Uncontrolled Hypertension, Resistant Hypertension
Conditions
Keywords
Hypertension, Uncontrolled hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase
Brief summary
This is a Phase III, multicentre, randomised, double-blinded, placebo-controlled, parallel group study to evaluate the safety, tolerability and effect of 1 or 2 mg baxdrostat versus placebo, administered once daily (QD) orally, on the reduction of systolic blood pressure in approximately 720 participants aged ≥ 18 years with hypertension, despite a stable regimen of 2 antihypertensive agents at baseline, one of which is a diuretic (uncontrolled hypertension); or ≥ 3 antihypertensive agents at baseline, one of which is a diuretic (treatment-resistant hypertension).
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD). Unit dose strengths: * 1 mg per tablet for 1 mg baxdrostat Arm; * 2 mg per tablet for 2 mg baxdrostat Arm.
DRUGPlacebo
Placebo tablet matching baxdrostat, administered orally, once daily (QD).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants must be ≥ 18 years old * Mean sitting systolic blood pressure on automated office blood pressure measurement ≥ 140 mmHg and \< 170 mmHg at Screening * Fulfil at least 1 of the following 2 criteria: 1. uHTN subpopulation: have a stable regimen of 2 antihypertensive medications, from different therapeutic classes (at least one must be a diuretic), at maximum tolerated dose in the judgement of the Investigator 2. rHTN subpopulation: have a stable regimen of ≥ 3 antihypertensive medications, from different therapeutic classes (at least one must be a diuretic), at maximum tolerated dose in the judgement of the Investigator * Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2 at Screening * Serum potassium (K+) level ≥ 3.5 and \< 5.0 mmol/L at Screening * Randomisation Criterion: * Sitting systolic blood pressure on attended automated office blood pressure measurement of ≥ 135 mmHg at the Baseline Visit
Exclusion criteria
* Mean sitting systolic blood pressure on attended automated office blood pressure measurement ≥ 170 mmHg * Mean seated diastolic blood pressure on attended automated office blood pressure measurement ≥ 110 mmHg * Serum sodium level \< 135 mmol/L at Screening * Has the following known secondary causes of hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation * New York Heart Association functional heart failure class IV at Screening * Persistent atrial fibrillation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Seated Systolic Blood Pressure for 2 mg Baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed. |
| Change From Baseline in Seated Systolic Blood Pressure for 1 mg Baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomised Withdrawal Baseline (Week 24) in Seated Systolic Blood Pressure (SBP) for 2 mg Baxdrostat | At Week 32 | To assess the effect of 2 mg baxdrostat vs placebo on seated systolic blood pressure (SBP) at 8 weeks after randomised withdrawal (RWD). All available measurements were included, and missing data were multiply imputed. |
| Change From Baseline in Seated SBP for 2 mg Baxdrostat in the Resistant Hypertension Subpopulation | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed. |
| Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 2 mg Baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed. |
| Number of Participants Who Achieved Seated SBP < 130 mmHg for 2 mg Baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed. |
| Change From Baseline in Seated SBP for 1 mg Baxdrostat in the Resistant Hypertension Subpopulation | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed. |
| Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 1 mg Baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed. |
| Number of Participants Who Achieved Seated SBP < 130 mmHg for 1 mg Baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Recruitment details
The study was done from 22 November 2023 to 05 November 2025. Participants were screened and randomised from 269 study sites across 29 countries. A total of 794 participants were randomised and treated in the study.
Pre-assignment details
Participants were screened for eligibility and entered a 2-week single-blind placebo run-in period. Both cohorts (Cohort 1 \[C1\] and Cohort 2 \[C2\]) completed a 12-week double-blind period (baxdrostat 2 mg, 1 mg, or placebo, 1:1:1) and a 12-week open-label period (baxdrostat 2 mg or standard of care). C1 participants on baxdrostat 2 mg at Week 24 also completed an 8-week randomised withdrawal period and a 20-week open-label extension; those on standard of care continued through Week 52.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.8 Years STANDARD_DEVIATION 11.7 |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 27 Participants |
| Race/Ethnicity, Customized Ethnicity : Missing | 10 Participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 231 Participants |
| Race/Ethnicity, Customized Race : American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race : Asian | 72 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 59 Participants |
| Race/Ethnicity, Customized Race : Missing | 6 Participants |
| Race/Ethnicity, Customized Race : Multiple | 2 Participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race : Other | 1 Participants |
| Race/Ethnicity, Customized Race : White | 500 Participants |
| Seated Systolic Blood Pressure | 149.3 mmHg STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 264 | 0 / 266 | 1 / 264 | 0 / 172 | 0 / 85 | 0 / 466 | 1 / 208 | 0 / 73 | 0 / 47 | 0 / 62 | 0 / 29 |
| other Total, other adverse events | 38 / 264 | 55 / 266 | 29 / 264 | 28 / 172 | 8 / 85 | 120 / 466 | 32 / 208 | 32 / 73 | 9 / 47 | 24 / 62 | 6 / 29 |
| serious Total, serious adverse events | 5 / 264 | 9 / 266 | 7 / 264 | 4 / 172 | 0 / 85 | 32 / 466 | 13 / 208 | 9 / 73 | 5 / 47 | 3 / 62 | 1 / 29 |
Outcome results
None listed