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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameter Area Under the Curve (AUC)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A participant is eligible for the study if he/she fulfills all of the following inclusion criteria:
- •Healthy male and female participants ≥18 and ≤60 years, at the time of signing the informed consent.
- •Body mass index (BMI) ≥18.5 and ≤30.0 kg/m^
- •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).
- •No clinically relevant diseases captured in medical history.
- •No clinically relevant abnormalities on physical examination.
- •No clinically relevant abnormalities on vital signs.
- •No clinically relevant abnormalities on 12-lead electrocardiogram (ECG).
- •No clinically relevant abnormalities on clinical laboratory tests.
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) above the upper limit of normal range (ULN).
- •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^
- •Willingness to accept and comply with all study procedures and restrictions.
- •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).
- •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
排除标准
- •as specified in the protocol.
研究组 & 干预措施
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).
干预措施: Bempedoic acid (Drug)
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).
干预措施: Ezetimibe (Drug)
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).
干预措施: Atorvastatin (Drug)
Reference Formulation
Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + atorvastatin 40 mg (reference formulation).
干预措施: Bempedoic acid (Drug)
Reference Formulation
Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + atorvastatin 40 mg (reference formulation).
干预措施: Ezetimibe (Drug)
Reference Formulation
Healthy participants who are randomized to receive co-administration of bempedoic acid 180 mg + ezetimibe 10 mg + atorvastatin 40 mg (reference formulation).
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Pharmacokinetic Parameter Area Under the Curve (AUC)
时间窗: 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.
Maximum Observed Concentration (Cmax)
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)(Baseline to end of study, approximately 82 days)