Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis
Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis
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DOI：
10.1183/13993003.00663-2018
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发表时间：
2019-03-01
影响因子：
24.3
通讯作者：
Kolb, Martin
中科院分区：
文献类型：
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作者：
Khalil, Nasreen;Manganas, Helene;Kolb, Martin
PBI-4050是一种新型口服活性小分子化合物，在包括肺纤维化在内的多种纤维化模型中显示出抗纤维化活性。我们介绍了我们首次在特发性肺纤维化(IPF)患者中应用PBI-4050的临床研究结果。这项为期12周的开放研究探讨了每天单独口服800 mg PBI-4050以及与奈替达尼或吡非尼酮联合使用对以轻度或中度IPF为主的患者的安全性、有效性和药代动力学。9例患者接受PBI-4050治疗，16例患者接受PBI-4050联合治疗，16例患者接受PBI-4050联合吡非尼酮治疗，单用PBI-4050或联合应用9tedanib或吡非尼酮耐受良好。PBI-4050单独给药组和PBI-4050+九替丹尼布组的药物动力学曲线相似，但在PBI-4050+吡非尼酮组降低，提示药物-药物相互作用。从基线到第12周，单独使用PBI-4050或PBI-4050+九替丹尼布的用力肺活量(FVC)，无论是预测百分比还是毫升，都没有显著变化。相比之下，在统计上显著下降(p
PBI-4050 is a novel orally active small-molecule compound with demonstrated anti-fibrotic activity in several models of fibrosis, including lung fibrosis. We present results from our first clinical study of PBI-4050 in patients with idiopathic pulmonary fibrosis (IPF).This 12-week open-label study explored the safety, efficacy and pharmacokinetics of daily oral doses of 800 mg PBI-4050 alone and in combination with nintedanib or pirfenidone in patients with predominantly mild or moderate IPF. Nine patients received PBI-4050 alone, 16 patients received PBI-4050 with nintedanib and 16 patients received PBI-4050 with pirfenidone.PBI-4050 alone or in combination with nintedanib or pirfenidone was well tolerated. Pharmacokinetic profiles for PBI-4050 were similar in the PBI-4050 alone and PBI-4050+ nintedanib groups but reduced in the PBI-4050+ pirfenidone group, suggesting a drug-drug interaction.There were no significant changes in forced vital capacity (FVC), either in % predicted or mL, from baseline to week 12 for PBI-4050 alone or PBI-4050+ nintedanib. In contrast, a statistically significant reduction (p