A Study of Bempedoic Acid/Ezetimibe/High-intensity Statin in Patients Without Cardiovascular Events

Effects of Bempedoic Acid/Ezetimibe/High-intensity Statin on Plaque Regression and Stabilisation of Coronary Atherosclerosis Among Patients Without Cardiovascular Events

The overall objective of the trial is to evaluate the effect of the triple therapy consisting of bempedoic acid (BA), ezetimibe (EZE), and high-intensity atorvastatin or rosuvastatin on changes in coronary plaque burden and plaque morphology in patients with coronary atherosclerosis without significant obstructive coronary artery disease and without prior history of an ischemic vascular event.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypercholesterolemia; Mixed Dyslipidemia; Coronary Atherosclerosis
• Intervention / Treatment: Drug: Bempedoic acid; Drug: Ezetimibe; Drug: Rosuvastatin; Drug: Atorvastatin

Detailed Description

The primary objective is to evaluate the effectiveness of the triple therapy in reducing plaque burden.

The key secondary objective is to assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.

• Study Type: Interventional
• Enrollment (Estimated): 103
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo_us@daiichisankyo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to be eligible to participate in this trial, a potential participant must meet all of the following criteria:

1. Age ≥18 years
2. Having provided informed consent for participation in this trial
3. Lipid-lowering treatment-naïve

4. Presence of extensive coronary atherosclerosis meeting all of the criteria below:

   • Unequivocal atherosclerosis in ≥5 American Heart Association (AHA) coronary segments (corresponding to a risk equivalent of obstructive coronary artery disease) and coronary artery disease - reporting and data system (CAD-RADS) category 1, 2, or 3
   • Not expected to be a candidate for revascularisation during the duration of the trial
   • Untreated LDL-C ≥2.6 mmol/L and ≤4.5 mmol/L (where a diet without pharmacological treatment is considered 'untreated')
5. Able to provide informed consent

Exclusion Criteria:

A potential participant who meets any of the following criteria will be excluded from participation in this trial:

1. Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
2. Known contraindication for BA, EZE, atorvastatin, and/or rosuvastatin. A participant with a contraindication for atorvastatin, can be assigned to triple therapy with rosuvastatin, and vice versa.
3. Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
4. History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG])
5. Significant stenosis in the left main artery (≥50%) or proximal LAD artery (≥70%), or 3-vessel coronary artery disease (≥70% stenosis in major branches), clinically indicated for revascularisation
6. Known significant liver disease (e.g., positive hepatitis B or hepatitis C serology) or significant hepatic dysfunction (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >3 x upper limit of normal [ULN])
7. Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
8. Known estimated glomerular filtration rate (eGFR) <40 mL/min/1.73m² and/or receiving dialysis
9. Active malignancy (not including non-melanoma skin cancer)
10. Pregnant or breastfeeding
11. Body mass index (BMI) >35 kg/m²
12. Anticipated life expectancy <52 weeks at the discretion of the local investigator
13. Requiring emergent procedures or having any evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, severe congestive heart failure (New York Heart Association [NYHA] III or IV), or acute pulmonary oedema
14. Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
15. Complex congenital heart disease
16. Known or suspected severe valvular heart disease or valvular heart disease anticipated to require intervention within 52 weeks at the discretion of the local investigator
17. Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
18. Intracoronary stents
19. Prior pacemaker, internal defibrillator, or abandoned lead implantation
20. Prosthetic heart valves
21. Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
22. Use of any experimental or investigational drug within 40 days or 5 half-lives prior to Screening (whichever is longer), or parallel participation in another interventional study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin; Treatment-naïve participants with coronary atherosclerosis and primary non-familial hypercholesterolaemia or mixed dyslipidaemia who will receive daily treatment with BA/EZE FDC, together with either 20 mg rosuvastatin or 40 mg atorvastatin.	Drug: Bempedoic acid; FDC: 180 mg; Drug: Ezetimibe; FDC: 10 mg; Drug: Rosuvastatin; 20 mg dose; Drug: Atorvastatin; 40 mg dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualised change in percentage plaque burden (Δ%PB)	This endpoint will evaluate the effectiveness of the triple therapy in reducing plaque burden (PB).	Baseline up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary: Annualised change in normalised non-calcified plaque volume (PV)	This endpoint will assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.	Baseline up to 12 months
Percentage of participants with regression in normalised total plaque volume (TPV), normalised non-calcified PV, and normalised low attenuation PV at EoT (i.e., ΔPV and Δnon-calcified PV, and Δlow-attenuation PV)	This endpoint will evaluate the potential impact of the triple therapy on total plaque volume (TPV) regression, non-calcified PV regression, and low attenuation PV regression.	Baseline up to 12 months
Annualised ΔTotal Plaque Volume (TPV)	This endpoint will evaluate the effectiveness of the triple therapy in reducing TPV.	Baseline up to 12 months
Percentage of participants with regression in TPV (i.e., negative ΔTPV)	This endpoint will assess the proportion of participants exhibiting regression in TPV with triple therapy.	Baseline up to 12 months
Absolute annualised change in fractional flow reserve derived from computed tomography (FFRCT) of the vessel with the lowest FFR at Baseline	This endpoint will assess changes in non-invasive coronary flow reserve.	Baseline up to 12 months
Absolute annualised change in FFRCT of the average of 3 main epicardial coronary arteries (left anterior descending artery [LAD], circumflex artery [Cx], right coronary artery [RCA])	This endpoint will assess changes in non-invasive coronary flow reserve.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker total cholesterol	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker low-density lipoprotein cholesterol (LDL-C)	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker high-density lipoprotein cholesterol (HDL-C)	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker non-high-density lipoprotein cholesterol (non-HDL-C)	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarkers lipoprotein a (Lp(a)) and apolipoprotein B (apoB)	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker high-sensitive C reactive protein (hs-CRP)	This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.	Baseline up to 12 months
Annualised changes in Framingham steatosis index (FSI) and fibrosis-4 (Fib-4)	This endpoint will assess the potential impact of the triple therapy on measures of liver health.	Baseline up to 12 months
Cumulative incidence of adverse events (AEs) under triple therapy during the trial	This endpoint will monitor and assess adverse events (AEs) under triple treatment.	Baseline up to 12 months
Rate of treatment discontinuation during the trial	This endpoint will to determine the rate and reasons for treatment discontinuation among trial participants receiving triple therapy.	Baseline up to 12 months
Change in the absolute Agatston coronary artery calcium (CAC) score	This endpoint will evaluate the potential impact of the triple therapy on coronary calcification. CAC measures the total area and density of calcified plaque in the heart's arteries, ranging from 0 to over 400. A score of 0 indicates no plaque, while higher scores indicate increased risk of cardiovascular events, with >400 indicating extensive disease.	Baseline up to 12 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): October 2, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Atorvastatin; Rosuvastatin; Ezetimibe; Coronary atherosclerosis; Bempedoic acid; Primary non-familial hypercholesterolaemia; Mixed dyslipidaemia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Nutritional and Metabolic Diseases; Hypercholesterolemia; Coronary Artery Disease; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Pyrroles; Heptanoic Acids; Sulfonamides; Sulfones; Azetidines; Azetines; Fluorobenzenes; Hydrocarbons, Fluorinated; Atorvastatin; Rosuvastatin Calcium; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: DSE-BMP-0005-CIS-MA; 2025-524625-41 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No