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

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Uncontrolled Hypertension

Treatments: Drug: Placebo; Drug: Baxdrostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT06336356

D6970C00011

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

48 participants in 2 patient groups, including a placebo group

Arm 1: Baxdrostat 2 mg

Experimental group

Description:

Participants will receive baxdrostat 2 mg tablet orally once daily.

Treatment:

Drug: Baxdrostat

Arm 2: Placebo

Placebo Comparator group

Description:

Participants will receive placebo tablet orally once daily.

Treatment:

Drug: Placebo