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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-519850-35-00 | EU Trial (CTIS) Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test Formulation | Experimental | 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). |
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| Reference Formulation | Active Comparator | Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + rosuvastatin 20 mg (reference formulation). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bempedoic acid | Drug | 180 mg film coated tablet administered individually or as FDC Component of FDC |
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| 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) post-dose |
| Pharmacokinetic Parameter 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) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameters (AUCinf and AUClast/AUCinf) | AUC from time of dosing (t=0h) extrapolated to infinity (AUCinf) and 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) post-dose |
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A participant is eligible for the study if he/she fulfills all of the following inclusion criteria:
A participant is not eligible for the study at Screening if he/she fulfills any of the exclusion criteria as specified in the protocol.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Porto | 4250-449 | Portugal |
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| ID | Term |
|---|---|
| C581236 | 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid |
| D000069438 | Ezetimibe |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Ezetimibe | Drug | 10 mg tablet administered individually or as FDC Component of FDC |
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| Rosuvastatin | Drug | 20 mg film coated tablet administered individually or as FDC Component of FDC |
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| 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) post-dose |
| 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) post-dose |
| 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) post-dose |
| 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, up to approximately 2 months |
| D013449 |
| Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |