A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,083
- 试验地点
- 368
- 主要终点
- Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
研究概览
简要总结
This is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications.
详细描述
This study is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications, one of which must be a thiazide or thiazide-like diuretic.
The study consists of a 2-week screening period with a 2-week single-blind run-in period followed by a 12-week randomized, double-blind, placebo-controlled, parallel arm period. Following the randomized period subjects will be offered an opportunity to participate in an open-label extension (OLE) study. Any subject electing to not participate in the OLE will undergo an end of study (EoS) visit, which will occur after end of treatment (EoT), to complete their participation in the study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age at the time of signing the informed consent form (ICF)
- •At Screening and Randomization: AOBP SBP of ≥135 and ≤180 mmHg plus AOBP DBP of ≥65 and ≤110 mmHg, or AOBP DBP of ≥90 and ≤110 mmHg
- •Taking between 2 and 5 AHT medications,
- •History of hypertension lasting at least 6 months prior to Screening
- •Body mass index (BMI) of ≥18 kg/m2 at Screening
排除标准
- •Women who are pregnant, plan to become pregnant, or are breastfeeding
- •Participation in a study involving any investigational device or small-molecule drug within 4 weeks or 6 months for biologic (antibody) drugs prior to the Screening Visit
- •eGFR <45 mL/min/1.73m2 at Screening, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- •Serum potassium >5.0 mmol/L at Screening or >4.8 mmol/L at Randomization
- •Serum sodium <135 mmol/L (corrected for hyperglycemia) at Screening.
- •History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to the Screening Visit.
研究组 & 干预措施
Placebo
Placebo once daily (QD) for 12 weeks
干预措施: Placebo (Drug)
Dose 1
50 mg lorundrostat Dose 1 once daily (QD) for 12 weeks
干预措施: lorundrostat Dose 1 (Drug)
Dose 2
50 mg lorundrostat Dose 1 once daily (QD) for 6 weeks then 100 mg lorundrostat Dose 2 once daily (QD) for 6 weeks for subjects who meet prespecified criteria
干预措施: lorundrostat Dose 2 (Drug)
结局指标
主要结局
Change from baseline in automated office BP (AOBP) SBP at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo
时间窗: Week 6
次要结局
- Change from baseline in AOBP SBP at Week 12 in subjects randomized to lorundrostat 50 mg QD with escalation to lorundrostat 100 mg QD compared to subjects randomized to placebo(Week 12)
- Proportion of subjects with AOBP SBP <130 mmHg at Week 6 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(Week 6)
- Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 2 prescribed AHT medications(Week 6)
- Change from baseline in AOBP SBP at Week 6 in subjects with uncontrolled hypertension on 3 or more prescribed AHT medications(Week 6)
- Change from baseline in AOBP SBP at Week 6 by obesity status in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(Week 6)
- Change from baseline in AOBP SBP at Week 12 in subjects who were escalated to lorundrostat 100 mg QD at week 6 (within-subjects analysis)(Week 12)