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

NCT07474649 | Not Yet Recruiting Phase 3

• 2 other identifiers: DSE-BMP-0005-CIS-MA2025-524625-41
• Study Type: interventional
• Target: 103
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Coronary Atherosclerosis; Mixed Dyslipidemia; Hypercholesterolemia

Keywords

Coronary atherosclerosis; Primary non-familial hypercholesterolaemia; Mixed dyslipidaemia; Bempedoic acid; Ezetimibe; Atorvastatin; Rosuvastatin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Key Secondary: Annualised change in normalised non-calcified plaque volume (PV)

  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)

  Baseline up to 12 months

• Change in the absolute Agatston coronary artery calcium (CAC) score

  Baseline up to 12 months

• Annualised ΔTotal Plaque Volume (TPV)

  Baseline up to 12 months

• Percentage of participants with regression in TPV (i.e., negative ΔTPV)

  Baseline up to 12 months

Study Arms (1)

Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

EXPERIMENTAL

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; Drug: Ezetimibe; Drug: Rosuvastatin; Drug: Atorvastatin

Interventions

Bempedoic acid DRUG

FDC: 180 mg

Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

Ezetimibe DRUG

FDC: 10 mg

Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

Rosuvastatin DRUG

20 mg dose

Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

Atorvastatin DRUG

40 mg dose

Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this trial, a potential participant must meet all of the following criteria:
• Age ≥18 years
• Having provided informed consent for participation in this trial
• Lipid-lowering treatment-naïve
• 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')
• Able to provide informed consent

You may not qualify if:

• A potential participant who meets any of the following criteria will be excluded from participation in this trial:
• Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
• 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.
• Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
• History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\])
• 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
• 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 \[ULN\])
• Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
• Known estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73m² and/or receiving dialysis
• Active malignancy (not including non-melanoma skin cancer)
• Pregnant or breastfeeding
• Body mass index (BMI) \>35 kg/m²
• Anticipated life expectancy \<52 weeks at the discretion of the local investigator
• 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
• Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)

Sponsors & Collaborators

• Daiichi Sankyo: lead

MeSH Terms

Conditions

Coronary Artery Disease; Hypercholesterolemia

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Ezetimibe; Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Central Study Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): October 2, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.