Trial Outcomes & Findings for 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 (NCT NCT06336356)

Last Updated: 2025-12-17

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Week 8

Results posted on

2025-12-17

Participant Flow

This study was conducted in 10 sites in the United States of America from 10-June-2024 to 04-Dec-2024. The analyses presented in this report are based on a clinical data cutoff date of 28 January 2025.

Participants who met all the inclusion and none of the exclusion criteria were enrolled in this study. All study assessments were performed as per the schedule of assessment.

Participant milestones

Participant milestones
Measure	Baxdrostat 2 mg Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo Participants received placebo as a tablet orally once daily.
Overall Study STARTED	32	16
Overall Study COMPLETED	30	16
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Baxdrostat 2 mg Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo Participants received placebo as a tablet orally once daily.
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow Up	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Baxdrostat 2 mg n=32 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo n=16 Participants Participants received placebo as a tablet orally once daily.	Total n=48 Participants Total of all reporting groups
Age, Continuous	64.1 Years STANDARD_DEVIATION 9.2 • n=6 Participants	66.1 Years STANDARD_DEVIATION 7.4 • n=5 Participants	64.8 Years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	17 Participants n=6 Participants	9 Participants n=5 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=6 Participants	7 Participants n=5 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=6 Participants	7 Participants n=5 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized White	20 Participants n=6 Participants	9 Participants n=5 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: The full analysis set included all randomized participants who received at least one dose of study intervention. Here, 'number of participants analyzed' and 'number analyzed' specifies participants evaluated for this outcome measure at specific timepoints.

Outcome measures

Outcome measures
Measure	Baxdrostat 2 mg n=26 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo n=15 Participants Participants received placebo as a tablet orally once daily.
Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test Abnormal Stimulated cortisol at Week 8	0 Participants	0 Participants
Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test Normal Stimulated cortisol at Week 8	26 Participants	15 Participants

SECONDARY outcome

Timeframe: Week 8

The secondary endpoint is the incidence of abnormal stimulated cortisol after ACTH stimulation test at Week 8. Incidence of normal stimulated serum total cortisol level at baseline are presented. 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). Participants who had abnormal cortisol levels at the start of the study (baseline) were not included in this analysis.

Outcome measures

Outcome measures
Measure	Baxdrostat 2 mg n=26 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo n=15 Participants Participants received placebo as a tablet orally once daily.
Incidence of Abnormal Stimulated Cortisol at Week 8 Abnormal Stimulated cortisol at Week 8	0 Participants	0 Participants
Incidence of Abnormal Stimulated Cortisol at Week 8 Normal Stimulated cortisol at Week 8	26 Participants	15 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)

Population: The full analysis set included all randomized participants who received at least one dose of study intervention.

Safety and tolerability of baxdrostat as compared with placebo was assessed. For this clinical study, AESIs include the following: hyperkalaemia, hyponatraemia and hypotension events that require medical intervention.

Outcome measures

Outcome measures
Measure	Baxdrostat 2 mg n=32 Participants Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo n=16 Participants Participants received placebo as a tablet orally once daily.
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any AE leading to discontinuation of IP	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any AE	10 Participants	6 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any SAE	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any SAE with outcome death	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any possibly related AE	6 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any possibly related SAE	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Any AESIs	1 Participants	0 Participants

Adverse Events

Baxdrostat 2 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Baxdrostat 2 mg n=32 participants at risk Participants received a baxdrostat 2 mg tablet orally once daily.	Placebo n=16 participants at risk Participants received placebo as a tablet orally once daily.
Gastrointestinal disorders Nausea	6.2% 2/32 • Number of events 2 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	0.00% 0/16 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Gastrointestinal disorders Vomiting	6.2% 2/32 • Number of events 2 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	0.00% 0/16 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/32 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Infections and infestations Nasopharyngitis	0.00% 0/32 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Immune system disorders Seasonal allergy	0.00% 0/32 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Nervous system disorders Dizziness	6.2% 2/32 • Number of events 2 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Nervous system disorders Headache	3.1% 1/32 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	12.5% 2/16 • Number of events 2 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Nervous system disorders Lethargy	3.1% 1/32 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Eye disorders Vision blurred	0.00% 0/32 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)
Vascular disorders Hypotension	3.1% 1/32 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)	6.2% 1/16 • Number of events 1 • From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks)

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No unpublished information may be disclosed without prior written approval from AstraZeneca.
Publication restrictions are in place

Restriction type: OTHER