An Open-Label Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bempedoic Acid in Pediatric Patients (6 to 17 Years of Age) With Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 39
- 主要终点
- Plasma trough concentration of ETC-1002
研究概览
简要总结
Multiple-dose study to measure pharmacokinetics, pharmacodynamics and safety of bempedoic acid in pediatric participants 6 to 17 years of age with HeFH.
详细描述
Dose-selection based on body weight will be determined for use in pediatric clinical development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant's parent(s)/guardian(s) must be willing to provide written informed consent and the participant must provide informed assent before any study-specific procedures are performed;
- •Participant must be aged 6-17 years old and willing to swallow tablets;
- •Participant must weigh at least 16 kilograms (kg);
- •Participant must have a diagnosis of HeFH prior to receiving the first dose of study medication at Treatment Visit T1 per Make Early Diagnosis to Prevent Early Deaths project (MEDPED) criteria by meeting at least one of the following clinical criteria:
- •Documented diagnosis of HeFH determined by positive genetic testing; or
- •Documented LDL-C or TC meeting one or more of the following criteria:
- •i. LDL-C >200 milligrams per deciliter (mg/dL) (5.2 millimole per liter [mmol/L]) or TC >270 mg/dL (7.0 mmol/L), with no first- second- or third-degree relative with documented FH diagnosis (general population); or ii. LDL-C >155 mg/dL (4.0 mmol/L) or TC >220 mg/dL (5.7 mmol/L), and also having a first-degree relative with documented familial hypercholesterolemia (FH) diagnosis; or iii. LDL-C >165 mg/dL (4.3 mmol/L) or TC >230 mg/dL (5.9 mmol/L), and also having a second-degree relative with documented FH diagnosis; or iv. LDL-C >170 mg/dL (4.4 mmol/L) or TC >240 mg/dL (6.2 mmol/L), and also having a third-degree relative with documented FH diagnosis
- •Current treatment with approved stable lipid-modifying therapy (LMT), including an optimal dose of statin with or without other LMT(s), at stable dose for at least 4 weeks prior to Treatment Visit T1 (6 weeks for fibrates; however, gemfibrozil is not allowed in participants taking a statin as per coadministration instructions defined in the statin label). Participants must remain on that stable dose throughout the duration of the trial. Optimal dose of statin will be determined by the investigator using their medical judgment and available sources, including the participant's self-reported history of LMT. A participant's optimal dose of statin is defined as meeting one of the following criteria:
- •the highest approved dose of statin prescribed for the age of the participant based on regional practice or local guidelines; or
- •less than the highest approved dose of statin, including no statin, prescribed for the age of the participant based on regional practice or local guidelines (including no statin) if: i. the participant has previously taken 2 or more statin therapies at any dose and not able to tolerate or unresponsive due to their mutations (null); or ii. the participant has previously taken 1 or more statin therapies at any dose and is unwilling to attempt another statin at any dose or advised by a physician to not attempt another statin at any dose.
- •Participant/parent and investigator attestation to the participant's unwillingness to attempt and/or physician advice to not attempt additional statin therapy will be recorded.
排除标准
- •Participant has a diagnosis of homozygous familial hypercholesterolemia (HoFH) or compound HeFH;
- •Participant has a fasting triglyceride (TG) level ≥400 mg/dL (4.5 mmol/L);
- •Participant has uncontrolled hypothyroidism, including a value for thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or >1.5 × the upper limit of normal (ULN);
- •Participant has liver disease or dysfunction, including:
- •positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibodies (HCV-AB), or
- •serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥2 × ULN and/or serum total bilirubin (TB) value ≥2 × ULN. If the serum TB value is ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and, if consistent with Gilbert's disease or if the participant has a history of Gilbert's disease, the participant may be enrolled in the study.
- •Participant has renal dysfunction or glomerulonephritis, including an estimated glomerular filtration rate (eGFR) <75 milliliters/minute/1.73 square meter (mL/min/1.73 m^2).
- •Other protocol defined inclusion and exclusion criteria.
研究组 & 干预措施
Cohort 1
Participants at 16 to <30 kilograms (kg) body weight at screening receiving once daily 60 milligrams (mg) bempedoic acid for 8 weeks followed by 90 mg bempedoic acid for 8 weeks.
干预措施: Bempedoic acid (Drug)
Cohort 2
Participants at 30 to 60 kg body weight at screening receiving once daily120 mg bempedoic acid for 8 weeks followed by 150 mg bempedoic acid for 8 weeks.
干预措施: Bempedoic acid (Drug)
Cohort 3
Participants at greater than 60 kg body weight at screening receiving once daily 180 mg bempedoic acid for 8 weeks.
