The purpose of this study is to measure the efficacy and safety of baxdrostat in participants with uHTN or rHTN. The main objective is to compare the difference in SBP change from baseline at Week 12 of treatment between participants receiving 2 mg baxdrostat or 1 mg baxdrostat tablets and participants receiving placebo tablets.

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 QD orally, on the reduction of SBP in approximately 300 participants aged ≥ 18 years with HTN (≥ 140 mmHg at Screening; ≥ 135 mmHg at randomisation) despite a stable regimen of 2 antihypertensive agents at baseline, one of which is a diuretic (uHTN); or ≥ 3 antihypertensive agents at baseline, one of which is a diuretic (rHTN).

Inclusion Criteria:

• Male or female participants must be ≥ 18 years old.

• Mean seated SBP on automated office blood pressure measurement (AOBPM) ≥ 140 mmHg at Screening.

• Fulfil at least 1 of the following 2 criteria:

  1. uHTN subpopulation: have a stable regimen (≥ 4 weeks) 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 (≥ 4 weeks) 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.• Mean seated SBP on AOBPM ≥ 135 mmHg at Baseline.

Exclusion Criteria:

• Mean seated SBP on AOBPM ≥ 170 mmHg.
• Mean seated DBP on AOBPM ≥ 105 mmHg.
• Serum sodium level (Na+) < 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.
• NYHA functional heart failure class IV at Screening.

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.