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HypercholesterolemiaPhase 3CLEAR WisdomNCT02991118

Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk

A Phase 3 study testing bempedoic acid in people with Hypercholesterolemia and Atherosclerotic Cardiovascular Disease, run by Esperion Therapeutics, Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to see if bemedoic acid (ETC-1002) is effective versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol not adequately controlled by their current therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bempedoic acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
779 participants
Where
2 sitesUnited States
Study dates
18 Nov 2016to 22 Aug 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Fasting LDL-C ≥100 mg/dL
  • High cardiovascular risk (diagnosis of HeFH and/or ASCVD)
  • Be on maximally tolerated lipid-modifying therapy (LMT), including maximally tolerated statin either alone or in combination with other LMTs

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Study site

    Clearwater, Florida

  • Study site

    Georgetown, Texas

Other trials in United States

About this study

Official title: 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

The purpose of this study is to see if bemedoic acid (ETC-1002) is effective versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol not adequately controlled by their current therapy.

Being tested
bempedoic acid, placebo
Keywords
hyperlipidemia, cholesterol, familial hypercholesterolemia, atherosclerotic cardiovascular disease, ASCVD, HeFH, LDL
Medical subject headings
Hypercholesterolemia, Atherosclerosis, Hyperlipidemias, Hyperlipoproteinemia Type II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bempedoic acidDrug

    Also called ETC-1002

    bempedoic acid 180 mg tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)

  • placeboDrug

    Also called placebo control

    Matching placebo tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)

Study groups in NCT02991118
Study groupRoleWhat they receive
bempedoic acidExperimentalbempedoic acid 180 mg/day
Receives: Drug: bempedoic acid
PlaceboPlacebo comparatorPlacebo control
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)

    Baseline is 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. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (atherosclerotic cardiovascular diseases [ASCVD] and heterozygous familial hypercholesterolemia [HeFH]) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 are imputed using multiple imputation method taking into account adherence to treatment.

    Measured: Baseline; Week 12

Secondary outcomes (7)
  1. Percent Change From Baseline to Week 24 in LDL-C

    Baseline is 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. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 24 were imputed using multiple imputation method taking into account adherence to treatment.

    Measured: Baseline; Week 24

  2. Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

    Baseline is 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. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing non-HDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.

    Measured: Baseline; Week 12

  3. Percent Change From Baseline to Week 12 in Total Cholesterol (TC)

    Baseline is 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. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing TC data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.

    Measured: Baseline; Week 12

  4. Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B)

    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. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing apo B data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.

    Measured: Baseline; Week 12

  5. Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)

    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.

    Measured: Baseline; Week 12

  6. Change From Baseline to Week 12 in LDL-C

    Baseline is 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. Analysis was conducted using descriptive statistics by treatment group using observed data.

    Measured: Baseline; Week 12

  7. Change From Baseline to Week 24 in LDL-C

    Baseline is 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. Analysis was conducted using descriptive statistics by treatment group using observed data.

    Measured: Baseline; Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2016 (estimated)
  2. Study start18 Nov 2016
  3. Primary completion22 Aug 2018
  4. Study completion22 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
779 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02991118
Sponsor's protocol ID
1002-047
Other IDs
2016-003486-26, 2016
Acronym
CLEAR Wisdom
Status last verified
Apr 2020
First submitted
9 Dec 2016
Last updated
27 Apr 2020
Data monitoring committee
Yes

Publications

  • Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, Lalwani ND, Patel PM, Zhao X, Duell PB. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019 Nov 12;322(18):1780-1788. doi: 10.1001/jama.2019.16585.

    PubMed 31714986
  • Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.

    PubMed 27892461
  • Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.

    PubMed 21067804
  • Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3.

    PubMed 26039521
  • Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013 Mar;19(2):139-49. doi: 10.18553/jmcp.2013.19.2.139.

    PubMed 23461430
  • Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. No abstract available.

    PubMed 24222016
  • Ballantyne CM, Bays HE, Louie MJ, Smart J, Zhang Y, Ray KK. Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid. J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.

    PubMed 35916348
  • Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Flaim J, Ye Z, Catapano AL. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol. 2020 Oct 1;5(10):1124-1135. doi: 10.1001/jamacardio.2020.2314.

    PubMed 32609313

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing bempedoic acid in people with Hypercholesterolemia and Atherosclerotic Cardiovascular Disease, run by Esperion Therapeutics, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) (time frame: Baseline; Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02991118, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2020.

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