A Phase III Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin on CKD Progression in Participants With CKD and High Blood Pressure (BaxDuo-Arctic).

NCT06268873Sponsor: AstraZeneca

About This Study

This Phase III, randomized, double-blind trial evaluates the efficacy and safety of baxdrostat, a selective aldosterone synthase inhibitor, in combination with dapagliflozin for patients with CKD and hypertension. The study population includes adults with CKD and high blood pressure who are either SGLT2i-naive or currently receiving SGLT2i therapy. Participants receive a 4-week dapagliflozin run-in period if treatment-naive, followed by a 24-month double-blind phase comparing baxdrostat/dapagliflozin to dapagliflozin plus placebo. The primary efficacy endpoint assesses CKD progression via changes in GFR following a 6-week open-label dapagliflozin washout period. Secondary outcomes focus on the long-term safety and tolerability of the combination regimen in this high-risk population.

Who Can Participate?

✓ Inclusion Criteria

•Participants of any sex and gender must be ≥ 18 years old, or older, at the time of signing the informed consent.
•Participants with CKD and eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening
•Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening
•Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit
•Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit
•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

•Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening.
•Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.
•Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory.
•Diabetes mellitus:
•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.
•Uncontrolled T2DM at screening: HbA1C > 10.5% (> 91 mmol/mol).
•New York Heart Association functional HF class IV at screening.
•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.
•Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
•Any acute kidney injury within 3 months prior to the Screening Visit
•History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
•History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI.
•Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1.
•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.