Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.

CFTR modulators may improve outcomes in patients with COPD, although recent data regarding the magnitude of benefit have been inconclusive, and effects on mucociliary clearance are unknown.

尽管最近关于益处大小的数据尚不明确，且对纤毛运动清除功能的影响尚不清楚，CFTR调节剂可能改善COPD患者的预后。

Objective: We conducted a phase 2, randomized, double-blind, placebo-controlledtrial to determine safety and tolerability and explore the potential mechanism of ivacaftor for the treatment of patients with COPD.

目的：我们进行了一项2期、随机、双盲、安慰剂对照试验，以确定ivacaftor治疗慢性阻塞性肺病（COPD）患者的的安全性和耐受性，并探索其潜在机制。

Methods: We randomized 40 patients with moderate to severe COPD and symptoms of chronic bronchitis to ivacaftor (n = 30) or placebo (n = 10) 150 mg twice daily for 12 weeks.

方法：我们将40名中重度COPD且伴有慢性支气管炎症状的患者随机分为ivacaftor组（n=30）和安慰剂组（n=10），ivacaftor组给予150 mg每日两次，持续12周。

Primary endpoints included evaluation of the safety of ivacaftor and pharmacokinetics.

主要终点包括评估伊瓦卡夫特的安全性和药代动力学。

Secondary endpoints included measures of CFTR activity and clinical outcomes.

次要终点包括测量CFTR活性和临床结果。

Measurements and Main Results: Ivacaftor was safe and tolerable, with similar rates of adverse events between groups.

测量和主要结果：Ivacaftor安全且耐受性良好，两组间不良事件发生率相似。

The most common adverse events were diarrhea in the ivacaftor group and acute COPD exacerbation in the placebo group.

最常见的不良事件是ivacaftor组的腹泻和安慰剂组的急性COPD加重。

Pharmacokinetic analysis showed the mean area under the curve over 12 hours to be 72% of the previously reported value in cystic fibrosis.

药代动力学分析显示，12小时内的平均曲线下面积为囊性纤维化患者先前报告值的72%。

Treatment with ivacaftor did not improve sweat chloride, whole-lung mucociliary clearance, lung function, or respiratory symptoms.

使用伊瓦卡夫特治疗并未改善汗液氯化物、全肺黏液纤毛清除率、肺功能或呼吸症状。

Conclusions: Ivacaftor was safe and well tolerated but did not improve measures of CFTR activity or mucus clearance.

结论：伊瓦卡夫特安全且耐受性良好，但并未改善囊性纤维化转导调节因子（CFTR）活性或粘液清除的指标。

As serum concentrations achieved were lower than observed in cystic fibrosis at the same dose, and modulation of wild-type CFTR differs from G551D, further dose determination studies are needed to better understand the treatment efficacy of CFTR potentiators in COPD.

由于在相同剂量下达到的血清浓度低于囊性纤维化患者，并且野生型CFTR的调节与G551D不同，因此需要进一步的剂量确定研究，以更好地理解CFTR激活剂在慢性阻塞性肺疾病（COPD）中的治疗效果。

Clinical trial registered with www.clinicaltrials.gov (NCT03085485).

该临床试验已在www.clinicaltrials.gov注册（NCT03085485）。