Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2).
Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2).
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DOI：
10.1016/j.eclinm.2021.100847
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发表时间：
2021-05
影响因子：
15.1
通讯作者：
Maspero JF
中科院分区：
文献类型：
--
作者：
Castro M;Kerwin E;Miller D;Pedinoff A;Sher L;Cardenas P;Knorr B;Lawrence D;Ossa D;Wang W;Maspero JF
这些研究评估了非匹普兰（一种前列腺素D2（PGD 2）受体（DP 2）的口服拮抗剂）与安慰剂相比，在哮喘不受控制的患者中加入哮喘标准治疗（SoC）治疗的疗效和安全性。ZEAL-1（NCT 03215758）和ZEAL-2（NCT 03226392）是两项重复、III期、多中心、随机、双盲、安慰剂对照、平行组研究，其中非匹普兰150 mg每日一次（o.d.）在年龄≥12岁且哮喘未得到控制的患者中，在SoC哮喘治疗基础上加用安慰剂。主要终点：治疗12周后给药前1秒用力呼气容积（FEV 1）较基线的变化。关键次要终点：治疗12周后，日间哮喘症状评分、短效β受体激动剂（SABA）使用和哮喘生活质量问卷（AQLQ+12）评分。ZEAL-1中的662名患者和ZEAL-2中的685名患者完成了治疗期。在ZEAL-1中，非维匹纶组给药前FEV 1较基线的最小二乘（LS）平均变化为112 mL，安慰剂组为71 mL（差异[CI]：41 mL; 95% CI：−6，88;校正p值0.088）。在ZEAL-2中，非匹普兰组和安慰剂组给药前FEV 1的LS均值变化分别为126 mL和157 mL（AUC：−31 mL; 95% CI：−80，18;校正p值0.214）。对于这两项研究，治疗组之间的关键次要目的无统计学显著差异。ZEAL研究未显示肺功能或其他临床结局的显著改善。这些结果表明，非匹普兰对DP 2受体的抑制作用在所研究的患者群体中无效。
These studies assessed the efficacy and safety of fevipiprant, an oral antagonist of the prostaglandin D2 (PGD2) receptor (DP2), compared with placebo when added to standard-of-care (SoC) asthma therapy in patients with uncontrolled asthma. ZEAL-1 (NCT03215758) and ZEAL-2 (NCT03226392) are two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies in which fevipiprant 150 mg once daily (o.d.) or placebo was added to SoC asthma therapy in patients aged ≥12 years with uncontrolled asthma. Primary endpoint: change from baseline in pre-dose forced expiratory volume in 1 s (FEV1) after 12 weeks’ treatment. Key secondary endpoints: daytime asthma symptom score, short-acting β-agonist (SABA) use and Asthma Quality-of-Life Questionnaire (AQLQ+12) score after 12-weeks treatment. 662 patients in ZEAL-1 and 685 patients in ZEAL-2 completed the treatment period. In ZEAL-1, the least squares (LS) mean change from baseline in pre-dose FEV1 was 112 mL in fevipiprant vs 71 mL in placebo group (difference [∆]:41 mL; 95% CI: −6, 88; adjusted p-value 0·088). In ZEAL-2, the LS mean change in pre-dose FEV1 was 126 mL and 157 mL in the fevipiprant and placebo groups, respectively (∆:−31 mL; 95% CI: −80, 18; adjusted p-value 0·214). For both studies, there were no statistically significant differences in the key secondary objectives between the treatment groups. The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP2 receptor inhibition with fevipiprant is not effective in the studied patient population.
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影响因子：
3.1
作者：
通讯作者：
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影响因子：
2
作者：
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通讯作者：
Posch, Martin
影响因子：
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作者：
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影响因子：
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影响因子：
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