INTRODUCTION: Patients with primary biliary cholangitis (PBC) without biochemical response to ursodeoxycholic acid (UDCA) are at increased risk of liver-related mortality. Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual PPAR agonistic properties (α/γ). There is a strong mechanistic rationale for studying saroglitazar in PBC because PPARα is a molecular target of fibrates that showed improvements in liver tests in patients with PBC. METHODS: In this 16-week, open-label, phase 3 study, 37 patients were screened across 3 clinical centers to enroll 7 patients. All patients received daily dose of saroglitazar 4 mg for 16 weeks in addition to their ongoing treatment with UDCA. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at week 16 as compared to baseline. RESULTS: Mean age of the study population was 51.1 ± 10.0 years, all patients were female of Mexican descent, and mean body mass index was 25.5± = 4.8 kg/m ~(2). Six (85.7%) patients reported taking ursodiol at baseline and continued throughout the study with a mean daily dosage of 417 mg. Among these, the daily dosage of UDCA 500 mg in 4 and 250 mg in 2 subjects, respectively. The mean baseline ALP level was 230 ± 103 U/L. The primary efficacy endpoint, mean change (reduction) from baseline in ALP concentration at week 16 based on the modified intent-to-treat population was ?94 ± 53 U/L ( P = 0.003), corresponding to a reduction of 48 ± 23%. Treatment with saroglitazar 4 mg resulted in a rapid and sustained decrease of ALP levels at week 4 (?84 ± 47 U/L, P = 0.003). Six patients who completed the study achieved mean ALP reduction of at least 40% at week 4 and all subsequent visits. DISCUSSION: Although the study was terminated because of lack of enrollment, saroglitazar daily for 16 weeks resulted in rapid and sustained improvements in ALP with an acceptable safety profile in patients with PBC.
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机译：简介：对尿嘧啶胆酸（UDCA）没有生物化学反应的原代胆管炎（PBC）的患者处于肝脏相关死亡率的风险增加。 Saroglitazar是一种新型过氧化物酶体增殖物激活的受体（PPAR）激动剂，具有双PPAR激动性质（α/γ）。在PBC中研究Saroglitazar有强大的机制理由，因为PPARα是匹配的匹配的分子靶标，所述纤维剂在PBC患者中显示出肝脏试验的改善。方法：在本期16周，开放标签，第3阶段研究，37例患者筛查3名临床中心，注册7名患者。除了用UDCA的持续治疗外，所有患者均接受每日服用甲簧4毫克的撒罗曲杉杆菌4毫克。与基线相比，初级疗效终点是在第16周的碱性磷酸酶（ALP）水平的降低。结果：本研究人口的平均年龄为51.1±10.0岁，所有患者均为墨西哥血统，平均体重指数为25.5±= 4.8千克/ m〜（2）。六（85.7％）患者报告以基线服用Ursodiol，并在整个研究中持续，平均每日剂量为417毫克。其中，分别在4个受试者中4和250mg的UDCA 500mg的每日剂量。平均基线ALP水平为230±103 U / L.基于修饰的意图群体的第16周，AlP浓度中基线的主要疗效终点，平均变化（减少）是α94±53 U / L（P = 0.003），对应于48±23的减少％。用甲簧治疗4mg在第4周（α84±47 U / L，P = 0.003）产生快速且持续降低ALP水平。完成该研究的六名患者在第4周和所有后续访问中取得了至少40％的平均alp。讨论：虽然由于缺乏招生而终止了研究，但萨洛吉拉达尔每天服用16周，导致ALP的快速和持续改善，PBC患者具有可接受的安全性。
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