Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis
Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis
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DOI：
10.1183/09031936.02.00025802
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发表时间：
2002-02-01
影响因子：
24.3
通讯作者：
King, M
中科院分区：
文献类型：
--
作者：
App, EM;Baran, D;King, M
本研究的目的是研究一种新型黏液溶解药物Nacystelyn （NAL）治疗囊性纤维化（CF）肺部疾病的耐受性和活性。在研究1中，涉及10名CF患者，主要目的是确定与安慰剂相比，NAL单剂量范围的耐受性和潜在疗效，以便为进一步试验建立最佳剂量。在连续5天的计划治疗中，患者吸入2次（4mg）至8次（16mg）的单剂量NAL，以开放标签的方式给药，或12次活性NAL （24mg）与12次安慰剂，以随机双盲的方式给药。肺功能数据未受影响，临床不良反应仅限于吸入12次安慰剂或活性药物的一些患者的喘息。随后对其痰液的流变学分析显示，痰液粘弹性呈剂量依赖性下降，同时痰中固体含量减少，氯化物和钠浓度增加。在研究2中，涉及12名CIF患者，在24小时内监测单剂量NAL的临床安全性和溶黏液活性。在不同的计划治疗天数，间隔7天，患者以随机双盲顺序吸入单剂量12支活性NAL （24 mg）或12支安慰剂药物，并在吸入前后间隔取痰样本。吸入NAL后粘液硬度降低，在4 h时效果最大；1-、2-和4-h NAL流变学结果与安慰剂有显著差异。未观察到不良反应。在两项研究中，该药的耐受性都很好。痰结果可预测纤毛和咳嗽运输机制改善的清除率。
The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease.In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg) versus 12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations.In study 2, involving 12 CIF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed.The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.