Resistant Hypertension
Conditions
Keywords
Hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase, Aldosterone synthase inhibitor
Brief summary
This is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg Baxdrostat vs. placebo, administered QD orally, on the reduction of SBP, measured by average 24-hour ABPM in 212 participants with rHTN (defined as seated SBP ≥ 140 mmHg at Screening and mean ambulatory SBP ≥ 130 mmHg at baseline, despite a stable regimen of ≥ 3 antihypertensive agents, one of which is a diuretic).
Detailed description
This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg baxdrostat versus placebo, administered once a day (QD) orally, on the reduction of ambulatory SBP in participants with rHTN, defined as BP targets not being achieved in an individual despite the use of at least 3 antihypertensive agents of different classes (at maximum tolerated dose in the judgement of the Investigator), one of which is a diuretic.
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD). Unit dose strength: • 2 mg per tablet.
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
* Participant must be ≥ 18 years old, at the time of signing the informed consent. * Mean seated SBP on AOBPM of ≥ 140 mmHg and \< 170 mmHg at Screening. * 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, for at least 4 weeks prior to screening. Beta blockers used to treat other conditions (ie, migraine, HF, coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study. * Have eGFR ≥ 45 mL/min/1.73 m2 at Screening. * Serum potassium (K+) level ≥ 3.5 and \< 5.0 mmol/L at Screening, determined as per central laboratory * Randomization Criteria: mean ambulatory SBP of ≥ 130 mmHg at randomisation.
Exclusion criteria
* Mean seated SBP on AOBPM ≥ 170 mmHg. * Mean seated DBP on AOBPM ≥ 110 mmHg. * Serum sodium level \< 135 mmol/L at Screening, as per central laboratory. * Participant 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 HF class IV. * Persistent atrial fibrillation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Least Square Mean Difference for Change From Baseline in Ambulatory 24-hour Average SBP at Week 12: Treatment Policy Strategy | Baseline to week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Ambulatory Night-time Average SBP (mmHg) at Week 12 LS Means | Baseline to week 12 |
| Change From Baseline in Ambulatory Daytime Average SBP (mmHg) at Week 12 | Baseline to week 12 |
| Change From Baseline in Seated SBP (mmHg) at Week 12 | Baseline to week 12 |
| Achieving Ambulatory 24-hour Average SBP of < 130 mmHg at Week 12 | Baseline to week 12 |
| Change From Baseline in Ambulatory 24-hour Average DBP (mmHg) at Week 12 | Baseline to week 12 |
| Change From Baseline in Ambulatory Night-time Average DBP (mmHg) at Week 12 | Baseline to week 12 |
| Change From Baseline in Ambulatory Daytime Average DBP (mmHg) at Week 12 | Baseline to week 12 |
| Change From Baseline in Seated DBP (mmHg) at Week 12 | Baseline to week 12 |
| Achieving a Nocturnal SBP Dipping of >= 10% at Week 12 | Baseline to week 12 |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Czechia, Germany, Greece, Hungary, Malaysia, Philippines, Poland, Saudi Arabia, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Pre-assignment details
218 patients were randomised: 109 to baxdrostat 2 mg and 109 to placebo; however, one patient randomised to baxdrostat never received study intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Age (years) | 59.7 Age (years) STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 170 Participants |
| Region of Enrollment ARG | 13 Participants |
| Region of Enrollment AUS | 8 Participants |
| Region of Enrollment BEL | 1 Participants |
| Region of Enrollment BGR | 19 Participants |
| Region of Enrollment CAN | 4 Participants |
| Region of Enrollment CZE | 10 Participants |
| Region of Enrollment DEU | 3 Participants |
| Region of Enrollment ESP | 3 Participants |
| Region of Enrollment GBR | 9 Participants |
| Region of Enrollment GRC | 17 Participants |
| Region of Enrollment HUN | 0 Participants |
| Region of Enrollment MYS | 3 Participants |
| Region of Enrollment PHL | 3 Participants |
| Region of Enrollment POL | 13 Participants |
| Region of Enrollment SAU | 3 Participants |
| Region of Enrollment SVK | 1 Participants |
| Region of Enrollment THA | 4 Participants |
| Region of Enrollment TUR | 19 Participants |
| Region of Enrollment TWN | 2 Participants |
| Region of Enrollment USA | 27 Participants |
| Region of Enrollment VNM | 9 Participants |
| Region of Enrollment ZAF | 4 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 109 |
| other Total, other adverse events | 56 / 108 | 39 / 109 |
| serious Total, serious adverse events | 1 / 108 | 1 / 109 |
Outcome results
None listed