A Study Evaluating Bioequivalence of a Fixed Dose Combination Versus Individual Tablets of Bempedoic Acid, Ezetimibe, and Atorvastatin

A Randomized, Single-Center, Open-Label, Single-Dose, 4-Period, 2-Sequence, Fully Replicate Crossover Study To Assess The Bioequivalence Of A Test Fixed Dose Combination Product Versus The Co-Administered Individual Reference Products Containing Bempedoic Acid 180 MG, Ezetimibe 10 mg And Atorvastatin 40 mg In Healthy Participants

Monotherapies for lowering LDL-C often do not achieve target lipid levels because they act on a single pathway, which may be insufficient in patients with high cardiovascular risk or complex lipid profiles. Triple combination therapies, targeting multiple mechanisms of cholesterol metabolism simultaneously, have demonstrated superior LDL-C reduction and better achievement of guideline recommended LDL-C goals. Additionally, combining treatments into a single regimen can improve patient adherence and compliance, further enhancing clinical outcomes. This study will test the bioequivalence of a test fixed dose combination (FDC) vs the coadministration of individual tablets.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Bempedoic acid; Drug: Ezetimibe; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Porto, Portugal, 4250-449
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

A participant is eligible for the study if he/she fulfills all of the following inclusion criteria:

1. Healthy male and female participants ≥18 and ≤60 years, at the time of signing the informed consent.
2. Body mass index (BMI) ≥18.5 and ≤30.0 kg/m^2.
3. Female participants of childbearing potential agree to undergo pregnancy tests, and if with a non-vasectomized nor infertile male partner, agree to use an appropriate method of contraception (i.e., abstinence, hormonal, intrauterine device, bilateral tubal occlusion).
4. No clinically relevant diseases captured in medical history.
5. No clinically relevant abnormalities on physical examination.
6. No clinically relevant abnormalities on vital signs.
7. No clinically relevant abnormalities on 12-lead electrocardiogram (ECG).
8. No clinically relevant abnormalities on clinical laboratory tests.
9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) above the upper limit of normal range (ULN).
10. Estimated renal creatinine clearance (CrCl) above the lower limit of normal range, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m^2.
11. Willingness to accept and comply with all study procedures and restrictions.
12. Non-smoker or ex-smoker (i.e., someone who abstained from using tobacco- or nicotine-containing products for at least 3 months prior to Screening).
13. Ability to comprehend and willingness to freely sign the informed consent.

A participant is not eligible for the study at Screening if he/she fulfills any of the exclusion criteria as specified in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Formulation; Healthy participants who are randomized to receive the fixed dose triplet combination with bempedoic acid 180 mg/ezetimibe 10 mg/atorvastatin 40 mg (test formulation).	Drug: Bempedoic acid; 180 mg film coated tablet administered individually or as FDC (Component of FDC); Other Names: Nilemdo®; Drug: Ezetimibe; 10 mg tablet administered individually or as FDC (Component of FDC); Other Names: Ezetrol®; Drug: Atorvastatin; 40 mg tablet administered individually or as FDC (Component of FDC); Other Names: Sortis®
Active Comparator: Reference Formulation; Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + atorvastatin 40 mg (reference formulation).	Drug: Bempedoic acid; 180 mg film coated tablet administered individually or as FDC (Component of FDC); Other Names: Nilemdo®; Drug: Ezetimibe; 10 mg tablet administered individually or as FDC (Component of FDC); Other Names: Ezetrol®; Drug: Atorvastatin; 40 mg tablet administered individually or as FDC (Component of FDC); Other Names: Sortis®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Area Under the Curve (AUC)	Area under the curve (AUC) from time of dosing (t=0h) to time 72 hours (AUC72h) or AUC from time of dosing (t=0h) to the time of last measurable (non-zero) concentration (AUClast) will be assessed using noncompartmental methods.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Maximum Observed Concentration (Cmax)	Maximum observed concentration will be assessed.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Time to Reach Maximum Observed Concentration (Tmax)	Time to reach maximum observed concentration (Tmax) will be assessed.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Pharmacokinetic Parameters (AUCinf)	AUC from time of dosing (t=0h) extrapolated to infinity (AUCinf) will be assessed using noncompartmental methods.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Pharmacokinetic Parameters (AUClast/AUCinf)	AUClast/AUCinf will be assessed using noncompartmental methods.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Pharmacokinetic Parameter Terminal Half-life (t1/2)	Terminal half-life (t1/2) will be assessed using noncompartmental methods.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Pharmacokinetic Parameter First Order Rate Constant Associated With The Terminal Portion of the Concentration-Time Curve (Kel)	First order rate constant associated with the terminal portion of the concentration-time curve (Kel) was assessed using noncompartmental methods.	Pre-dose (t=0h), and at 0.17 hours (10 minutes), 0.5 hours, 0.75 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours (Day 2), 48 hours (Day 3), and 72 hours (Day 4) postdose
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)	AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).	Baseline to end of study, approximately 82 days

Collaborators and Investigators

• Sponsor: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2025
• Primary Completion (Actual): January 28, 2026
• Study Completion (Actual): January 28, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Pyrroles; Heptanoic Acids; Azetidines; Azetines; Atorvastatin; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: DSE-BMP-0001-CIS-MA; 2024-519849-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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