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Trial record 1 of 1 for:    1002-040
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Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients With Hyperlipidemia and High CV Risk (CLEAR Harmony)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02666664
Recruitment Status : Completed
First Posted : January 28, 2016
Results First Posted : April 20, 2020
Last Update Posted : May 11, 2020
Sponsor:
Information provided by (Responsible Party):
Esperion Therapeutics

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Atherosclerotic Cardiovascular Diseases Drug: ETC-1002 Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 21, 2016
Actual Primary Completion Date : February 21, 2018
Actual Study Completion Date : March 28, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ETC-1002
ETC-1002 180 mg/day
Drug: ETC-1002
ETC-1002 180 mg tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
Other Name: bempedoic acid

Placebo Comparator: Placebo
Placebo control
Drug: Placebo
Matching placebo tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)




Primary Outcome Measures :
  1. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 52 weeks ]
    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.

  2. Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event [ Time Frame: Up to approximately 52 weeks ]
    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.

  3. Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations [ Time Frame: Up to approximately 52 weeks ]
    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).

  4. Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders [ Time Frame: Up to approximately 52 weeks ]
    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.

  5. Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia [ Time Frame: Up to approximately 52 weeks ]
    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.

  6. Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis [ Time Frame: Up to approximately 52 weeks ]
    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).

  7. Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder [ Time Frame: Up to approximately 52 weeks ]
    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.

  8. Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder [ Time Frame: Up to approximately 52 weeks ]
    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.

  9. Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus [ Time Frame: Up to approximately 52 weeks ]
    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.

  10. Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder [ Time Frame: Up to approximately 52 weeks ]
    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.

  11. Change From Baseline to Week 52 in Uric Acid (Urate) Level [ Time Frame: Baseline and Week 52 ]
    Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.

  12. Change From Baseline to Week 52 in Creatinine Level [ Time Frame: Baseline and Week 52 ]
    Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.

  13. Change From Baseline to Week 52 in Hemoglobin Level [ Time Frame: Baseline and Week 52 ]
    Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.


Secondary Outcome Measures :
  1. Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Least Square mean= LS mean. Percent change was analyzed using the analysis of covariance (ANCOVA) method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  2. Absolute Change From Baseline to Week 12 in LDL-C [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Absolute change from baseline was calculated as: LDL-C value at Week 12 minus Baseline value. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen.


Other Outcome Measures:
  1. Percent Change From Baseline to Week 24 in LDL-C [ Time Frame: Baseline; Week 24 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  2. Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  3. Percent Change From Baseline to Week 12 in Total Cholesterol (TC) [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  4. Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  5. Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline; Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  6. Percent Change From Baseline to Week 52 in LDL-C [ Time Frame: Baseline; Week 52 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(LDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.

  7. Percent Change From Baseline to Week 24 in Non-HDL-C [ Time Frame: Baseline; Week 24 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  8. Percent Change From Baseline to Week 52 in Non-HDL-C [ Time Frame: Baseline; Week 52 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(non-HDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  9. Percent Change From Baseline to Week 24 in TC [ Time Frame: Baseline; Week 24 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  10. Percent Change From Baseline to Week 52 in TC [ Time Frame: Baseline; Week 52 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: [(TC value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  11. Percent Change From Baseline to Week 24 in apoB [ Time Frame: Baseline; Week 24 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed

  12. Percent Change From Baseline to Week 52 in apoB [ Time Frame: Baseline; Week 52 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(apoB value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  13. Percent Change From Baseline to Week 24 in hsCRP [ Time Frame: Baseline; Week 24 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 24 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  14. Percent Change From Baseline to Week 52 in hsCRP [ Time Frame: Baseline; Week 52 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: [(hsCRP value at Week 52 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.

  15. Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 [ Time Frame: Week 12, Week 24, and Week 52 ]
    The percentage of participants who achieved lowering in lipid values of LDL-C below 70 mg/dL have been reported. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Observed data was used for the analysis, no imputation for the missing data was performed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02666664


Locations
Show Show 104 study locations
Sponsors and Collaborators
Esperion Therapeutics
Investigators
Layout table for investigator information
Study Director: Ron Haberman, MD Esperion Therapeutics
  Study Documents (Full-Text)

Documents provided by Esperion Therapeutics:
Statistical Analysis Plan  [PDF] March 22, 2018
Study Protocol  [PDF] May 10, 2017

Additional Information:
Publications of Results:
Other Publications:
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. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Esperion Therapeutics
ClinicalTrials.gov Identifier: NCT02666664    
Other Study ID Numbers: 1002-040
2015-004136-36 ( EudraCT Number )
First Posted: January 28, 2016    Key Record Dates
Results First Posted: April 20, 2020
Last Update Posted: May 11, 2020
Last Verified: April 2020
Keywords provided by Esperion Therapeutics:
hyperlipidemia
cholesterol
heterozygous familial hypercholesterolemia
atherosclerotic cardiovascular disease
ASCVD
HeFH
LDL
Additional relevant MeSH terms:
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Atherosclerosis
Hypercholesterolemia
Hyperlipidemias
Hyperlipoproteinemias
Cardiovascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs