Abstract: TH-PO1201
Double-Blind, Randomized Phase 3 Study Comparing Esaxerenone with Placebo in Type 2 Diabetes Patients with Microalbuminuria (ESAX-DN Study)
Session Information
- Late-Breaking Clinical Trials Posters
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- No subcategory defined
Authors
- Kashihara, Naoki, Kawasaki Medical School, Kurashiki City, Japan
- Ito, Sadayoshi, Katta Hospital, Shiroishi, Japan
- Shikata, Kenichi, Center for Innovative Clinical Medicine,Okayama University Hospital, Okayama, Japan
- Nangaku, Masaomi, The University of Tokyo School of Medicine, Tokyo, Japan
- Wada, Takashi, Kanazawa University, Ishikawa, Japan
- Okuda, Yasuyuki, Daiichi Sankyo Co., Ltd., Tokyo, Japan
- Sawanobori, Tomoko, Daiichi Sankyo Co., Ltd., Tokyo, Japan
Background
The progression of kidney disease in type 2 diabetes mellitus (T2DM) is not always adequately controlled by renin-angiotensin system inhibitors. In preclinical studies, Esaxerenone (ESAX), a non-steroidal mineralocorticoid receptor blocker, showed kidney protective effects; it may be effective for diabetic kidney disease. Here, the efficacy and safety of ESAX were evaluated in comparison with placebo in 455 Japanese patients with type 2 diabetes mellitus with microalbuminuria.
Methods
ESAX-DN Study was a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Hypertensive T2DM patients treated with ACEi or ARB with microalbuminuria (UACR ≥45 to <300 mg/g Cr in at least two measurements) and an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 were eligible. Patients were randomized to ESAX (1.25mg to 2.5mg) or placebo groups for 52 weeks with a follow-up of 4 weeks. The primary endpoint was the proportion of patients of UACR remission, defined as a reversal of UACR to normoalbuminuria (<30 mg/g Cr) and a decrease in UACR by ≥30% from baseline at the end of treatment. Secondary endpoints were the change in UACR from baseline, comparison of the transition rate to overt albuminuria at the end of treatment, and safety assessed in terms of adverse events (AEs).
Results
ESAX significantly reduced UACR (-58.3%) compared with placebo (8.4%) (61.6% reduction relative to placebo, P<0.0001), showed a significantly higher UACR remission rate (22.1% vs. 4.0%) and a significantly lower transition rate to overt albuminuria (1.4% vs. 7.5%) compared with placebo (P<0.0001, P=0.0016). Incidence of AEs was similar, ESAX vs. placebo (78.3% vs. 77.3%). The proportion of subjects with serum potassium ≥6.0 mEq/L or with two consecutive readings ≥5.5 mEq/L was higher with ESAX (8.8% vs. 2.2%); patients recovered with ESAX dose adjustment and showed a recovery tendency after the end of the treatment.
Conclusion
This study demonstrated the efficacy of ESAX for UACR remission and a decrease in the transition to overt albuminuria in T2DM patients with microalbuminuria receiving ACEi or ARB. Although the serum potassium increase was higher with ESAX than placebo, all patients tended to recover after treatment and were clinically acceptable.