WCN26-3911 Novel Renal-cardiac Disease Model: Podocyte-specific MafB Conditional Knockout Mice

Introduction: BaxHTN (NCT06034743) is an international, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of the aldosterone synthase inhibitor baxdrostat in patients with uncontrolled hypertension (uHTN) or resistant hypertension (rHTN).Methods: Participants had a mean seated office systolic blood pressure (seated-SBP) between $140 and <170 mmHg despite treatment with two (uHTN) or $3 (rHTN) antihypertensive treatments (AHT), including a diuretic.Participants with seated-SBP $135 mmHg at the end of a 2-week placebo run-in period were randomised to baxdrostat 2 mg, baxdrostat 1 mg or placebo once daily (QD) for a 12-week doubleblind period.This was followed by a 12-week open-label period of baxdrostat 2 mg QD or standard-of-care, which was followed by an 8week double-blind randomised withdrawal period of baxdrostat 2 mg QD or placebo.There was then a final 20-week open-label period of baxdrostat 2 mg QD.The primary endpoint was change from baseline in seated-SBP at week 12. Results: In total, 796 participants were randomised.794 received at least one dose of study drug: placebo (n=264), baxdrostat 1 mg (n=264) or baxdrostat 2 mg (n=266).At week 12, the placebo-corrected least-squares mean change from baseline in seated-SBP was -8.7 mmHg (95% confidence interval, -11.5 to -5.8; P<0.0001) for baxdrostat 1 mg and -9.8 mmHg (-12.6 to -7.0; P<0.0001) for baxdrostat 2 mg.Treatment was well tolerated with no unanticipated adverse events. Conclusion:The addition of baxdrostat to background AHT led to a reduction in seated-SBP at week 12 compared with placebo in patients with uHTN or rHTN.