KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Once-Daily LY3473329 in Adults With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 233
- 试验地点
- 42
- 主要终点
- Percent Change From Baseline in Lp(a) - Assessed Via Intact Lp(a) Assay
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy and safety of LY3473329 in adult participants with elevated Lp(a) at high risk for cardiovascular events.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be at least 40 years old
- •Participants with Lp(a) ≥175 nmol/L at randomization, measured at the central laboratory.
- •High risk for cardiovascular events defined as documented coronary artery disease (CAD), stroke, or peripheral artery disease or atherosclerotic cardiovascular disease (ASCVD) risk equivalents (familial hypercholesterolemia or type 2 diabetes).
- •Participants on the following medications according to local practice must be on a stable regimen for at least 4 weeks prior to randomization and expected to remain on a stable regimen through the end of the post-treatment follow-up period.
- •lipid-lowering drugs
- •testosterone, estrogens, anti-estrogens, progestins, selective estrogen receptor modulators, or growth hormone
- •Have a body mass index within the range 18.5 to 40 kilogram/square meter (kg/m²), inclusive.
- •Males who agree to use highly effective or effective methods of contraception may participate in this trial.
- •Women of childbearing potential (WOCBP) who agree to use highly effective or effective methods of contraception and women not of childbearing potential (WNOCBP) may participate in this trial.
排除标准
- •Have a history or presence of an underlying disease, or surgical, physical, medical, or psychiatric condition that, in the opinion of the investigator, would potentially affect participant safety within the study or interfere with participating in or completing the study or with the interpretation of data.
- •Any of the following, or other events indicating unstable medical condition in the opinion of the investigator, within 3 months of randomization:
- •major surgery
- •coronary, carotid, or peripheral arterial revascularization
- •stroke or transient ischemic attack
- •myocardial infarction or unstable angina
- •acute limb ischemia
- •Have, in the 6 months prior to day 1, uncontrolled Type 1 or Type 2 diabetes
- •Have uncontrolled hypertension
研究组 & 干预措施
10 mg LY3473329
Participants received 10 milligrams (mg) of LY3473329 administered orally once daily (QD) over a 12-week treatment period.
干预措施: LY3473329 (Drug)
60 mg LY3473329
Participants received 60 mg of LY3473329 administered orally QD over a 12-week treatment period.
干预措施: LY3473329 (Drug)
240 mg LY3473329
Participants received 240 mg of LY3473329 administered orally QD over a 12-week treatment period.
干预措施: LY3473329 (Drug)
Placebo
Participants received a matching dose of placebo administered orally QD over a 12-week treatment period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Lp(a) - Assessed Via Intact Lp(a) Assay
时间窗: Baseline, Week 12
Least Squares Mean (LS Mean) was calculated using a Mixed Model for Repeated Measures (MMRM): Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Treatment + Time + Treatment\*Time.
Percent Change From Baseline in Lp(a) - Assessed Via Apo(a) Assay
时间窗: Baseline, Week 12
LS Mean was calculated using a MMRM: Log (Actual Measurement/Baseline) = Log (Baseline) + Country + Treatment + Time + Treatment\*Time.
次要结局
- Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Intact Lp(a) Assay(Week 12)
- Percentage of Participants Who Achieved Lp(a) < 125 Nmol/L - Assessed Via Apo(a) Assay(Week 12)
- Percent Change From Baseline in Apolipoprotein B (ApoB)(Baseline, Week 12)
- Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline, Week 12)
- Pharmacokinetics (PK): Trough Concentrations (C-trough) of LY3473329(Week from randomization 1, 2, 8, 12: Pre-dose)