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

Abstract

Background: 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).

Methods: 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 m² 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⁺) monitoring. Efficacy was evaluated as the change in UACR from baseline to week 28. Safety endpoints included adverse events (AEs), incidence of serum K⁺ increase, and change in eGFR from baseline.

Results: 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⁺ 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⁺ values ≥ 5.5 mEq/L. The maximum change from baseline in eGFR was - 8.3 mL/min/1.73 m² at week 24.

Conclusions: 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.

Clinical trial registration: JapicCTI-173696.

Keywords: Esaxerenone; Macroalbuminuria; Phase III; Type 2 diabetes; Urinary albumin-to-creatinine ratio.

Fig. 1

Time course of urinary albumin-to-creatinine ratio (UACR) values (a) and geometric mean percent change from baseline in UACR (b). End-of-treatment (EOT) values were calculated by taking the average of measurements at the last two visits during the treatment period. Data are shown as geometric mean ± 95% confidence intervals

Fig. 2

Time course of sitting blood pressure (BP) (a) and change in sitting BP from baseline (b). Data are mean ± standard deviation. EOT end of treatment

Fig. 3

Time course of serum potassium (K⁺) (a) and mean change from baseline in serum K⁺ (b). Data are mean ± standard deviation

Fig. 4

Time course of estimated glomerular filtration rate (eGFR) values (a) and mean change from baseline in eGFR (b). Data are mean ± standard deviation. EOT end of treatment