A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy and Safety of Baxdrostat in Adult Participants With Primary Aldosteronism
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 250
- 试验地点
- 89
- 主要终点
- Achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) at week 8.
研究概览
简要总结
This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, and efficacy of baxdrostat versus placebo, on the reduction of Seated Blood Pressure (SBP) and achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) in approximately 250 participants ≥ 18 years of age with Primary Aldosteronism (PA), with or without prior treatment with Mineralocorticoid Receptor Antagonists (MRAs) or potassium-sparing diuretics.
Baxdrostat (or placebo) will be administered once daily, up-titrated after 2 weeks based on clinical response and tolerability.
The study is planned to be conducted globally in approximately 90 study centres and 12 countries.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants must be ≥ 18 years of age
- •Participants with a documented diagnosis of PA that fulfils the criteria defined in the 2016 or 2025 Endocrine Society Guidelines.
- •Participants willing and able to cease dosing of MRA or potassium sparing diuretics per study requirement for participants taking an MRA or potassium sparing diuretic at Screening.
- •eGFR ≥ 45 mL/min/1.73m2 at Screening
- •Serum potassium level ≥ 3.0 and < 5.0 mmol/L at Screening determined as per the central laboratory.
- •Have a stable regimen of antihypertensive medications for at least 4 weeks prior to randomisation
- •Mean seated SBP on AOBPM of ≥ 135 mmHg and ≤ 170 mmHg and mean DBP of
- •≤ 105 mmHg.
- •Serum potassium (local lab) > 3.0 mmol/L at randomization.
排除标准
- •- If not taking an MRA or potassium sparing diuretic at Screening: Mean seated SBP > 170 mmHg or mean seated DBP >105 mmHg (on AOBPM).
- •If taking an MRA or potassium sparing diuretic at Screening: Mean seated SBP > 160 mmHg or mean seated DBP ≥ 100 mmHg.
- •Previous surgical intervention for an adrenal adenoma or have a planned adrenalectomy, renal nerve denervation, or adrenal ablative procedure during the course of the study.
- •Has the following known secondary causes of HTN: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation.
- •Serum sodium level < 135 mmol/L at Screening, determined as per central laboratory.
- •New York Heart Association functional HF class IV at Screening.
- •Persistent atrial fibrillation.
- •Treatment with any MRA or potassium-sparing diuretic within 2 weeks prior to Randomisation.
研究组 & 干预措施
Placebo
Matching placebo administered orally, once daily (QD).
干预措施: Placebo (Drug)
Baxdrostat
Baxdrostat administered orally, once daily (QD).
干预措施: Baxdrostat (Drug)
结局指标
主要结局
Achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) at week 8.
时间窗: At week 8
To assess the effect of baxdrostat vs placebo on achieving normalization of renin at week 8
Change from baseline in seated Systolic Blood Pressure (SBP) at Week 8
时间窗: At week 8
To assess the effect of baxdrostat versus placebo on seated Systolic Blood Pressure (SBP) at Week 8
次要结局
- Percent change from RWD baseline (Week 44) in Direct Renin Concentration (DRC) at Week 52(At week 52)
- Achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) at week 8.(At week 8)
- Change from Randomised withdrawal (RWD) baseline (Week 44) in seated Systolic Blood Pressure (SBP) at Week 52(At week 52)
- Achieving 24-hour urine aldosterone < 10 μg at Week 8 in participants with 24-hour urine aldosterone ≥ 10 μg at baseline(At week 8)
- Percent change from baseline in 24-hour urine albumin at Week 8(At week 8)
- Achieving serum potassium ≥ 3.7 mmol/L without potassium supplementation at Week 8 in participants with serum potassium < 3.7 mmol/L or potassium supplementation at baseline(At week 8)