Healthy Subjects
Conditions
Keywords
Healthy Subjects, Bioequivalence
Brief summary
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 low density lipoprotein cholesterol (LDL-C) lowering and atherosclerotic cardiovascular disease risk reduction in patients unable to reach individualized serum LDL-C levels. This study will test the bioequivalence of a test fixed dose combination (FDC) product versus the co-administered individual reference products.
Detailed 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.
Interventions
DRUGBempedoic acid
180 mg film coated tablet administered as FDC or co-administered with ezetimibe Component of FDC
DRUGEzetimibe
10 mg tablet administered as FDC or co-administered with bempedoic acid Component of FDC
DRUGRosuvastatin
20 mg film coated tablet administered individually or as FDC Component of FDC
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion 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, and if with a non-vasectomized nor infertile male partner, agree to use an appropriate method of contraception. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter Area Under the Curve (AUC) | 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 | 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. |
| Pharmacokinetic Parameter Maximum Observed Concentration (Cmax) | 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 will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter Time to Reach Maximum Observed Concentration (Tmax) | 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 | Time to reach maximum observed concentration (Tmax) will be assessed. |
| Pharmacokinetic Parameter Terminal Half-life (t1/2) | 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 | Terminal half-life (t1/2) will be assessed using noncompartmental methods, where applicable. |
| Pharmacokinetic Parameters (AUCinf) | 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 | AUC from time of dosing (t=0h) extrapolated to infinity (AUCinf) will be assessed using noncompartmental methods, where applicable. |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Baseline to end of study, up to approximately 2 months | AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). |
| Pharmacokinetic Parameter First Order Rate Constant Associated With The Terminal Portion of the Concentration-Time Curve (Kel) | 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 | First order rate constant associated with the terminal portion of the concentration-time curve (Kel) was assessed using noncompartmental methods, where applicable. |
| Pharmacokinetic Parameters (AUClast/AUCinf) | 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 | AUClast/AUCinf will be assessed using noncompartmental methods, where applicable. |
Countries
Portugal
Outcome results
None listed