44094
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77072
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84124
Country
United States
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States
City
Olympia
State/Province
Washington
ZIP/Postal Code
98502
Country
United States
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23770179
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.
Results Reference
background
PubMed Identifier
23709692
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.
Results Reference
background
PubMed Identifier
23118444
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.
Results Reference
background
PubMed Identifier
24385236
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.
Results Reference
background
PubMed Identifier
27206943
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.
Results Reference
derived
Learn more about this trial
Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients
We'll reach out to this number within 24 hrs