PBI-4050在特发性肺纤维化患者中的二期临床试验,European Respiratory Journal

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PBI-4050在特发性肺纤维化患者中的二期临床试验
European Respiratory Journal ( IF 16.6 ) Pub Date : 2018-12-21 , DOI: 10.1183/13993003.00663-2018
Nasreen Khalil ₁ , Helene Manganas ₂ , Christopher J Ryerson ₃ , Shane Shapera ₄ , Andre M Cantin ₅ , Paul Hernandez ₆ , Eric E Turcotte ₇ , Joseph M Parker ₈ , John E Moran ₈ , Gary R Albert ₈ , Renata Sawtell ₈ , Aline Hagerimana ₈ , Pierre Laurin ₈ , Lyne Gagnon ₈ , Frank Cesari ₈ , Martin Kolb ₉

Affiliation

PBI-4050 是一种新型口服活性小分子化合物，在多种纤维化模型（包括肺纤维化）中显示出抗纤维化活性。我们展示了 PBI-4050 在特发性肺纤维化 (IPF) 患者中的首次临床研究结果。这项为期 12 周的开放标签研究探讨了每日口服 800 mg PBI-4050 单独和与尼达尼布或吡非尼酮联合治疗轻或中度 IPF 患者的安全性、有效性和药代动力学。9 名患者单独接受 PBI-4050，16 名患者接受 PBI-4050 和尼达尼布，16 名患者接受 PBI-4050 和吡非尼酮。PBI-4050 单独使用或与尼达尼布或吡非尼酮联合使用的耐受性良好。PBI-4050 的药代动力学特征在单独的 PBI-4050 和 PBI-4050+尼达尼布组中相似，但在 PBI-4050+吡非尼酮组中降低，表明存在药物相互作用。从基线到第 12 周，单独使用 PBI-4050 或 PBI-4050 + nintedanib 的用力肺活量 (FVC)，无论是预测百分比还是 mL，都没有显着变化。相比之下，12 周后 PBI-4050+吡非尼酮的 FVC % pred 出现统计学显着降低（p<0.024）。在 IPF 患者中，单独使用 PBI-4050 或与尼达尼布或吡非尼酮联合使用没有安全问题。FVC 在基线和第 12 周之间的稳定性对于 PBI-4050 单独和与尼达尼布联合使用看起来令人鼓舞。

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Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis

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<0.024) in FVC % pred was seen for PBI-4050+pirfenidone after 12 weeks. There were no safety concerns with PBI-4050 alone or in combination with nintedanib or pirfenidone in IPF patients. The stability of FVC between baseline and week 12 looked encouraging for PBI-4050 alone and in combination with nintedanib. PBI-4050 alone and in combination with nintedanib demonstrated no safety concerns and showed encouraging results for lung function in IPF patients http://ow.ly/olQD30myD0E

更新日期：2018-12-21

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