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

Daiichi Sankyo

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: Mixed Dyslipidemia; Coronary Atherosclerosis; Hypercholesterolemia

Treatments: Drug: Bempedoic acid; Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Ezetimibe

Study type: Interventional

Funder types: Industry

Identifiers

NCT07474649

2025-524625-41 (Other Identifier)

DSE-BMP-0005-CIS-MA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 103 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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103 participants in 1 patient group

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

Experimental group

Description:

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.

Treatment:

Drug: Ezetimibe

Drug: Atorvastatin

Drug: Rosuvastatin

Drug: Bempedoic acid