Baxdrostat/Dapagliflozin vs. Placebo/Dapagliflozin in Adults with CKD with Hypertension: BaxDuo-Arctic Phase 3 Study Design and Baseline Characteristics

Background Baxdrostat is a selective aldosterone synthase inhibitor that is being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin for the treatment of chronic kidney disease (CKD) with hypertension. We report the design and baseline characteristics of the phase 3, randomized, double-blind BaxDuo-Arctic study (NCT06268873). Methods Eligible adults have seated systolic blood pressure (sSBP) ≥130 mmHg, estimated glomerular filtration rate (eGFR) ≥30 to <90 mL/min/1.73 m², and urine albumin creatinine ratio (UACR) >200 to <5000 mg/g at screening, despite angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment at maximally tolerated dose for ≥4 weeks. Patients with no prior use or <4 weeks of SGLT2i treatment will complete a run-in with dapagliflozin 10 mg once daily (QD) for 4–6 weeks. Patients are randomized 1:1 to receive baxdrostat 1 mg/dapagliflozin 10 mg or placebo/dapagliflozin 10 mg QD for a 104-week double-blind period, followed by a 12-week open-label period with dapagliflozin 10 mg QD. Baxdrostat dose can be uptitrated to 2 mg at week 8 if blood potassium is ≤4.8 mmol/L between week 2 and 8. The primary endpoint is change in eGFR from baseline to the end of the 12-week open-label dapagliflozin period. Adverse events of special interest include hyperkalemia, hyponatremia, and hypotension events that require medical intervention. Results Between March 2024 and November 2025, 2554 patients in 38 countries were randomized. Among 2534 randomized patients with available data at time of submission, 71% were male, 58% had type 2 diabetes, 66% used an SGLT2i at screening, and 71% were on ≥2 antihypertensive medications. Common causes of CKD in patients included diabetic kidney disease (36%), chronic glomerulonephritis (20%), and ischemic/hypertensive nephropathy (18%). Median UACR was 868.0 mg/g. Mean (standard deviation) eGFR and sSBP were 57.3 (15.7) mL/min/1.73 m² and 140.8 (13.9) mmHg, respectively. Conclusion BaxDuo-Arctic will assess the efficacy and safety of baxdrostat/dapagliflozin versus placebo/dapagliflozin on CKD progression in patients with CKD with hypertension.