Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), versus placebo in patients with non-alcoholic fatty liver disease.
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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DOI：
10.1111/apt.16596
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发表时间：
2021-11
影响因子：
7.6
通讯作者：
Loomba, Rohit
中科院分区：
文献类型：
--
作者：
Nakajima, Atsushi;Eguchi, Yuichiro;Yoneda, Masato;Imajo, Kento;Tamaki, Nobuharu;Suganami, Hideki;Nojima, Toshiaki;Tanigawa, Ryohei;Iizuka, Masakazu;Iida, Yuki;Loomba, Rohit
培马替特是一种新型的选择性过氧化物酶体增殖物激活受体α调节剂（SPPARMα）。在小鼠实验中，培马布特改善了非酒精性脂肪性肝炎（NASH）的组织学特征。在血脂异常患者中，它可改善血清丙氨酸转氨酶（ALT）。评价培马布特治疗高风险非酒精性脂肪肝（NAFLD）患者的疗效和安全性。这项双盲、安慰剂对照、随机多中心、2期试验将118例患者（1:1）随机分配至0.2 mg培马布拉特或安慰剂组，每日口服两次，持续72周。主要纳入标准包括肝脏脂肪含量≥10%（磁共振成像-估计质子密度脂肪分数（MRI - PDFF））；肝刚度≥2.5 kPa，磁共振弹性成像（MRE）；ALT水平升高主要终点是MRI - PDFF从基线到第24周的百分比变化。次要终点包括基于MRE的肝硬度、ALT、血清肝纤维化标志物和脂质参数。在主要终点，两组间无显著差异（- 5.3% vs - 4.2%；治疗差异- 1.0%,P = 0.85）。然而，与安慰剂相比，基于MRE的肝硬度在第48周显著降低（治疗差异- 5.7%,P = 0.036），并在第72周保持不变（治疗差异- 6.2%,P = 0.024）， ALT和LDL‐C显著降低。不良事件在治疗组之间具有可比性，治疗耐受性良好。培马布特没有降低肝脏脂肪含量，但显著降低了基于MRE的肝脏硬度。培马替特可能是一种很有前景的治疗NAFLD/NASH的药物，也是与降低肝脏脂肪含量的药物联合治疗的候选药物。ClinicalTrials.gov，号码：NCT03350165。
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). To evaluate the efficacy and safety of Pemafibrate in patients with high‐risk, non‐alcoholic fatty liver disease (NAFLD). 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. There was no significant difference between the groups in the primary endpoint (−5.3% vs −4.2%; treatment difference −1.0%, P = 0.85). However, MRE‐based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference −5.7%, P = 0.036), and was maintained at week 72 (treatment difference −6.2%, P = 0.024), with significant reduction in ALT and LDL‐C. Adverse events were comparable between the treatment groups and therapy was well tolerated. 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.
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影响因子：
6.3
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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Fruchart JC