Clinical trial NCT02666664: Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony)
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability Study of ETC-1002 in Patients With Hyperlipidemia at High Cardiovascular Risk Who Are Not Adequately Controlled by Their Lipid-Modifying Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Atherosclerotic Cardiovascular Diseases
Keywords: hyperlipidemia
cholesterol
heterozygous familial hypercholesterolemia
atherosclerotic cardiovascular disease
ASCVD
HeFH
LDL
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-28
Enrollment: 2230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if ETC-1002 (bempedoic acid) is safe and well-tolerated versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol that is not adequately controlled by their current therapy.


Eligibility criteria: Inclusion Criteria:

* Fasting LDL-C ≥ 70 mg/dL
* High cardiovascular risk (diagnosis of HeFH or ASCVD)
* Be on maximally tolerated lipid-modifying therapy

Exclusion Criteria:

* Total fasting triglyceride ≥500 mg/dL
* Renal dysfunction or nephrotic syndrome or history of nephritis
* Body Mass Index (BMI) ≥50kg/m2
* Significant cardiovascular disease or cardiovascular event in the past 3 months

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus
timeFrame: Up to approximately 52 weeks
measure: Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder
timeFrame: Up to approximately 52 weeks
measure: Change From Baseline to Week 52 in Uric Acid (Urate) Level
timeFrame: Baseline and Week 52
measure: Change From Baseline to Week 52 in Creatinine Level
timeFrame: Baseline and Week 52
measure: Change From Baseline to Week 52 in Hemoglobin Level
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline; Week 12
measure: Absolute Change From Baseline to Week 12 in LDL-C
timeFrame: Baseline; Week 12
Other outcomes:
measure: Percent Change From Baseline to Week 24 in LDL-C
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 52 in LDL-C
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in Non-HDL-C
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in Non-HDL-C
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in TC
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in TC
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in apoB
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in apoB
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in hsCRP
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in hsCRP
timeFrame: Baseline; Week 52
measure: Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52
timeFrame: Week 12, Week 24, and Week 52
Locations:
city: Huntsville
country: United States
state: Alabama
city: Cottonwood
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Canoga Park
country: United States
state: California
city: Santa Rosa
country: United States
state: California
city: Bridgeport
country: United States
state: Connecticut
city: Hartford
country: United States
state: Connecticut
city: Atlantis
country: United States
state: Florida
city: Boca Raton
country: United States
state: Florida
city: Crestview
country: United States
state: Florida
city: Crystal River
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Lake Worth
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Park Ridge
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Overland Park
country: United States
state: Kansas
city: Covington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Minden
country: United States
state: Louisiana
city: Monroe
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Midland
country: United States
state: Michigan
city: Saginaw
country: United States
state: Michigan
city: Saint Cloud
country: United States
state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Jefferson City
country: United States
state: Missouri
city: Nashua
country: United States
state: New Hampshire
city: Bridgewater
country: United States
state: New Jersey
city: Cary
country: United States
state: North Carolina
city: Mount Airy
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Rocky Mount
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Sandusky
country: United States
state: Ohio
city: Willoughby
country: United States
state: Ohio
city: Hillsboro
country: United States
state: Oregon
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: Kingwood
country: United States
state: Texas
city: Orem
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Puyallup
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Gatineau
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Oshawa
country: Canada
state: Ontario
city: Peterborough
country: Canada
state: Ontario
city: Scarborough
country: Canada
state: Ontario
city: Chicoutimi
country: Canada
state: Quebec
city: Gatineau
country: Canada
state: Quebec
city: Longueuil
country: Canada
state: Quebec
city: Montréal
country: Canada
state: Quebec
city: Québec
country: Canada
state: Quebec
city: Saint-Jean-Sur-Richelieu
country: Canada
state: Quebec
city: St-Charles-Borromee
country: Canada
state: Quebec
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Dresden
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Leipzig
country: Germany
city: Muenchen
country: Germany
city: Amsterdam
country: Netherlands
city: Arnhem
country: Netherlands
city: Eindhoven
country: Netherlands
city: Goes
country: Netherlands
city: Groningen
country: Netherlands
city: Hardenberg
country: Netherlands
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Tilburg
country: Netherlands
city: Venlo
country: Netherlands
city: Zutphen
country: Netherlands
city: Gdansk
country: Poland
city: Gdynia
country: Poland
city: Katowice
country: Poland
city: Kraków
country: Poland
city: Poznań
country: Poland
city: Puławy
country: Poland
city: Toruń
country: Poland
city: Wroclaw
country: Poland
city: Łowicz
country: Poland
city: Łódź
country: Poland
city: Bexhill-on-Sea
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Chesterfield
country: United Kingdom
city: Chichester
country: United Kingdom
city: Chippenham
country: United Kingdom
city: Chorley
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Hexham
country: United Kingdom
city: Hull
country: United Kingdom
city: Ipswich
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
city: Reading
country: United Kingdom
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Ron Haberman, MD
role: STUDY_DIRECTOR
References:
citation: Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.
citation: Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. No abstract available.
citation: Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S1-8. doi: 10.1016/j.jacl.2011.04.003. Epub 2011 Apr 12.
citation: Pollex RL, Joy TR, Hegele RA. Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81. doi: 10.1517/14728214.13.2.363.
citation: Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W; Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001 Sep 4;104(10):1108-13. doi: 10.1161/hc3501.095214.
citation: Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, Robinson PL, Ballantyne CM; CLEAR Harmony Trial. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019 Mar 14;380(11):1022-1032. doi: 10.1056/NEJMoa1803917.
citation: Ballantyne CM, Bays HE, Louie MJ, Smart J, Zhang Y, Ray KK. Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid. J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.
citation: Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Flaim J, Ye Z, Catapano AL. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol. 2020 Oct 1;5(10):1124-1135. doi: 10.1001/jamacardio.2020.2314.