A Multi-center, Randomized, Participant- and Investigator- Blinded, Placebo-controlled Crossover Study to Investigate the Safety, Tolerability, and Pharmacokinetics of HJB647 in Participants With Chronic Stable Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Number of participants with Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of HJB647 at two different doses in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).
详细描述
This is a multi-center, randomized, participant- and investigator- blinded, placebo- controlled crossover study to investigate the safety, tolerability, and pharmacokinetics of HJB647 in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).
The study will consist of approximately 12 participants randomly assigned in a 1:1:1 ratio to one of three 3-day treatment sequences comprised of two doses of HJB647 and placebo. Dosing of the HJB647 and placebo is planned for 3 consecutive days. Participants will be domiciled during study drug administration period for close monitoring with a follow-up in-clinic visit on Day 7. A safety call will be performed on Day 33.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants eligible for inclusion in this study must meet all of the following criteria:
- •Men and women aged 18 years or older
- •Stable NYHA functional class II-III
- •LVEF <50%
- •NT-proBNP ≥600 pg/ml if in sinus rhythm or ≥900 pg/ml if in atrial fibrillation at screening
- •On stable standard of care therapy with sacubitril/valsartan with a dose of at least 49/51 mg BID for at least 4 weeks before screening.
排除标准
- •Participants will be deemed ineligible for inclusion if they meet any of the following exclusion criteria:
- •Acute decompensated heart failure within 3 months prior to screening
- •SBP <105 mmHg at screening or baseline.
- •Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
- •Hemodynamically significant mitral and/or aortic valve disease, or any prior valve replacement, except mitral regurgitation secondary to LV dilation at screening
- •eGFR <30 ml/min/1.73m2 at screening, as measured by the CKD-EPI formula
- •BMI >40 kg/m2
- •Strong CYP3A4 inhibitors or inducers, sGC activators (vericiguat), PDE5 inhibitors, and nitroglycerin products
- •Women of childbearing potential
- •Further eligibility criteria might apply in alignment with the trial protocol.
研究组 & 干预措施
Placebo
Taken by mouth as capsules
干预措施: Placebo (Other)
HJB647 low dose
Taken by mouth as capsule
干预措施: HJB647 low dose (Drug)
HJB647 high dose
Taken by mouth as capsule
干预措施: HJB647 high dose (Drug)
结局指标
主要结局
Number of participants with Adverse Events (AEs)
时间窗: Up to 33 days
Number of participants with AEs as a measure of safety and tolerability
Number of participants with clinically significant changes in vital signs
时间窗: Up to 33 days
Number of participants with clinically significant changes in Systolic Blood Pressure, Diastolic Blood Pressure, Heart Rate, Electrocardiogram and hyposensitive events as a measure of adverse events
次要结局
- Pharmacokinetics: Maximum concentration (Cmax)(Up to 7 days)
- Pharmacokinetics: Time to reach maximum plasma concentration (Tmax)(Up to 7 days)
- Pharmacokinetics: Area Under the Concentration-Time Curve from dosing form to the last measurable concentration (AUClast)(Up to 7 days)