Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis: A randomized controlled study.

Abstract

To evaluate the efficacy, safety, and tolerability of apararenone 10mg/day in patients with nonalcoholic steatohepatitis (NASH). In this multicenter, randomized, double-blind, placebo-controlled phase II study, patients received apararenone 10mg or placebo once daily for 72weeks. The primary efficacy end-point was percent change in serum alanine aminotransferase (ALT) from baseline to 24weeks after randomization. Secondary efficacy end-points included changes in liver fibrosis markers. Adverse drug reactions (ADRs) and serum potassium levels were evaluated. Forty-eight patients were randomly assigned to treatment (placebo, 23; apararenone, 25). The percent change in ALT at 24weeks 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. In patients with NASH, apararenone 10mg/day for 72weeks 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.