PMID- 32974732
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211230
IS  - 1437-7799 (Electronic)
IS  - 1342-1751 (Print)
IS  - 1342-1751 (Linking)
VI  - 25
IP  - 2
DP  - 2021 Feb
TI  - Apararenone in patients with diabetic nephropathy: results of a randomized, 
      double-blind, placebo-controlled phase 2 dose-response study and open-label 
      extension study.
PG  - 120-130
LID - 10.1007/s10157-020-01963-z [doi]
AB  - BACKGROUND: We investigated the efficacy and safety of apararenone (MT-3995), a 
      non-steroidal compound with mineralocorticoid receptor agonist activity, in 
      patients with stage 2 diabetic nephropathy (DN). METHODS: The study had two 
      parts: a dose-response, parallel-group, randomized, double-blind, 
      placebo-controlled, multicenter, phase 2, 24-week study and an open-label, 
      uncontrolled, 28-week extension study. Primary and secondary endpoints were the 
      24-week percent change from baseline in urine albumin to creatine ratio (UACR) 
      and 24- and 52-week UACR remission rates. Safety parameters were changes from 
      baseline in estimated glomerular filtration rate (eGFR) and serum potassium at 24 
      and 52 weeks, and incidences of adverse events (AEs) and adverse drug reactions 
      (ADRs). RESULTS: In the dose-response period, 73 patients received placebo and 
      73, 74, and 73 received apararenone 2.5 mg, 5 mg, and 10 mg, respectively. As a 
      percentage of baseline, mean UACR decreased to 62.9%, 50.8%, and 46.5% in the 
      2.5 mg, 5 mg, and 10 mg apararenone groups, respectively, at week 24 (placebo: 
      113.7% at week 24; all P < 0.001 vs placebo). UACR remission rates at week 24 
      were 0.0%, 7.8%, 29.0%, and 28.1% in the placebo and apararenone 2.5 mg, 5 mg, 
      and 10 mg groups, respectively. eGFR tended to decrease and serum potassium 
      tended to increase, but these events were not clinically significant. AE 
      incidence increased with dose while ADR incidence did not. CONCLUSION: The 
      UACR-lowering effect of apararenone administered once daily for 24 weeks in 
      patients with stage 2 DN was confirmed, and the 52-week administration was safe 
      and tolerable. CLINICAL TRIAL REGISTRATION: NCT02517320 (dose-response study) and 
      NCT02676401 (extension study).
FAU - Wada, Takashi
AU  - Wada T
AD  - Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, 
      Japan.
FAU - Inagaki, Masaya
AU  - Inagaki M
AD  - Data Science Department, Ikuyaku. Integrated Value Development Division, 
      Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
FAU - Yoshinari, Toru
AU  - Yoshinari T
AD  - Clinical Research and Development II Department, Ikuyaku. Integrated Value 
      Development Division, Mitsubishi Tanabe Pharma Corporation, 17-10, 
      Nihonbashi-Koamicho, Chuo-ku, Tokyo, 103-8405, Japan.
FAU - Terata, Ryuji
AU  - Terata R
AD  - Clinical Research and Development II Department, Ikuyaku. Integrated Value 
      Development Division, Mitsubishi Tanabe Pharma Corporation, 17-10, 
      Nihonbashi-Koamicho, Chuo-ku, Tokyo, 103-8405, Japan.
FAU - Totsuka, Naoko
AU  - Totsuka N
AD  - Clinical Research and Development II Department, Ikuyaku. Integrated Value 
      Development Division, Mitsubishi Tanabe Pharma Corporation, 17-10, 
      Nihonbashi-Koamicho, Chuo-ku, Tokyo, 103-8405, Japan.
FAU - Gotou, Miki
AU  - Gotou M
AD  - Clinical Research and Development II Department, Ikuyaku. Integrated Value 
      Development Division, Mitsubishi Tanabe Pharma Corporation, 17-10, 
      Nihonbashi-Koamicho, Chuo-ku, Tokyo, 103-8405, Japan.
FAU - Hashimoto, Gaia
AU  - Hashimoto G
AD  - Clinical Research and Development II Department, Ikuyaku. Integrated Value 
      Development Division, Mitsubishi Tanabe Pharma Corporation, 17-10, 
      Nihonbashi-Koamicho, Chuo-ku, Tokyo, 103-8405, Japan. 
      hashimoto.gaia@ma.mt-pharma.co.jp.
LA  - eng
SI  - ClinicalTrials.gov/NCT02517320
SI  - ClinicalTrials.gov/NCT02676401
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20200924
PL  - Japan
TA  - Clin Exp Nephrol
JT  - Clinical and experimental nephrology
JID - 9709923
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Oxazines)
RN  - 0 (Sulfonamides)
RN  - 832663U2NB (apararenone)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Albuminuria/urine
MH  - Creatinine/urine
MH  - Diabetic Nephropathies/*drug therapy/physiopathology/urine
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Glomerular Filtration Rate/drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoid Receptor Antagonists/*therapeutic use
MH  - Oxazines/*therapeutic use
MH  - Sulfonamides/*therapeutic use
MH  - Young Adult
PMC - PMC7880964
OTO - NOTNLM
OT  - Apararenone
OT  - Diabetic kidney disease
OT  - Diabetic nephropathy
OT  - Dose-finding study
OT  - Fibrosis
OT  - Mineralocorticoid receptor antagonists
COIS- Takashi Wada has received advisory fees and lecture fees from Mitsubishi Tanabe 
      Pharma Corporation. Masaya Inagaki, Toru Yoshinari, Ryuji Terata, Naoko Totsuka, 
      Miki Gotou and Gaia Hashimoto are employees of Mitsubishi Tanabe Pharma 
      Corporation.
EDAT- 2020/09/26 06:00
MHDA- 2021/11/03 06:00
PMCR- 2020/09/24
CRDT- 2020/09/25 06:06
PHST- 2020/03/26 00:00 [received]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/09/26 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2020/09/25 06:06 [entrez]
PHST- 2020/09/24 00:00 [pmc-release]
AID - 10.1007/s10157-020-01963-z [pii]
AID - 1963 [pii]
AID - 10.1007/s10157-020-01963-z [doi]
PST - ppublish
SO  - Clin Exp Nephrol. 2021 Feb;25(2):120-130. doi: 10.1007/s10157-020-01963-z. Epub 
      2020 Sep 24.