A Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone (ACTH) Stimulation Test Following Baxdrostat Treatment Compared to Placebo in Participants With Uncontrolled Hypertension

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

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.

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:

1. Baxdrostat
2. Placebo

Participants will receive either baxdrostat or placebo.

The overall study duration will be up to 16 weeks.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.