Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients with Hyperlipidemia at High Cardiovascular Risk Not Adequately Controlled by Their Lipid-Modifying Therapy

    Summary
    EudraCT number
    		 2016-003486-26
    Trial protocol
    		 DE   GB  
    Global end of trial date
    22 Sep 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Oct 2019
    First version publication date
    09 Oct 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1002-047
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02991118
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Esperion Therapeutics Inc.
    Sponsor organisation address
    3891 Ranchero Drive, Suite 150, Ann Arbor, Michigan, United States, 48108
    Public contact
    Director of Clinical Development, Esperion Therapeutics Inc., 00 1 7348873903, clinicaltrials@esperion.com
    Scientific contact
    Director of Clinical Development, Esperion Therapeutics Inc., 00 1 7348873903, clinicaltrials@esperion.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Sep 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to assess the 12-week efficacy of bempedoic acid (ETC-1002) 180 milligrams (mg) per day versus placebo in decreasing low-density lipoprotein cholesterol (LDL-C) in high cardiovascular (CV) risk participants with hyperlipidemia (with underlying heterozygous familial hypercholesterolemia [HeFH] and/or atherosclerotic cardiovascular diseases [ASCVD]) who were not adequately controlled with their maximally tolerated lipid-modifying therapy.
    Protection of trial subjects
    This trial was designed, conducted, and monitored in accordance with Sponsor procedures, which comply with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.
    Background therapy
    		 Participants were required to be on stable background lipid-modifying therapy (LMT), including a maximally tolerated statin, for at least 4 weeks prior to screening. Maximally tolerated statins included statin regimens other than daily dosing, including no to very low doses, but reasons for not using high-intensity statin dosing must have been documented. Stable LMT included, but was not limited to, monotherapies or combination therapies containing the following compounds: Statins (Atorvastatin [Lipitor®, Sortis®], Fluvastatin [Lescol®], Lovastatin [Mevacor®, Altoprev™], Pravastatin [Pravachol®], Pitavastatin [Livalo®, Lipostat®], Rosuvastatin [Crestor®], or Simvastatin [Zocor®] at average daily doses <40 mg); selective cholesterol and/or bile acid absorption inhibitors (Cholestyramine/Colestyramine [Questran®, Questran Light®, Prevalite®, Locholest®, Locholest® Light], Colestipol [Colestid®], Colesevelam hydrochloride [Welchol®, Cholestagel®], or Ezetimibe [Zetia®, Ezetrol®]); Fibrates (must have been stable at least 6 weeks prior to screening) (Fenofibrate [Antara®, Lofibra®, Tricor®, Triglide™, Lipantil®, Supralip®], Bezafibrate [Bezalip®], or Ciprofibrate [Modalim®]); PCSK9 inhibitors (Alirocumab [Praluent®], Evolocumab [Repatha®]); Other (Ezetimibe/simvastatin combinations where simvastatin doses were <40 mg/day [Vytorin® 10 mg/10 mg and 10 mg/20 mg, Inegy® 10 mg/20 mg], Atorvastatin/ezetimibe combinations [Atozet®]). An adjunctive therapy plan was in place for those participants whose low-density lipoprotein cholesterol (LDL-C) values met protocol-defined LDL-C threshold criteria. Post-randomization, LDL-C results were masked to investigators to ensure the blind was maintained; however, previously defined thresholds were set to notify investigators and provide an opportunity to adjust the participant’s standard of care regimen.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Nov 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 237
    Country: Number of subjects enrolled
    United Kingdom: 119
    Country: Number of subjects enrolled
    Germany: 78
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    Ukraine: 118
    Country: Number of subjects enrolled
    United States: 213
    Worldwide total number of subjects
    779
    EEA total number of subjects
    434
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    379
    From 65 to 84 years
    395
    85 years and over
    5

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 779 participants were randomized 2:1 to receive either bempedoic acid or placebo.

    Pre-assignment
    Screening details
    		 The study consisted of 3 periods: a 1-week screening period; a 4-week single-blind, placebo run-in period; and a 52-week double-blind, randomized treatment period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The Sponsor, all clinical site personnel (e.g., investigator, pharmacist), and other vendor personnel were blinded to the treatment group for each participant. Participants were also blinded to the treatment they received. Blinding of treatment was required to be maintained for all participants unless, in the opinion of the investigator, the safety of the participant might be at risk.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received placebo once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    -
    Other name
    -
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a placebo tablet once daily by mouth for 52 weeks during the double-blind treatment period.

    Arm title
    		 Bempedoic acid
    Arm description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received a bempedoic acid 180 milligram (mg) tablet once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    bempedoic acid
    Investigational medicinal product code
    ETC-1002
    Other name
    -
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a bempedoic acid 180 mg tablet once daily by mouth for 52 weeks during the double-blind treatment period.

    Number of subjects in period 1
    		Placebo Bempedoic acid
    Started
    257
    522
    Completed
    250
    490
    Not completed
    7
    32
         Consent withdrawn by subject
    1
    7
         Physician decision
    -
    1
         Adverse event, non-fatal
    2
    2
         Death
    3
    8
         Could not attend study visits
    -
    1
         Lost to follow-up
    1
    9
         Moved out of the country
    -
    1
         Protocol deviation
    -
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received placebo once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Reporting group title
    Bempedoic acid
    Reporting group description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received a bempedoic acid 180 milligram (mg) tablet once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Reporting group values
    		 Placebo Bempedoic acid Total
    Number of subjects
    		 257 522 779
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.7 ± 8.73 64.1 ± 8.82 -
    Gender categorical
    Units: Subjects
        Female
    		 89 194 283
        Male
    		 168 328 496
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 0 4 4
        Black or African American
    		 12 24 36
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        White
    		 244 491 735
        Multiple
    		 0 2 2
    Mean low-density lipoprotein cholesterol (LDL-C)
    Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1.
    Units: milligrams per deciliter (mg/dL)
        arithmetic mean (standard deviation)
    		 122.4 ± 38.30 119.4 ± 37.75 -
    Mean non-high-density lipoprotein cholesterol (non-HDL-C)
    Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 153.7 ± 44.36 150.7 ± 42.75 -
    Mean total cholesterol (TC)
    Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 204.8 ± 46.06 202.1 ± 42.71 -
    Mean apolipoprotein B (apoB)
    Baseline was defined as the last non-missing value on or prior to Day 1.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 118.6 ± 30.53 116.2 ± 29.58 -
    Mean high-sensitivity C-reactive protein (hsCRP)
    Baseline was defined as the last non-missing value on or prior to Day 1. Dispersion data are reported as the first quartile and third quartile values.
    Units: milligrams per Liter
        median (inter-quartile range (Q1-Q3))
    		 1.880 (0.920 to 3.790) 1.610 (0.870 to 3.455) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received placebo once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Reporting group title
    Bempedoic acid
    Reporting group description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received a bempedoic acid 180 milligram (mg) tablet once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Primary: Percent change from baseline to Week 12 in low-density lipoprotein cholesterol (LDL-C)

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 12 in low-density lipoprotein cholesterol (LDL-C)
    End point description
    Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants.
    End point type
    Primary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    253 [1]
    498 [2]
    Units: percent change
        least squares mean (standard error)
    2.35 ± 1.446
    -15.07 ± 1.073
    Notes
    [1] - Full Analysis Set. Only those participants with available data were analyzed.
    [2] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Difference [bempedoic acid - placebo] in LS mean
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a confidence interval (CI) of 95%. Data were analyzed using analysis of covariance (ANCOVA), with treatment group and randomization stratification factors (cardiovascular risk and Baseline statin intensity) as factors and Baseline LDL-C as a covariate.
    Comparison groups
    Bempedoic acid v Placebo
    Number of subjects included in analysis
    751
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -17.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.951
         upper limit
    		 -13.896
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.8

    Secondary: Percent change from baseline to Week 24 in LDL-C

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 24 in LDL-C
    End point description
    Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 24
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    247 [3]
    485 [4]
    Units: percent change
        least squares mean (standard error)
    2.66 ± 1.910
    -12.10 ± 1.479
    Notes
    [3] - Full Analysis Set. Only those participants with available data were analyzed.
    [4] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Difference [bempedoic acid - placebo] in LS mean
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a CI of 95%. Data were analyzed using ANCOVA, with treatment group and randomization stratification factors (cardiovascular risk and Baseline statin intensity) as factors and Baseline LDL-C as a covariate. Secondary endpoints were tested in a hierarchical analysis in the order they appear in this summary. Statistical significance at each step was required in order to test the next hypothesis.
    Comparison groups
    Placebo v Bempedoic acid
    Number of subjects included in analysis
    732
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -14.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.504
         upper limit
    		 -10.027
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.418

    Secondary: Percent change from baseline to Week 12 in non-high-density lipoprotein cholesterol (non-HDL-C)

