A Phase IIb, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AZD0780 in Participants With Dyslipidemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 428
- 试验地点
- 1
- 主要终点
- Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12
研究概览
简要总结
The primary purpose of this study is to measure the effect of different daily doses of AZD0780 on Low-Density Lipoprotein (LDL-C) levels compared with placebo in participants with dyslipidemia. The effect of AZD0780 versus placebo on other lipid parameters and inflammatory markers is also investigated. The concentration of AZD0780 in blood at specific timepoints is measured, and the safety and tolerability of AZD0780 will be evaluated. There is a follow-up after end of treatment, but expanded access is not available. The primary hypothesis is that at least one of the investigated doses of AZD0780 is superior to placebo in lowering LDL-C level, in percent change from baseline up to week 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- 否
入选标准
- •Males, and females of non-childbearing potential 18 to 75 years of age, inclusive, at the time of signing the informed consent.
- •Participants with a fasting low-density lipoprotein cholesterol (LDL-C) higher than or equal to 70 mg/dL (1.8 mmol/L) and lower than 190 mg/dL (4.9 mmol/L) at screening.
- •Participants with fasting triglycerides lower than 400 mg/dL (lower than 4.52 mmol/L) at screening.
- •Should be receiving moderate or high-intensity statin therapy for more than or equal to 2 months prior to screening.
- •There should be no planned medication or dose change during study participation.
- •Body mass index at or above 19.0 kg/m^2.
排除标准
- •History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any uncontrolled or serious disease, or any medical (e.g., known major active infection or major hematological, renal, metabolic, gastrointestinal, respiratory, or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
- •Poorly controlled type 2 diabetes mellitus, defined as hemoglobin A1c (HbA1c) greater than 10 percent at screening.
- •Acute ischemic cardiovascular event in the last 12 months.
- •Heart failure with New York Heart Association (NYHA) Class III-IV.
- •Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
- •Recipient of any major organ transplant, e.g., lung, liver, heart, bone marrow, renal.
- •LDL or plasma apheresis within 12 months prior to randomization.
- •Uncontrolled hypertension.
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as judged by the investigator.
研究组 & 干预措施
Arm A
AZD0780, Dose 1
干预措施: AZD0780 (Drug)
Arm E
Placebo, matched for appearance
干预措施: Placebo (Drug)
Arm D
AZD0780, Dose 4
干预措施: AZD0780 (Drug)
Arm C
AZD0780, Dose 3
干预措施: AZD0780 (Drug)
Arm B
AZD0780, Dose 2
干预措施: AZD0780 (Drug)
结局指标
主要结局
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12
时间窗: From first day of treatment up to week 12
Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C \* 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
次要结局
- Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Total Cholesterol at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Triglycerides at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Apolipoprotein A1 at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Apolipoprotein B at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Lipoprotein-a at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of Remnant Cholesterol at Week 12(From first day of treatment up to week 12)
- Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12(From first day of treatment up to week 12)
- AZD0780 Plasma Concentrations Summarized by Sampling Timepoint(From week 1 up to week 12)