A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-4021586 in Adults With Symptomatic Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 49
- 主要终点
- Incidence of early drug discontinuation
研究概览
简要总结
This is a Phase 2 dose-finding study in adult participants with symptomatic HFpEF.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females ≥ 40 years and ≤ 85 years of age at screening.
- •Diagnosed with HF with NYHA functional class II or III.
- •Screening echocardiography with LVEF ≥ 60%.
- •Screening NT-proBNP ≥ 300 pg/mL for participants in sinus rhythm and ≥ 900 pg/mL for participants with comorbid atrial fibrillation or flutter.
- •Body mass index < 40 kg/m
- •Participants on beta-blockers, angiotensin-converting enzyme (ACE)/angiotensin II receptor blocker (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI), must be on stable doses for more than 30 days prior to screening.
- •Participants on a glucagon-like peptide-1 (GLP-1) agonist must be on a stable dose for more than 24 weeks prior to screening with no anticipated plans to change dose during this study.
排除标准
- •History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
CK-4021586 - Cohort 1
Participants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
干预措施: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg) (Drug)
CK-4021586 - Cohort 3
Participants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
干预措施: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg) (Drug)
Placebo - Cohort 3
Participants will receive placebo daily for up to 12 weeks.
干预措施: Placebo to match CK-4021586 (Drug)
Placebo - Cohort 1
Participants will receive placebo daily for up to 12 weeks.
干预措施: Placebo to match CK-4021586 (Drug)
CK-4021586 - Cohort 2
Participants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
干预措施: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg) (Drug)
Placebo - Cohort 2
Participants will receive placebo daily for up to 12 weeks.
干预措施: Placebo to match CK-4021586 (Drug)
结局指标
主要结局
Incidence of early drug discontinuation
时间窗: 12 weeks
Incidence of early drug discontinuation observed during dosing of CK 4021586 in patients with HFpEF
Incidence of LVEF < 40%
时间窗: 12 weeks
Incidence of left-ventricular ejection fraction (LVEF) \< 40% observed during dosing of CK-4021586 in patients with HFpEF
Incidence of AEs
时间窗: 12 weeks
Incidence of adverse events observed during dosing of CK-4021586 in patients with HFpEF
次要结局
- Change in NT-proBNP(Baseline to Week 6 and Week 12)
- Plasma concentrations of CK-4021586(12 weeks)
- Concentration-response relationship of CK-4021586 on NT-proBNP change(Baseline to Week 12)
- Concentration-response relationship of CK-4021586 to LVEF change(Baseline to Week 12)
- Change in LVEF(Baseline to Week 6 and Week 12)