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.

Study Overview

• Status: Not yet recruiting
• Conditions: Uncontrolled Hypertension
• Intervention / Treatment: Drug: Baxdrostat; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Baxdrostat 2 mg; Participants will receive baxdrostat 2 mg tablet orally once daily.	Drug: Baxdrostat; Baxdrostat will be administered orally once daily.; Other Names: CIN-107; RO6836191,
Placebo Comparator: Arm 2: Placebo; Participants will receive placebo tablet orally once daily.	Drug: Placebo; Placebo will be administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual Cortisol Level	The serum free cortisol response before and after ACTH stimulation test will be evaluated.	At baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Abnormal Stimulated Cortisol	Total serum cortisol response after ACTH stimulation test at Week 8 will be evaluated.	At Week 8

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): May 13, 2024
• Primary Completion (Estimated): November 5, 2024
• Study Completion (Estimated): November 5, 2024

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Adrenocorticotropic hormone stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: D6970C00011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via there quest portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No