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 12 in non-high-density lipoprotein cholesterol (non-HDL-C)
    End point description
    Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    253 [5]
    498 [6]
    Units: percent change
        least squares mean (standard error)
    2.28 ± 1.351
    -10.75 ± 0.952
    Notes
    [5] - Full Analysis Set. Only those participants with available data were analyzed.
    [6] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Difference [bempedoic acid - placebo] in LS mean
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a CI of 95%. Data were analyzed using ANCOVA, with treatment group and randomization stratification factors (cardiovascular risk and Baseline statin intensity) as factors and Baseline non-HDL-C as a covariate. Secondary endpoints were tested in a hierarchical analysis in the order they appear in this summary. Statistical significance at each step was required in order to test the next hypothesis.
    Comparison groups
    Placebo v Bempedoic acid
    Number of subjects included in analysis
    751
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -13.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.27
         upper limit
    		 -9.794
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.652

    Secondary: Percent change from baseline to Week 12 in total cholesterol (TC)

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 12 in total cholesterol (TC)
    End point description
    Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    253 [7]
    499 [8]
    Units: percent change
        least squares mean (standard error)
    1.26 ± 1.010
    -9.94 ± 0.688
    Notes
    [7] - Full Analysis Set. Only those participants with available data were analyzed.
    [8] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Difference [bempedoic acid - placebo] in LS mean
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a CI of 95%. Data were analyzed using ANCOVA, with treatment group and randomization stratification factors (cardiovascular risk and Baseline statin intensity) as factors and Baseline TC as a covariate. Secondary endpoints were tested in a hierarchical analysis in the order they appear in this summary. Statistical significance at each step was required in order to test the next hypothesis.
    Comparison groups
    Placebo v Bempedoic acid
    Number of subjects included in analysis
    752
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.599
         upper limit
    		 -8.801
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.224

    Secondary: Percent change from baseline to Week 12 in apolipoprotein b (apo B)

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 12 in apolipoprotein b (apo B)
    End point description
    Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    245 [9]
    479 [10]
    Units: percent change
        least squares mean (standard error)
    3.73 ± 1.340
    -9.29 ± 0.851
    Notes
    [9] - Full Analysis Set. Only those participants with available data were analyzed.
    [10] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Difference [bempedoic acid - placebo] in LS mean
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a CI of 95%. Data were analyzed using ANCOVA, with treatment group and randomization stratification factors (cardiovascular risk and Baseline statin intensity) as factors and Baseline apo B as a covariate. Secondary endpoints were tested in a hierarchical analysis in the order they appear in this summary. Statistical significance at each step was required in order to test the next hypothesis.
    Comparison groups
    Placebo v Bempedoic acid
    Number of subjects included in analysis
    724
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -13.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.13
         upper limit
    		 -9.907
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.587

    Secondary: Percent change from baseline to Week 12 in high-sensitivity c-reactive protein (hsCRP)

    		 Close Top of page
    End point title
    		 Percent change from baseline to Week 12 in high-sensitivity c-reactive protein (hsCRP)
    End point description
    Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. The Full Analysis Set was comprised of all randomized participants. The Q3 value reported represents the actual interquartile range (calculated as the third quartile [Q3] value minus the first quartile [Q1] value). -99999 is a null value and serves as a placeholder.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    240 [11]
    467 [12]
    Units: percent change
        median (inter-quartile range (Q1-Q3))
    -9.366 (-99999 to 71.561)
    -18.699 (-99999 to 69.931)
    Notes
    [11] - Full Analysis Set. Only those participants with available data were analyzed.
    [12] - Full Analysis Set. Only those participants with available data were analyzed.
    Statistical analysis title
    		 Wilcoxon Two Sample Test
    Statistical analysis description
    The analysis compared treatment groups using a two-sided test at the 0.05 level of significance and a CI of 95%. A non‐parametric (Wilcoxon rank-sum test) analysis with Hodges-Lehmann estimates and confidence interval was performed. Secondary endpoints were tested in a hierarchical analysis in the order they appear in this summary. Statistical significance at each step was required in order to test the next hypothesis.
    Comparison groups
    Placebo v Bempedoic acid
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.039
    Method
    		 Wilcoxon Two Sample Test
    Parameter type
    		 Location shift
    Point estimate
    -8.733
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.238
         upper limit
    		 -0.434

    Secondary: Change from baseline to Week 12 in LDL-C

    		 Close Top of page
    End point title
    		 Change from baseline to Week 12 in LDL-C
    End point description
    Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. The Full Analysis Set was comprised of all randomized participants. Analysis was conducted using descriptive statistics by treatment group using observed data.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 12
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    253 [13]
    498 [14]
    Units: mg/dL
        arithmetic mean (standard deviation)
    0.0 ± 30.62
    -21.2 ± 30.82
    Notes
    [13] - Full Analysis Set. Only those participants with available data were analyzed.
    [14] - Full Analysis Set. Only those participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 24 in LDL-C

