Uncontrolled Hypertension
Conditions
Keywords
Adrenocorticotropic hormone stimulation
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.
Interventions
DRUGBaxdrostat
Baxdrostat will be administered orally once daily.
DRUGPlacebo
Placebo will be administered orally once daily.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test | Week 8 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Abnormal Stimulated Cortisol at Week 8 | 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. |
| Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | From Day 1 up to Week 8 or Safety follow-up (14 days post last dose), which ever comes first (up to 10 weeks) | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Baxdrostat 2 mg Participants received a baxdrostat 2 mg tablet orally once daily. | 32 |
| Placebo Participants received placebo as a tablet orally once daily. | 16 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow Up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Baxdrostat 2 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.1 Years STANDARD_DEVIATION 9.2 | 66.1 Years STANDARD_DEVIATION 7.4 | 64.8 Years STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 7 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 9 Participants | 29 Participants |
| Sex: Female, Male Female | 17 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 16 |
| other Total, other adverse events | 6 / 32 | 6 / 16 |
| serious Total, serious adverse events | 0 / 32 | 0 / 16 |
Outcome results
Primary
Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Baxdrostat 2 mg | Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test | Abnormal Stimulated cortisol at Week 8 | 0 Participants |
| Baxdrostat 2 mg | Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test | Normal Stimulated cortisol at Week 8 | 26 Participants |
| Placebo | Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test | Abnormal Stimulated cortisol at Week 8 | 0 Participants |
| Placebo | Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test | Normal Stimulated cortisol at Week 8 | 15 Participants |
Secondary
Incidence of Abnormal Stimulated Cortisol at 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Baxdrostat 2 mg | Incidence of Abnormal Stimulated Cortisol at Week 8 | Abnormal Stimulated cortisol at Week 8 | 0 Participants |
| Baxdrostat 2 mg | Incidence of Abnormal Stimulated Cortisol at Week 8 | Normal Stimulated cortisol at Week 8 | 26 Participants |
| Placebo | Incidence of Abnormal Stimulated Cortisol at Week 8 | Abnormal Stimulated cortisol at Week 8 | 0 Participants |
| Placebo | Incidence of Abnormal Stimulated Cortisol at Week 8 | Normal Stimulated cortisol at Week 8 | 15 Participants |
Secondary
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any SAE with outcome death | 0 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any possibly related AE | 6 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any SAE | 0 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any possibly related SAE | 0 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AE leading to discontinuation of IP | 1 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AESIs | 1 Participants |
| Baxdrostat 2 mg | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AE | 10 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AESIs | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AE | 6 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any SAE | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any SAE with outcome death | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any AE leading to discontinuation of IP | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any possibly related AE | 3 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | Any possibly related SAE | 0 Participants |