A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously for 8 Weeks to Hypertensive Subjects With Uncontrolled Blood Pressure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 9
- 主要终点
- Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo
研究概览
简要总结
This study evaluated the effect of ISIS 757456 (IONIS-AGT-LRx) on plasma angiotensinogen (AGT) and systolic blood pressure (SBP) in uncontrolled hypertensive participants who were on two to three antihypertensive medications.
详细描述
This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion
- •History of secondary hypertension (HTN)
- •The use of the following at time of screening and during the course of the study:
- •Other medications for the treatment of HTN (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)
- •Medications that may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
- •Oral or SC anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox)
- •Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol)
- •Phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil)
- •Potassium-sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene)
- •Unstable/underlying cardiovascular disease defined as:
- •Any history of congestive heart failure (New York Heart Association [NYHA] class II-IV)
- •Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening
- •12-lead electrocardiogram (ECG) corrected using Fridericia's formula (QTcF) > 450 milliseconds (msec) in males and > 470 msec in females at screening, or a history or evidence of long QT syndrome
- •Any clinically significant active atrial or ventricular arrhythmias
- •Any history of coronary bypass or percutaneous coronary intervention
研究组 & 干预措施
Placebo
Participants received ISIS 757456-matching placebo, subcutaneous (SC) injection, once-weekly for 8 weeks and an additional loading dose on Day 3.
干预措施: Placebo (Drug)
ISIS 757456
Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3.
干预措施: ISIS 757456 (Drug)
结局指标
主要结局
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo
时间窗: Baseline up to Day 57 (start of Week 9)
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
次要结局
- Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit(Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141)
- Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit(Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141)
- Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit(Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141)