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

Daiichi Sankyo58 enrolled

Overview

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) product versus the co-administered individual reference products.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Subjects

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Pharmacokinetic Parameter Area Under the Curve (AUC)

Area under the curve (AUC) from time of dosing (t=0hours) to time 72 hours (AUC72hours) or AUC from time of dosing (t=0hours) to the time of last measurable (non-zero) concentration (AUClast) will be assessed using noncompartmental methods.

Time frame: Pre-dose (t=0hours), 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.

Secondary Outcomes

Pharmacokinetic Parameters (AUCinf)

AUC from time of dosing (t=0hours) extrapolated to infinity (AUCinf) will be assessed using noncompartmental methods, where applicable.

Pharmacokinetic Parameters (AUClast/AUCinf)

AUClast/AUCinf will be assessed using noncompartmental methods, where applicable.

Pharmacokinetic Parameter Time to Reach Maximum Observed Concentration (Tmax)

Time to reach maximum observed concentration (Tmax) will be assessed.

Pharmacokinetic Parameter Terminal Half-life (t1/2)

Terminal half-life (t1/2) will be assessed using noncompartmental methods, where appropriate.

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) will be assessed using noncompartmental methods, where appropriate.

Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)

AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).

Time frame: Baseline to end of study, approximately 57 days