PMID- 34110524
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20220121
IS  - 1437-7799 (Electronic)
IS  - 1342-1751 (Print)
IS  - 1342-1751 (Linking)
VI  - 25
IP  - 10
DP  - 2021 Oct
TI  - 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.
PG  - 1070-1078
LID - 10.1007/s10157-021-02075-y [doi]
AB  - 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 m(2) 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 m(2) 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.
CI  - (c) 2021. The Author(s).
FAU - Ito, Sadayoshi
AU  - Ito S
AD  - Division of Nephrology, Endocrinology and Vascular Medicine, Department of 
      Medicine, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 
      Sendai, Miyagi, 980-8575, Japan. db554@med.tohoku.ac.jp.
AD  - Katta General Hospital, Shiroishi, Japan. db554@med.tohoku.ac.jp.
FAU - Kashihara, Naoki
AU  - Kashihara N
AD  - Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, 
      Japan.
FAU - Shikata, Kenichi
AU  - Shikata K
AD  - Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, 
      Japan.
FAU - Nangaku, Masaomi
AU  - Nangaku M
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Wada, Takashi
AU  - Wada T
AD  - Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, 
      Japan.
FAU - Okuda, Yasuyuki
AU  - Okuda Y
AD  - Data Intelligence Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Sawanobori, Tomoko
AU  - Sawanobori T
AD  - Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210610
PL  - Japan
TA  - Clin Exp Nephrol
JT  - Clinical and experimental nephrology
JID - 9709923
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Pyrroles)
RN  - 0 (Sulfones)
RN  - AYI8EX34EU (Creatinine)
RN  - N62TGJ04A1 (esaxerenone)
SB  - IM
MH  - Aged
MH  - Albuminuria/*drug therapy/etiology/urine
MH  - Creatinine/urine
MH  - Diabetes Mellitus, Type 2/complications
MH  - Diabetic Nephropathies/complications/*drug therapy/urine
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Hyperkalemia/chemically induced
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/adverse effects/*therapeutic use
MH  - Pyrroles/adverse effects/*therapeutic use
MH  - Sulfones/adverse effects/*therapeutic use
PMC - PMC8421271
OTO - NOTNLM
OT  - Esaxerenone
OT  - Macroalbuminuria
OT  - Phase III
OT  - Type 2 diabetes
OT  - Urinary albumin-to-creatinine ratio
COIS- Employment: Yasuyuki Okuda (Daiichi Sankyo Co., Ltd.) and Tomoko Sawanobori 
      (Daiichi Sankyo Co., Ltd); Personal fees: Sadayoshi Ito (Daiichi Sankyo Co., 
      Ltd.), Naoki Kashihara (Daiichi Sankyo Co., Ltd.), Kenichi Shikata (Daiichi 
      Sankyo Co., Ltd.), Masaomi Nangaku (Daiichi Sankyo Co., Ltd.), and Takashi Wada 
      (Daiichi Sankyo Co., Ltd); Grants/research funding received: Sadayoshi Ito 
      (Daiichi Sankyo Co., Ltd.), Naoki Kashihara (Daiichi Sankyo Co., Ltd.), and 
      Masaomi Nangaku (Daiichi Sankyo Co., Ltd).
EDAT- 2021/06/11 06:00
MHDA- 2022/01/22 06:00
PMCR- 2021/06/10
CRDT- 2021/06/10 12:31
PHST- 2021/02/28 00:00 [received]
PHST- 2021/05/10 00:00 [accepted]
PHST- 2021/06/11 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/06/10 12:31 [entrez]
PHST- 2021/06/10 00:00 [pmc-release]
AID - 10.1007/s10157-021-02075-y [pii]
AID - 2075 [pii]
AID - 10.1007/s10157-021-02075-y [doi]
PST - ppublish
SO  - Clin Exp Nephrol. 2021 Oct;25(10):1070-1078. doi: 10.1007/s10157-021-02075-y. 
      Epub 2021 Jun 10.