Efficacy and safety of esaxerenone (CS-3150) in Japanese patients with type 2 diabetes and macroalbuminuria: a multicenter, single-arm, open-label phase III study

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Esaxerenone has potential renoprotective effects and reduces the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease and overt nephropathy. We investigated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes (T2D) and macroalbuminuria (UACR ≥ 300 mg/g creatinine).</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a multicenter, single-arm, open-label phase III study in 56 patients with T2D and UACR ≥ 300 mg/g creatinine with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m<jats:sup>2</jats:sup> and treated with a renin–angiotensin system inhibitor. Patients received esaxerenone for 28 weeks at 1.25 mg/day initially with titration to 2.5 mg/day based on serum potassium (K<jats:sup>+</jats:sup>) monitoring. Efficacy was evaluated as the change in UACR from baseline to week 28. Safety endpoints included adverse events (AEs), incidence of serum K<jats:sup>+</jats:sup> increase, and change in eGFR from baseline.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>UACR decreased by 54.6% (95% CI 46.9%, 61.3%) on average from baseline (544.1 mg/g creatinine) to the end of treatment (246.8 mg/g creatinine); 51.8% of patients showed improvement to early nephropathy. AE incidence was 69.6%. Three patients (5.4%) had serum K<jats:sup>+</jats:sup> levels ≥ 6.0 mEq/L or ≥ 5.5 mEq/L on two consecutive occasions. Hyperkalemia in two patients was transient and resolved during the treatment period. One patient discontinued following two consecutive serum K<jats:sup>+</jats:sup> values ≥ 5.5 mEq/L. The maximum change from baseline in eGFR was − 8.3 mL/min/1.73 m<jats:sup>2</jats:sup> at week 24.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Esaxerenone reduced UACR in Japanese patients with T2D and UACR ≥ 300 mg/g creatinine; more than half experienced a transition from UACR ≥ 300 mg/g creatinine to UACR < 300 mg/g creatinine.</jats:p> </jats:sec><jats:sec> <jats:title>Clinical trial registration</jats:title> <jats:p>JapicCTI-173696</jats:p> </jats:sec>