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).

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request 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.

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.

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.