A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Medication Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 285
- 试验地点
- 103
- 主要终点
- Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)
研究概览
简要总结
A Phase 2 trial to evaluate the blood pressure-lowering effect of lorundrostat an aldosterone synthase inhibitor (ASI), administered as an add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.
详细描述
This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an ASI), administered as add-on to a standardized anti-hypertensive (AHT) medication regimen, in subjects with hypertension.
The study consists of a standardized AHT regimen run-in period followed by a randomized, double-blind, placebo-controlled, parallel arm period. Following the double-blind period subjects may be offered the opportunity to participate in an open-label extension (OLE) study. Subjects electing to not participate in the OLE will undergo an end of study (EoS) visit approximately 2 weeks after the last dose of study drug 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, Care Provider)
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
- •At Screening: AOBP SBP of 140-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg
- •24-hour average ABPM SBP of 130-180 mmHg or 24-hour average ABPM DBP >80 mmHg
- •Taking between 2 and 5 AHT medications, inclusive, at Screening visit.
- •BMI of 18-40 kg/m2 inclusive at Screening
排除标准
- •eGFR <45 mL/min/1.73 m2 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 at Screening
- •History of heart failure, myocardial infarction, stroke, or transient ischemic attack within 6 months prior to Screening.
- •Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening
研究组 & 干预措施
Placebo
Placebo once daily for 12 weeks
干预措施: Placebo (Drug)
Dose 1
lorundrostat Dose 1 once daily for 12 weeks
干预措施: lorundrostat Dose 1 (Drug)
Dose 2
lorundrostat Dose 1 once daily for 4 weeks then lorundrostat Dose 2 once daily for 8 weeks
干预措施: lorundrostat Dose 2 (Drug)
结局指标
主要结局
Change in 24-hour average ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP)
时间窗: Baseline (Randomization) to Week 12
次要结局
- Change from baseline in 24-hour average ABPM SBP at Week 4 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(Baseline to Week 4)
- Proportion of subjects with 24-hour average ABPM SBP <125 mmHg at Week 4 in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(at Week 4)
- Change from baseline in 24-hour average ABPM SBP at Week 4 by obesity status in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(Baseline to Week 4)
- Change from baseline in automated office BP (AOBP) SBP at Week 12 in subjects who were escalated to lorundrostat 100 mg QD at Week 4 (within-subjects analysis)(Baseline to Week 12)
- Change from baseline in 24-hour average ABPM SBP at Week 4, by number of AHT medications in the standardized AHT regimen (2 and 3) in subjects randomized to lorundrostat 50 mg QD compared to subjects randomized to placebo(Baseline to Week 4)
- Proportion of subjects with 24-hour average ABPM SBP <125 mmHg at Week 12 in subjects randomized to lorundrostat (by arm and pooled dosages) compared to subjects randomized to placebo(Baseline to Week 12)
- Change from baseline in 24-hour average ABPM SBP at Week 12 by obesity status in subjects randomized to lorundrostat (by arm and pooled dosages) compared to subjects randomized to placebo(Baseline to Week 12)
- Change from baseline in daytime average ABPM SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placebo(Baseline to Week 4 and Week 12)
- Change from baseline in AOBP SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg QD (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placebo(Baseline to Week 4 and Week 12)
- Change from baseline in nighttime average ABPM SBP at Week 4 and Week 12 in subjects randomized to lorundrostat 50 mg QD (Week 4) and by arm and pooled dosages (Week 12) compared to subjects randomized to placebo(Baseline to Week 4 and Week 12)
- Change from baseline in 24-hour average ABPM SBP at Week 12, in subjects randomized to lorundrostat (pooled dosages) compared to subjects randomized to placebo(Baseline to Week 12)