干预措施: Bempedoic acid (Drug)
结局指标
主要结局
Plasma trough concentration of ETC-1002
时间窗: 8 weeks of steady-state dosing
Area under the plasma concentration-time curve (AUC,ss) of ETC-1002
时间窗: 8 weeks of steady-state dosing
Average plasma concentration (Cavg,ss) of ETC-1002
时间窗: 8 weeks of steady-state dosing
Maximum plasma concentration (Cmax,ss) of ETC-1002
时间窗: 8 weeks of steady-state dosing
Observed Trough Plasma Concentration of ETC-1002 Following 8 Weeks of Steady State Dosing of Bempedoic Acid
时间窗: Week 8 pre-dose
Blood plasma samples were collected and analyzed to determine the plasma trough concentration of ETC-1002 following 8 weeks of steady-state dosing of bempedoic acid. The data presented here is for participants who received tablet formulation only.
Model-based Steady State Area Under the Concentration-time Curve Over 24 Hours (AUC,24ss) of ETC-1002
时间窗: 24 hours
Blood plasma samples were collected and analyzed to determine the AUC,24ss of ETC-1002 over 24 hours. The data presented here is for participants who received tablet formulation only.
Model-based Steady State Average Plasma Concentration (Cavg,ss) of ETC-1002
时间窗: Week 8, 24 hours post-dose at steady state
Blood plasma samples were collected and analyzed to determine the Cavg,ss of ETC-1002. Cavg was calculated by empirical Bayesian estimated pediatric exposure over 24 hours divided by 24 (AUC24hr.ss / 24). The data presented here is for participants who received tablet formulation only.
Model-based Steady State Maximum Plasma Concentration (Cmax,ss) of ETC-1002
时间窗: Day 1: 1-hour and 4 hours post-dose; Week 4 pre-dose; Week 8 pre-dose
Blood plasma samples were collected and analyzed to determine the Cmax,ss of ETC-1002. The data presented here is for participants who received tablet formulation only.
次要结局
- Absolute change from Baseline in hsCRP(Baseline and at Weeks 8 and 16)
- Plasma trough concentration of ESP15228(8 weeks of steady-state dosing)
- Plasma concentration at 4 hours (C4hr) of ETC-1002(Day 1)
- C4hr of ESP15228(Day 1)
- Exposure/LDL-C response relationship(8 weeks of steady-state dosing)
- Percent change from Baseline in low-density lipoprotein cholesterol (LDL-C)(Baseline and at Weeks 8 and 16)
- Absolute change from Baseline in LDL-C(Baseline and at Weeks 8 and 16)
- Percent change from Baseline in non-high-density lipoprotein cholesterol (non-HDL-C)(Baseline and at Weeks 8 and 16)
- Absolute change from Baseline in non-HDL-C(Baseline and at Weeks 8 and 16)
- Percent change from Baseline in total cholesterol (TC)(Baseline and at Weeks 8 and 16)
- Absolute change from Baseline in TC(Baseline and at Weeks 8 and 16)
- Percent change from Baseline in high-sensitivity C-reactive protein (hsCRP)(Baseline and at Weeks 8 and 16)
- Acceptability of taste using a dosing acceptability questionnaire(Up to Week 16)
- Acceptability of ease of swallowing using a dosing acceptability questionnaire(Up to Week 16)
- Number of participants reporting Serious adverse events (SAEs) and non-SAEs(Up to Week 16)
- Observed Trough Plasma Concentration of ESP15228(Week 8 pre-dose)
- Observed Plasma Concentration at 4 Hours (C4hr) of ETC-1002(Day 1: 4 hours post-dose)
- Observed C4hr of ESP15228(Day 1: 4 hours post-dose)
- Simulated Percent Change From Baseline in Exposure/ Low-Density Lipoprotein-Cholesterol (LDL-C)(Baseline and Week 12)
- Observed Percent Change From Baseline in LDL-C(Baseline and 8 Weeks post-treatment)
- Observed Absolute Change From Baseline in LDL-C (mg/dl)(Baseline and 8 Weeks post-treatment)
- Observed Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)(Baseline and 8 Weeks post-treatment)
- Observed Absolute Change From Baseline in Non-HDL-C (mg/dL)(Baseline and 8 Weeks post-treatment)
- Observed Percent Change From Baseline in Total Cholesterol (TC)(Baseline and 8 Weeks post-treatment)
- Observed Absolute Change From Baseline in TC (mg/dL)(Baseline and 8 Weeks post-treatment)
- Observed Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)(Baseline and 8 Weeks post-treatment)
- Observed Absolute Change From Baseline in hsCRP (mg/L)(Baseline and 8 Weeks post-treatment)
- Acceptability of Taste of Liquid Formulation Using a Dosing Acceptability Questionnaire(Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16)
- Acceptability of Ease of Swallowing Tablet Formulation Using a Dosing Acceptability Questionnaire(Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16)
- Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs(Up to Week 16)