A Phase 1b, Randomized, Participant- and Investigator- Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HJB647 Following Single Ascending Dose and Up-titration Multiple Dose Administration in Japanese Healthy Participants With Elevated Blood Pressure and Patients With Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 1
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacokinetics, and pharmacodynamics of HJB647 following single dose administration in Japanese healthy participants with elevated blood pressure and multiple dose administration with up titration in Japanese patients with hypertension, to support future clinical development of HJB647
详细描述
Randomized, placebo-controlled, participant- and investigator-blind study consisting of two parts:
- Part 1 (SAD part): Single oral dose in healthy participants. Sentinel dosing will be applied in each cohort.
- Part 2 (MAD part): Multiple oral doses in patients with hypertension. Safety reviews will guide dose escalation and up-titration.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Japanese healthy participants with elevated blood pressure (Part 1) and patients with mild-to-moderate hypertension (Part 2)
- •Age: 18 to 55 years (Part 1) and 18 to 60 years (Part 2)
- •Body weight:
- •Male: ≥ 50.0 kg
- •Female: ≥ 45.0 kg
- •Body Mass Index (BMI): 18.0 to 30.0 kg/m²
- •Axillary body temperature: 35.0-37.5 °C
- •Heart rate: 50-90 bpm
- •Blood pressure criteria are as follows:
- •Part 1: Healthy Participants with Elevated Blood Pressure Screening: Systolic Blood Pressure (SBP): 120 ≤ SBP ≤ 139 mmHg; Diastolic Blood Pressure (DBP): 60 ≤ DBP ≤ 94 mmHg Baseline (Day -1): SBP: 120 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg
- •Part 2: Patients with Hypertension Screening and Baseline (Day -1): SBP: 140 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg
排除标准
- •Significant illness, including infectious diseases that have not resolved within 30 days prior to baseline
- •History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:
- •Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker.
- •History of familial long QT syndrome or known family history of Torsades de Pointes
- •Resting QT interval corrected by Fridericia's formula (QTcF) ≥ 450 msec (male) or ≥ 460 msec (female) at screening
- •At screening, hypokalemia or hypomagnesemia defined as potassium or magnesium values below the LLN on repeat measurement, or laboratory abnormalities indicating hypothyroidism, as determined at the discretion of the investigator
- •HbA1c ≥ 7.0% or LDL cholesterol ≥ 180 mg/dL or triglycerides ≥ 250 mg/dL
- •Use of any prescription drugs or herbal supplements within 4 weeks prior to initial dosing, and/or OTC medication or dietary supplements (vitamins included) within 2 weeks prior to initial dosing
- •Women of childbearing potential
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Part 2-1: HJB647 multiple oral doses
Multiple oral doses of HJB647 with adaptive up-titration in Part 2
干预措施: HJB647 (Drug)
Part 2-2: HJB647 multiple oral doses (optional cohort)
Multiple oral doses of HJB647 with adaptive up-titration in Part 2
干预措施: HJB647 (Drug)
Part 1-1: HJB647 low dose
Single dose Day 1 in Part 1
干预措施: HJB647 (Drug)
Part 1-2: HJB647 mid-dose
Single dose Day 1 in Part 1
干预措施: HJB647 (Drug)
Part 1-3: HJB647 high dose
Single dose Day 1 in Part 1
干预措施: HJB647 (Drug)
Part 1: Placebo
Single dose Day 1 in Part 1
干预措施: Placebo (Drug)
Part 2-3: HJB647 multiple oral doses (optional cohort)
Multiple oral doses of HJB647 with adaptive up-titration in Part 2
干预措施: HJB647 (Drug)
Part 2-4: HJB647 multiple oral doses (optional cohort)
Multiple oral doses of HJB647 with adaptive up-titration in Part 2
干预措施: HJB647 (Drug)
Part 2-5: HJB647 multiple oral doses (optional cohort)
Multiple oral doses of HJB647 with adaptive up-titration in Part 2
干预措施: HJB647 (Drug)
Part 2: Placebo
Multiple oral doses of placebo with adaptive up-titration in Part 2
干预措施: Placebo (Drug)
结局指标
主要结局
未指定
次要结局
- Part 2: Office blood pressure change from baseline(Baseline to Day 27 of part 2)
- Part 2: Heart rate change from baseline(Baseline to Day 27 of part 2)
- Part 1: Number of participants with AEs(Up to 31 days)