TY - JOUR
T1 - Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis
T2 - A randomized controlled study
AU - Okanoue, Takeshi
AU - Sakamoto, Michiie
AU - Harada, Kenichi
AU - Inagaki, Masaya
AU - Totsuka, Naoko
AU - Hashimoto, Gaia
AU - Kumada, Hiromitsu
N1 - Funding Information:
T. Okanoue received remuneration from Mitsubishi Tanabe Pharma Corporation during the conduct of the study. M. Sakamoto received research funding from Mitsubishi Tanabe Pharma Corporation during the conduct of the study, and has received research funding from Eisai Co., Ltd., Olympus Corporation, FUJI FILM Corporation, and CYTLIMIC Inc. outside the submitted work. K. Harada received remuneration from Mitsubishi Tanabe Pharma Corporation during the conduct of the study, and has received remuneration from Gilead Sciences Inc., Otsuka Pharmaceutical, and Taisho Toyama Co., Ltd outside the submitted work. M. Inagaki, N. Totsuka, and G. Hashimoto are employees of Mitsubishi Tanabe Pharma Corporation. H. Kumada received remuneration from Mitsubishi Tanabe Pharma Corporation during the conduct of the study, and has received remuneration from AbbVie Inc, Eisai Co., Ltd., Gilead Sciences K.K., Sumitomo Dainippon Pharma Co., Ltd., and MSD K.K. outside the submitted work.
Publisher Copyright:
© 2021 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.
PY - 2021/9
Y1 - 2021/9
N2 - Aim: To evaluate the efficacy, safety, and tolerability of apararenone 10 mg/day in patients with nonalcoholic steatohepatitis (NASH). Methods: In this multicenter, randomized, double-blind, placebo-controlled phase II study, patients received apararenone 10 mg or placebo once daily for 72 weeks. The primary efficacy end-point was percent change in serum alanine aminotransferase (ALT) from baseline to 24 weeks after randomization. Secondary efficacy end-points included changes in liver fibrosis markers. Adverse drug reactions (ADRs) and serum potassium levels were evaluated. Results: Forty-eight patients were randomly assigned to treatment (placebo, 23; apararenone, 25). The percent change in ALT at 24 weeks was −3.0% and −13.7% with placebo and apararenone, respectively (p = 0.308). The apararenone group showed greater reductions from baseline in fibrosis markers (type IV collagen 7S and procollagen-3 N-terminal peptide) and noninvasive tests of fibrosis (enhanced liver fibrosis score and Fibrosis-4 index) at all time points versus placebo. The percentage of patients with improvement of 1 point or more in fibrosis stage/without nonalcoholic fatty liver disease activity score worsening was 41.7% with apararenone and 26.1% with placebo (p = 0.203). Adverse drug reactions were reported in three (13.0%) and three (12.5%) patients in the placebo and apararenone groups, respectively. Serum potassium levels increased in the apararenone group during the study and decreased to near baseline after the end of treatment. Conclusions: In patients with NASH, apararenone 10 mg/day for 72 weeks was effective in decreasing ALT levels, improved multiple potential fibrosis markers, and was safe and well tolerated. Pathological findings showed anti-inflammatory and antifibrotic effects of apararenone.
AB - Aim: To evaluate the efficacy, safety, and tolerability of apararenone 10 mg/day in patients with nonalcoholic steatohepatitis (NASH). Methods: In this multicenter, randomized, double-blind, placebo-controlled phase II study, patients received apararenone 10 mg or placebo once daily for 72 weeks. The primary efficacy end-point was percent change in serum alanine aminotransferase (ALT) from baseline to 24 weeks after randomization. Secondary efficacy end-points included changes in liver fibrosis markers. Adverse drug reactions (ADRs) and serum potassium levels were evaluated. Results: Forty-eight patients were randomly assigned to treatment (placebo, 23; apararenone, 25). The percent change in ALT at 24 weeks was −3.0% and −13.7% with placebo and apararenone, respectively (p = 0.308). The apararenone group showed greater reductions from baseline in fibrosis markers (type IV collagen 7S and procollagen-3 N-terminal peptide) and noninvasive tests of fibrosis (enhanced liver fibrosis score and Fibrosis-4 index) at all time points versus placebo. The percentage of patients with improvement of 1 point or more in fibrosis stage/without nonalcoholic fatty liver disease activity score worsening was 41.7% with apararenone and 26.1% with placebo (p = 0.203). Adverse drug reactions were reported in three (13.0%) and three (12.5%) patients in the placebo and apararenone groups, respectively. Serum potassium levels increased in the apararenone group during the study and decreased to near baseline after the end of treatment. Conclusions: In patients with NASH, apararenone 10 mg/day for 72 weeks was effective in decreasing ALT levels, improved multiple potential fibrosis markers, and was safe and well tolerated. Pathological findings showed anti-inflammatory and antifibrotic effects of apararenone.
KW - alanine aminotransferase
KW - clinical trial
KW - fibrosis
KW - mineralocorticoid receptor antagonist
KW - nonalcoholic steatohepatitis
KW - phase II
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U2 - 10.1111/hepr.13695
DO - 10.1111/hepr.13695
M3 - Article
AN - SCOPUS:85111862821
VL - 51
SP - 943
EP - 956
JO - Hepatology Research
JF - Hepatology Research
SN - 1386-6346
IS - 9
ER -