Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease

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  • Atsushi Nakajima
    Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama Japan
  • Yuichiro Eguchi
    Loco Medical General Institute Saga Japan
  • Masato Yoneda
    Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama Japan
  • Kento Imajo
    Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama Japan
  • Nobuharu Tamaki
    Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
  • Hideki Suganami
    Clinical Data Science Department Kowa Company Ltd Tokyo Japan
  • Toshiaki Nojima
    Clinical Data Science Department Kowa Company Ltd Tokyo Japan
  • Ryohei Tanigawa
    Clinical Development Department Kowa Company Ltd Tokyo Japan
  • Masakazu Iizuka
    Clinical Development Department Kowa Company Ltd Tokyo Japan
  • Yuki Iida
    Clinical Development Department Kowa Company Ltd Tokyo Japan
  • Rohit Loomba
    NAFLD Research Center Division of Gastroenterology Department of Medicine University of California San Diego La Jolla California USA

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<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Pemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non‐alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To evaluate the efficacy and safety of Pemafibrate in patients with high‐risk, non‐alcoholic fatty liver disease (NAFLD).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging‐estimated proton density fat fraction (MRI‐PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI‐PDFF from baseline to week 24. The secondary endpoints included MRE‐based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>There was no significant difference between the groups in the primary endpoint (−5.3% vs −4.2%; treatment difference −1.0%, <jats:italic>P</jats:italic> = 0.85). However, MRE‐based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference −5.7%, <jats:italic>P</jats:italic> = 0.036), and was maintained at week 72 (treatment difference −6.2%, <jats:italic>P</jats:italic> = 0.024), with significant reduction in ALT and LDL‐C. Adverse events were comparable between the treatment groups and therapy was well tolerated.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Pemafibrate did not decrease liver fat content but had significant reduction in MRE‐based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.</jats:p></jats:sec>

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