A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Number of Participants Who Incurred at Least One Treatment Emergent Event
研究概览
简要总结
The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.
The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.
AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Single Ascending Dose (SAD) Study:
- •Male or female non-smoker, ≥18 and ≤55 years of age, with BMI >18.5 and < 32.0 kg/m²
- •Total cholesterol greater or equal to 5.0 mmol/L (≥194 mg/dL) at screening
- •Multiple Ascending Dose (MAD) Study:
- •Male or female non-smoker, ≥18 and ≤75 years of age, with BMI >18.5 and < 35.0 kg/m²
- •Diagnosis of refractory hypercholesterolemia with LDL cholesterol levels > 2.5 mmol/L (97 mg/mL) at screening.
- •On stable lipid lowering therapy for ≥ 8 weeks
- •On stable diet for ≥ 12 weeks.
排除标准
- •Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
- •History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
- •Significant health problems within 6 months prior to screening, which in the opinion of the Medical Sub-Investigator would prevent the subject from participating in the study, including but not limited to: unstable coronary heart disease; transient ischemic attack; stroke; revascularization procedure; uncontrolled hyperthyroidism; coagulation disorder; peptic ulcers or GI bleeding; significant disease of the central nervous system; liver or renal disease.
- •History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
研究组 & 干预措施
AEM-28
Single Ascending Dose: Single IV dose for each cohort; dose range 0.032 mg/mL to 3.54 mg/mL
Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks; dose range 1 mg/kg to 3.54 mg/kg.
干预措施: AEM-28 (Drug)
Normal Saline
Single Ascending Dose: Single IV dose for each cohort.
Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks.
干预措施: Normal Saline (Drug)
结局指标
主要结局
Number of Participants Who Incurred at Least One Treatment Emergent Event
时间窗: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
Number of Participants Who Incurred Mild Treatment Emergent Adverse Events
时间窗: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
Number of Participants Who Incurred Moderate Treatment Emergent Events
时间窗: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
次要结局
- Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change(Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57)