A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 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, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 (zilebesiran) in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of >130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and >135 and ≤165 mmHg without hypertensive medication for Part E
- •Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m^2; Part D: Has BMI >35 and ≤50 kg/m^2; Part E: Has BMI ≥18 kg/m^2 and ≤50 kg/m^2
- •Has a normal 12-lead electrocardiogram (ECG)
- •Is a nonsmoker
排除标准
- •Has secondary hypertension
- •Has orthostatic hypotension
- •Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
- •Recently received an investigational agent
- •Has diabetes mellitus
- •Has history of any cardiovascular event
- •Has history of intolerance to SC injection(s)
研究组 & 干预措施
Part A: SAD: ALN-AGT01
Participants will be administered a single dose of ALN-AGT01.
干预措施: ALN-AGT01 (Drug)
Part A: SAD: ALN-AGT01-Matching Placebo
Participants will be administered a single dose of ALN-AGT01-matching placebo.
干预措施: ALN-AGT01-Matching Placebo (Drug)
Part B: SD: ALN-AGT01
Participants with controlled salt intake will be administered a single dose of ALN-AGT01.
干预措施: ALN-AGT01 (Drug)
Part B: SD: ALN-AGT01-Matching Placebo
Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo.
干预措施: ALN-AGT01-Matching Placebo (Drug)
Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
干预措施: ALN-AGT01 (Drug)
Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
干预措施: Irbesartan-Matching Placebo (Drug)
Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
干预措施: ALN-AGT01-Matching Placebo (Drug)
Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
干预措施: Irbesartan (Drug)
Part E: Open Label: ALN-AGT01 + Irbesartan
Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.
干预措施: ALN-AGT01 (Drug)
Part E: Open Label: ALN-AGT01 + Irbesartan
Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.
干预措施: Irbesartan (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months
次要结局
- Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites(Parts A, B and E: Up to Day 15; Part D: Up to Day 99)
- Change from Baseline in Blood Angiotensinogen (AGT) Level(Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months)
- Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites(Parts A, B and E: Up to Day 15; Part D: Up to Day 99)