    		 Close Top of page
    End point title
    		 Change from baseline to Week 24 in LDL-C
    End point description
    Baseline was defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. The Full Analysis Set was comprised of all randomized participants. Analysis was conducted using descriptive statistics by treatment group using observed data.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 24
    End point values
    		 Placebo Bempedoic acid
    Number of subjects analysed
    247 [15]
    485 [16]
    Units: mg/dL
        arithmetic mean (standard deviation)
    -1.0 ± 37.51
    -18.7 ± 35.76
    Notes
    [15] - Full Analysis Set. Only those participants with available data were analyzed.
    [16] - Full Analysis Set. Only those participants with available data were analyzed.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    up to Week 52
    Adverse event reporting additional description
    Treatment-emergent events, defined as those adverse events that began or worsened after the first dose of investigational medicinal product (IMP) until 30 days after the last dose of IMP, were collected and reported. The analysis was performed using the Safety Analysis Set, comprised of all randomized participants who received >=1 dose of IMP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received placebo once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Reporting group title
    Bempedoic acid
    Reporting group description
    		 Participants received a placebo tablet once daily by mouth for 4 weeks prior to the 52-week double-blind treatment period. During the treatment period, participants received a bempedoic acid 180 milligram (mg) tablet once daily by mouth for 52 weeks. Participants remained on ongoing lipid-modifying therapy (not study provided) throughout the study.

    Serious adverse events
    		 Placebo Bempedoic acid
    Total subjects affected by serious adverse events
         subjects affected / exposed
    48 / 257 (18.68%)
    106 / 522 (20.31%)
         number of deaths (all causes)
    2
    6
         number of deaths resulting from adverse events
    2
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour of the lung
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 257 (0.39%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery thrombosis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Supportive care
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Exercise tolerance decreased
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 257 (0.78%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent occlusion
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 257 (1.56%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery restenosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gas poisoning
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Kidney rupture
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 257 (0.00%)
    3 / 522 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    3 / 257 (1.17%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 257 (0.39%)
    12 / 522 (2.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    6 / 257 (2.33%)
    9 / 522 (1.72%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    1 / 257 (0.39%)
    4 / 522 (0.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 257 (0.78%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 257 (0.39%)
    4 / 522 (0.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    6 / 257 (2.33%)
    7 / 522 (1.34%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 257 (0.78%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    4 / 257 (1.56%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyporeflexia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 257 (0.78%)
    4 / 522 (0.77%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post stroke epilepsy
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 257 (0.00%)
    4 / 522 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Microcytic anaemia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric antral vascular ectasia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal adhesions
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 257 (0.39%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perinephritis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 257 (0.78%)
    5 / 522 (0.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periostitis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 257 (0.39%)
    2 / 522 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urethral stricture post infection
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 257 (0.00%)
    3 / 522 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 522 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 522 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Bempedoic acid
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    88 / 257 (34.24%)
    211 / 522 (40.42%)
    Investigations
    Blood uric acid increased
         subjects affected / exposed
    1 / 257 (0.39%)
    14 / 522 (2.68%)
         occurrences all number
    1
    14
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 257 (2.33%)
    7 / 522 (1.34%)
         occurrences all number
    6
    7
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 257 (3.50%)
    8 / 522 (1.53%)
         occurrences all number
    9
    10
    Headache
         subjects affected / exposed
    7 / 257 (2.72%)
    10 / 522 (1.92%)
         occurrences all number
    7
    12
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 257 (1.17%)
    14 / 522 (2.68%)
         occurrences all number
    3
    15
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    9 / 257 (3.50%)
    6 / 522 (1.15%)
         occurrences all number
    10
    6
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    7 / 257 (2.72%)
    16 / 522 (3.07%)
         occurrences all number
    8
    18
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    8 / 257 (3.11%)
    18 / 522 (3.45%)
         occurrences all number
    8
    19
    Muscle spasms
         subjects affected / exposed
    3 / 257 (1.17%)
    11 / 522 (2.11%)
         occurrences all number
    3
    12
    Myalgia
         subjects affected / exposed
    8 / 257 (3.11%)
    15 / 522 (2.87%)
         occurrences all number
    8
    15
    Osteoarthritis
         subjects affected / exposed
    3 / 257 (1.17%)
    11 / 522 (2.11%)
         occurrences all number
    4
    11
    Pain in extremity
         subjects affected / exposed
    1 / 257 (0.39%)
    11 / 522 (2.11%)
         occurrences all number
    1
    11
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    6 / 257 (2.33%)
    7 / 522 (1.34%)
         occurrences all number
    7
    7
    Lower respiratory tract infection
         subjects affected / exposed
    7 / 257 (2.72%)
    7 / 522 (1.34%)
         occurrences all number
    7
    9
    Nasopharyngitis
         subjects affected / exposed
    13 / 257 (5.06%)
    27 / 522 (5.17%)
         occurrences all number
    15
    31
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 257 (3.50%)
    19 / 522 (3.64%)
         occurrences all number
    10
    20
    Urinary tract infection
         subjects affected / exposed
    5 / 257 (1.95%)
    24 / 522 (4.60%)
         occurrences all number
    5
    28
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    6 / 257 (2.33%)
    10 / 522 (1.92%)
         occurrences all number
    6
    11
    Gout
         subjects affected / exposed
    2 / 257 (0.78%)
    11 / 522 (2.11%)
         occurrences all number
    2
    11
    Hyperuricaemia
         subjects affected / exposed
    5 / 257 (1.95%)
    22 / 522 (4.21%)
         occurrences all number
    5
    22
    Type 2 diabetes mellitus
         subjects affected / exposed
    7 / 257 (2.72%)
    10 / 522 (1.92%)
         occurrences all number
    7
    10

