A Randomised, Double-blind, Placebo-controlled Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone Stimulation Test Following Treatment With Baxdrostat for 8 Weeks in Participants With Uncontrolled Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test
研究概览
简要总结
The main purpose of this study is to assess the serum free cortisol response after ACTH stimulation test at baseline and at Week 8 in participants with uncontrolled hypertension.
详细描述
This is a placebo-controlled study to evaluate cortisol reserve after ACTH stimulation test following treatment with 2 milligrams (mg) baxdrostat versus placebo.
The study consists of 3 period:
- 4-week screening period.
- An 8-week double-blind treatment period.
- A safety follow-up 2 weeks after last dose.
Participants will be randomized in a 2:1 ratio to one of 2 treatment arms:
- Baxdrostat
- Placebo
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with mean seated systolic blood pressure (SBP) on automated office blood pressure measurement (AOBPM) greater than equal to (>=) 130 millimeter of mercury (mmHg) and less than (<) 170 mmHg at screening.
- •Participants with mean seated SBP on AOBPM of >=130 mmHg and < 170 mmHg at randomization.
- •Participants must have a stable regimen of >=1 antihypertensive medication (at least one should be a diuretic), for at least 4 weeks prior to screening.
- •Participants must have an estimated glomerular filtration rate (eGFR) >=45 milliliter per minute (mL/min)/1.73-meter square (m^²) at screening.
- •Participants must have a serum potassium+ (K+) level >=3.5 and < 5.0 millimole per liter (mmol/L) at screening.
排除标准
- •Mean seated diastolic blood pressure (DBP) on AOBPM >=110 mmHg at randomization.
- •Prior treatment (within the 4 weeks before screening) with angiotensin receptor Blocker (ARBs) and angiotensin converting enzyme inhibitor (ACEIs) (both taken simultaneously).
- •Serum sodium (Na+) level < 135 millimole per liter (mmol/L) at screening, determined as per central laboratory.
- •New York heart association functional heart failure (HF) Class IV at screening.
- •Planned percutaneous coronary intervention/coronary artery bypass grafting or percutaneous coronary intervention/coronary artery bypass grafting done within 6 months prior to screening.
- •Uncontrolled diabetes with glycated haemoglobin (HbA1c) > 10.0% (86 mmol/mol) at screening.
- •Fridericia's corrected QT (QTcF) value > 470 milliseconds (ms) at screening, unless having a pacemaker.
- •Heart rate < 45 or > 110 beats/min in a resting position, as per vital signs assessment.
研究组 & 干预措施
Arm 2: Placebo
Participants will receive placebo tablet orally once daily.
干预措施: Placebo (Drug)
Arm 1: Baxdrostat 2 mg
Participants will receive baxdrostat 2 mg tablet orally once daily.
干预措施: Baxdrostat (Drug)
结局指标
主要结局
Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test
时间窗: Week 8
The primary endpoint is individual participant's cortisol levels at each timepoint. Number of participants with normal stimulated serum total cortisol level at baseline are presented here. Characterisation of the serum total cortisol levels before and after ACTH stimulation test. An ACTH stimulation test using 250 μg ACTH was performed at baseline and Week 8 (End of Treatment), with serum cortisol level measured before and after ACTH stimulation test. Normal cortisol levels are defined as at least 18 μg/dL when measured 60 minutes (±10 minutes) after stimulation. If the Week 8 results show abnormal levels, a repeat test is conducted. In this repeat test, cortisol is considered abnormal only if both of the following conditions are met: the level is less than 14.8 μg/dL at 30 minutes (± 5 minutes) and less than 18 μg/dL at 60 minutes (±10 minutes).
次要结局
- Incidence of Abnormal Stimulated Cortisol at Week 8(Week 8)
- Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)(From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks))