A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered QCZ484 in Healthy Subjects and Subjects With Mild Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 4
- 主要终点
- Number of participants with abnormalities in any laboratory parameter
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled study including Part A single ascending dose (SAD) in healthy subjects and Part B single dose in subjects with mild hypertension.
详细描述
Phase 1, multicenter, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of QCZ484. In Part A, single ascending doses of QCZ484 are tested in healthy subjects, while in Part B, single doses of QCZ484 are tested in subjects with mild hypertension. One dose of QCZ484 is administered subcutaneously.
This study was started by Argo Biopharma, and global sponsorship was transferred to Novartis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or females aged 18 to 60 years, inclusive, at the time of informed consent. (Part A only).
- •Males or females aged 18 to 72 years, inclusive, at the time of informed consent (Part B only).
- •Body mass index (BMI) >= 18 and <= 32 kg/m2 and body weight >50 kg (Part A only).
- •Body mass index (BMI) >=18 and <=35 kg/m2 and body weight >50 kg (Part B only).
- •Triplicate 12-lead electrocardiogram (ECG) after >5 minutes resting without clinically significant findings at screening and Day -
- •Mean sitting systolic blood pressure (SBP) of >=130 and <160 mm Hg (Part B only).
排除标准
- •History of hypotension or orthostatic hypotension.
- •History of syncope within 1 year.
- •SBP <90 mmHg or DBP <60 mm Hg at screening (Part A only).
- •Clinical laboratory findings outside of range are deemed clinically significant by the investigator at screening.
- •Any liver function panel analyte value > 1.2 ×upper limits of normal (ULN) at screening.
研究组 & 干预措施
Part A: QCZ484 600 mg
Healthy Cohort: single dose
干预措施: QCZ484 (Drug)
Part A: QCZ484 Placebo
Healthy Cohort: single dose
干预措施: Placebo (Drug)
Part B: QCZ484 600 mg
Hypertension Cohort: single dose
干预措施: QCZ484 (Drug)
Part B: QCZ484 300 mg
Hypertension Cohort: single dose
干预措施: QCZ484 (Drug)
Part A: QCZ484 150 mg
Healthy Cohort: single dose
干预措施: QCZ484 (Drug)
Part B: QCZ484 Placebo
Hypertension Cohort: single dose
干预措施: Placebo (Drug)
Part A: QCZ484 300 mg
Healthy Cohort: single dose
干预措施: QCZ484 (Drug)
Part A: QCZ484 50 mg
Healthy Cohort: single dose
干预措施: QCZ484 (Drug)
Part B: QCZ484 150 mg
Hypertension Cohort: single dose
干预措施: QCZ484 (Drug)
结局指标
主要结局
Number of participants with abnormalities in any laboratory parameter
时间窗: Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose
Safety laboratory data (blood chemistry, hematology, coagulation, and urinalysis)
Number of adverse events (AEs)
时间窗: Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose.
Overall number of AEs, severity, and relationship to study treatment per treatment group.
次要结局
- Plasma pharmacokinetics of QCZ484 - T1/2(Day 1; up to Day 8)
- Number of AEs(up to 48 weeks post dose)
- Number of participants with abnormalities in any laboratory parameter(up to 48 weeks post dose)
- Plasma pharmacokinetics of QCZ484 and metabolites - Cmax(Day 1; up to Day 8)
- Plasma pharmacokinetics of QCZ484 - Tmax(Day 1; up to Day 8)
- Plasma pharmacokinetics of QCZ484 and metabolites - AUC0-48(Day 1; up to Day 8)
- Urine pharmacokinetics of QCZ484(Day 1; up to Day 2)
- Plasma pharmacokinetics of QCZ484 - AUC0-inf(Day 1; up to Day 8)
- Change from baseline in serum angiotensinogen (AGT) level(up to 48 weeks post dose)