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jan 2017
    Major changes to the protocol included revision of the definition of true abstinence in the Inclusion Criteria.
    22 Mar 2017
    Major changes to the protocol included: (a) updated text pertaining to the bempedoic acid mechanism of action based on new information; (b) reduced planned enrollment; (c) removed the requirement that strata (statin dose and participant status) could not be capped in order to ensure adequate number of participant characteristics if imbalance occurred; (d) revised secondary and tertiary endpoints as well as added safety endpoints; (e) added additional clinical and telephone visits for participants taking simvastatin 40 milligrams (mg); (f) added implantable, injectable, or topical method as allowable forms of hormonal contraception; (g) added requirement that women use 2 rather than 1 form of acceptable contraception; (h) added additional fasting LDL-C assessment after the Run-in period to Inclusion Criteria. Removed the allowance of repeating a screening LDL-C measurement after Visit S1; (i) clarified the timing of the collection of lipid values; (j) further defined Inclusion Criteria around PAD and cerebrovascular atherosclerotic disease; (j) added eGFR <45 mL/min/1.73 m^2 in participants taking simvastatin as exclusionary; (k) excluded participants who have enrolled in a study of an experimental siRNA inhibitor of PCSK9; (l) clarified time period during which participants should not intend to become pregnant; (m) altered the 3-month time period for not using the certain drugs prior to screening; (n) removed collection of optional genetic sampling, reserve samples, and PK sample collection on Day 1; (o) added windows to all visits; (p) removed manufacturing contact details; (q) modified the monitoring and management of CK values for asymptomatic participants; (r) revised statistical sections; (s) added details to clarify the time period and reporting process for the collection of adverse events; (t) added sections related to adverse events; (u) made administrative changes where required to correct inconsistencies, add clarification, or correct errors.
    09 May 2017
    Major changes to the protocol included: (a) Simvastatin at average daily doses of 40 mg or greater was added as a prohibited medication. The protocol was amended to remove study visits at Weeks 16, 20, 28, and 32 that were only for participants taking simvastatin 40 mg/day. A letter was provided to all investigators with instructions on how to proceed for enrolled participants receiving simvastatin 40 mg/day. (b) Increased number of participants to be enrolled from approximately 525 to approximately 750 participants (500 bempedoic acid; 250 placebo), as was included in the original protocol and Amendment 1. The reason for the increase in participants was due to the decision to discontinue investigational medicinal product in participants receiving simvastatin at average daily doses ≥40 mg across the bempedoic acid program, therefore resulting in an overall smaller safety database than planned. Based on this decision, the sample size in this study was increased back to the original sample size of 750 participants to ensure the safety database was sufficiently large for an approval of a low-density lipoprotein cholesterol (LDL-C) lowering indication. (c) Clarified that the requirement to have ≥80% treatment compliance during the Run-in Period refers to the average treatment compliance over the entire Run-in Period (compliance measured at Visits S3 and T1). (d) Corrected the visit window for Week 24 within the protocol text and Appendix 1, Schedule of Events, to reflect 168 ± 7 days. (d) Updated the definition of serious adverse events to include hospitalizations for preplanned surgeries and/or elective surgeries.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu May 02 21:30:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA