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

Phase 2

Completed

• Conditions: Uncontrolled Hypertension
• Interventions: Drug: Baxdrostat; Drug: Placebo

• Registration Number: NCT06336356
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-03-22
• Study First Submitted QC: 2024-03-22
• Study First Posted: 2024-03-28
• Study Start: 2024-06-10
• Status Verified: 2024-12
• Primary Completion: 2024-12-04
• Study Completion: 2024-12-04
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Baxdrostat 2 mg	Baxdrostat	Participants will receive baxdrostat 2 mg tablet orally once daily.
Arm 2: Placebo	Placebo	Participants will receive placebo tablet orally once daily.

Primary Outcome Measures

Name	Time	Method
Individual Cortisol Level	At baseline and Week 8	The serum free cortisol response before and after ACTH stimulation test will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Abnormal Stimulated Cortisol	At Week 8	Total abnormal serum cortisol response after ACTH stimulation test at Week 8 will be evaluated.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Norfolk, Virginia, United States