The purpose of this study is to measure the efficacy and safety of baxdrostat/dapagliflozin in participants ≥ 18 years of age with CKD and HTN.

This study consists of a screening, a 4-week dapagliflozin run-in period for participants untreated with SGLT2i at baseline; a 24-month double-blind period in which participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin; and approximately 12-week open-label period in which all participants will discontinue baxdrostat/placebo and receive dapagliflozin alone. Site visits will take place at 2-, 4-, 8-, and 16- weeks following randomisation. Thereafter visits will occur approximately every 4 months, until the 24-month visit at which time baxdrostat/placebo will be discontinued. Participants will continue open-label dapagliflozin for another 12-weeks (approximately), where reassessment of eGFR will occur for the primary efficacy endpoint.

In the event of premature discontinuation of blinded study intervention, participants will continue in the study and receive open-label dapagliflozin monotherapy, unless the participant meets dapagliflozin specific discontinuation criteria, in which case all study interventions will be discontinued.

Inclusion Criteria:

1. Participants of any sex and gender must be ≥ 18 years old, or older, at the time of signing the informed consent.

2. Participants with CKD and eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening

3. Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening

4. Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit

5. Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit

6. Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR:

   • for participants with screening eGFR ≥ 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.8 mmol/L at the Screening Visit
   • for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.5 mmol/L at the Screening Visit

Exclusion Criteria:

1. Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening.

2. Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.

3. Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory.

4. Diabetes mellitus:

   (a) T1DM at Screening Visit: (i) For US only: patients with T1DM treated with SGLT2i for at least 4 months, without DKA during that period, and who have experience with ketone monitoring are eligible for inclusion.

   (ii) For Japan only: patients with T1DM treated with dapagliflozin 10 mg for at least 4 months, without DKA during the period of dapagliflozin treatment are eligible for inclusion.

   (b) Uncontrolled T2DM at screening: HbA1C > 10.5% (> 91 mmol/mol).

5. New York Heart Association functional HF class IV at screening.

6. Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation.

7. Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.

8. Any acute kidney injury within 3 months prior to the Screening Visit

9. History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).

10. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI.

11. Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1.

12. Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to 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.

Placebo controlled