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

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT07182383

2024-519850-35-00 (EU Trial (CTIS) Number)

DSE-BMP-0002-CIS-MA

Details and patient eligibility

About

The recommended first-line treatment of cardiovascular disease is a statin monotherapy; however, combination therapies represent an opportunity for an individualized, patient centered approach to lower low density lipoprotein cholesterol (LDL-C) and reduce atherosclerotic cardiovascular disease risk in patients unable to reach individualized serum LDL-C levels. This study will test the bioequivalence of a test fixed dose combination (FDC) vs the co-administration of individual tablets.

Full description

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.

Enrollment: 58 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 resulting in negative results, non-lactating status, and agree to use accepted contraceptive method from at least 4 weeks prior to admission to the first study period until the end of the study, 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) ≤1.5 times 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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58 participants in 2 patient groups

Test Formulation

Experimental group

Description:

Healthy participants who are randomized to receive the fixed dose triplet combination with bempedoic acid 180 mg/ezetimibe 10 mg/rosuvastatin 20 mg (test formulation).

Treatment:

Drug: Ezetimibe

Drug: Bempedoic acid

Drug: Rosuvastatin

Reference Formulation

Active Comparator group

Description:

Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + rosuvastatin 20 mg (reference formulation).

Treatment:

Drug: Ezetimibe

Drug: Bempedoic acid

Drug: Rosuvastatin