Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony)
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
2 other identifiers
interventional
2,230
6 countries
104
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2016
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2016
CompletedStudy Start
First participant enrolled
January 21, 2016
CompletedFirst Posted
Study publicly available on registry
January 28, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 21, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 28, 2018
CompletedResults Posted
Study results publicly available
April 20, 2020
CompletedMay 11, 2020
April 1, 2020
2.1 years
January 20, 2016
March 20, 2020
April 24, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (13)
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported.
Up to approximately 52 weeks
Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event
TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations
TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations).
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) \[AST and (\&)/or ALT \>3 x upper limit of normal (ULN) with concurrent total bilirubin \>2 x ULN\], AST and/or ALT \>3 x ULN, and total bilirubin \>2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. "Repeated and confirmed" was defined as a participant having the last on-study LFT \> x ULN, the last on-treatment LFT \> x ULN, or LFT \> x ULN followed by another LFT \> x ULN.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia
Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the "Overall hypoglycemia AESIs" category; a participant could have been represented in more than one of the individual hypoglycemia AESIs.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis
Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders).
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase \>5 ULN (repeated and confirmed). The percentage of unique participants is reported in the "Overall muscular disorder AESIs" category; a participant could have been represented in more than one of the individual muscular disorder AESIs.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the "Overall neurocognitive disorder AESIs" category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus
Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the "Overall new onset/worsening diabetes mellitus AESIs" category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs.
Up to approximately 52 weeks
Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (ml/min/1.73m\^2), and change from baseline in creatinine \>1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the "Overall renal disorder AESIs" category; a participant could have been represented in more than one of the individual renal disorder AESIs.
Up to approximately 52 weeks
Change From Baseline to Week 52 in Uric Acid (Urate) Level
Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.
Baseline and Week 52
Change From Baseline to Week 52 in Creatinine Level
Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.
Baseline and Week 52
Change From Baseline to Week 52 in Hemoglobin Level
Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.
Baseline and Week 52
Secondary Outcomes (2)
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Baseline; Week 12
Absolute Change From Baseline to Week 12 in LDL-C
Baseline; Week 12
Other Outcomes (15)
Percent Change From Baseline to Week 24 in LDL-C
Baseline; Week 24
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Baseline; Week 12
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Baseline; Week 12
- +12 more other outcomes
Study Arms (2)
ETC-1002
EXPERIMENTALETC-1002 180 mg/day
Placebo
PLACEBO COMPARATORPlacebo control
Interventions
Eligibility Criteria
You may qualify if:
- Fasting LDL-C ≥ 70 mg/dL
- High cardiovascular risk (diagnosis of HeFH or ASCVD)
- Be on maximally tolerated lipid-modifying therapy
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (104)
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Huntsville, Alabama, United States
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Cottonwood, Arizona, United States
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Phoenix, Arizona, United States
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Canoga Park, California, United States
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Santa Rosa, California, United States
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Bridgeport, Connecticut, United States
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Hartford, Connecticut, United States
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Atlantis, Florida, United States
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Boca Raton, Florida, United States
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Crestview, Florida, United States
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Crystal River, Florida, United States
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Daytona Beach, Florida, United States
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Lake Worth, Florida, United States
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Miami Lakes, Florida, United States
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Tampa, Florida, United States
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Park Ridge, Illinois, United States
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Iowa City, Iowa, United States
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Overland Park, Kansas, United States
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Covington, Kentucky, United States
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Louisville, Kentucky, United States
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Minden, Louisiana, United States
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Monroe, Louisiana, United States
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Shreveport, Louisiana, United States
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Auburn, Maine, United States
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Midland, Michigan, United States
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Saginaw, Michigan, United States
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Saint Cloud, Minnesota, United States
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Tupelo, Mississippi, United States
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Jefferson City, Missouri, United States
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Nashua, New Hampshire, United States
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Bridgewater, New Jersey, United States
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Cary, North Carolina, United States
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Mount Airy, North Carolina, United States
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Raleigh, North Carolina, United States
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Rocky Mount, North Carolina, United States
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Wilmington, North Carolina, United States
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Cincinnati, Ohio, United States
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Sandusky, Ohio, United States
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Willoughby, Ohio, United States
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Hillsboro, Oregon, United States
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Fort Worth, Texas, United States
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Katy, Texas, United States
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Kingwood, Texas, United States
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Orem, Utah, United States
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Richmond, Virginia, United States
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Puyallup, Washington, United States
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Tacoma, Washington, United States
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Vancouver, British Columbia, Canada
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Victoria, British Columbia, Canada
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Gatineau, Ontario, Canada
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Mississauga, Ontario, Canada
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Oshawa, Ontario, Canada
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Peterborough, Ontario, Canada
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Scarborough Village, Ontario, Canada
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Chicoutimi, Quebec, Canada
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Gatineau, Quebec, Canada
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Longueuil, Quebec, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Saint-Charles-Borromée, Quebec, Canada
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Saint-Jean-sur-Richelieu, Quebec, Canada
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Berlin, Germany
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Dresden, Germany
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Essen, Germany
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Frankfurt, Germany
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Leipzig, Germany
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München, Germany
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Amsterdam, Netherlands
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Arnhem, Netherlands
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Eindhoven, Netherlands
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Goes, Netherlands
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Groningen, Netherlands
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Hardenberg, Netherlands
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Leiden, Netherlands
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Rotterdam, Netherlands
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Venlo, Netherlands
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Zutphen, Netherlands
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Gdansk, Poland
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Gdynia, Poland
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Katowice, Poland
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Krakow, Poland
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Lodz, Poland
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Lowicz, Poland
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Poznan, Poland
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Puławy, Poland
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Torun, Poland
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Wroclaw, Poland
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Bexhill-on-Sea, United Kingdom
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Birmingham, United Kingdom
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Chichester, United Kingdom
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Chippenham, United Kingdom
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Glasgow, United Kingdom
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Hull, United Kingdom
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Liverpool, United Kingdom
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Reading, United Kingdom
Related Publications (9)
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.
PMID: 27892461BACKGROUNDStone 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.
PMID: 24222016BACKGROUNDGoldberg 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.
PMID: 21600525BACKGROUNDPollex 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.
PMID: 18537526BACKGROUNDSharrett 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.
PMID: 11535564BACKGROUNDRay 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.
PMID: 30865796RESULTRidker PM, Lei L, Ray KK, Ballantyne CM, Bradwin G, Rifai N. Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: A secondary analysis of the CLEAR harmony trial. J Clin Lipidol. 2023 Mar-Apr;17(2):297-302. doi: 10.1016/j.jacl.2023.02.002. Epub 2023 Feb 14.
PMID: 36813656DERIVEDBallantyne 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.
PMID: 35916348DERIVEDBanach 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.
PMID: 32609313DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Esperion Therapeutics, Inc.
Study Officials
- STUDY DIRECTOR
Ron Haberman, MD
Esperion Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2016
First Posted
January 28, 2016
Study Start
January 21, 2016
Primary Completion
February 21, 2018
Study Completion
March 28, 2018
Last Updated
May 11, 2020
Results First Posted
April 20, 2020
Record last verified: 2020-04