Deterding Robin R, Lavange Lisa M, Engels Jean M, Mathews Dave W, Coquillette Sarah J, Brody Alan S, Millard Steve P, Ramsey Bonnie W
The Children's Hospital, 1056 East 19th Avenue, B395, Denver, CO 80218, USA.
Am J Respir Crit Care Med. 2007 Aug 15;176(4):362-9. doi: 10.1164/rccm.200608-1238OC. Epub 2007 Apr 19.
Denufosol tetrasodium is a selective P2Y(2) agonist that enhances mucosal hydration and mucus clearance by activating Cl(-) secretion and inhibiting epithelial Na(+) transport through a non-cystic fibrosis transmembrane conductance regulator mechanism in the lung.
To examine the safety and efficacy of 28 days of treatment with denufosol compared with placebo in patients with mild cystic fibrosis.
The study was a randomized, double-blind, multi-center, 28-day, phase 2 clinical trial of denufosol tetrasodium inhalation solution (20, 40, or 60 mg) versus placebo (normal saline). Patients with screening FEV(1) >or= 75% of predicted normal value and not treated with inhaled antibiotics for the past 30 days were randomized to receive one of three doses of denufosol or placebo administered three times daily.
Eighty-nine patients were randomized and received the study drug, 94% completed the study, and 98% were compliant with dosing. All treatments were generally well tolerated, with no dose-response trends observed with respect to safety parameters. The most common adverse event was cough (52% of placebo patients and 47% of denufosol patients). Five patients discontinued early due to adverse events, two on placebo and three on denufosol. Denufosol patients (pooling active doses) had significantly higher changes from baseline in FEV(1) (P = 0.006), FEF(25%-75%) (P = 0.008), FVC (P = 0.022), and FEV(1)/FVC (P = 0.047) than placebo patients at the end of the study.
Denufosol administered three times daily for 28 days appeared to be safe and well tolerated in this population with mild cystic fibrosis and provided preliminary evidence of potential benefit in lung function.
地努福索四钠是一种选择性P2Y(2)激动剂，通过激活氯离子分泌并抑制上皮钠转运，经非囊性纤维化跨膜传导调节因子机制增强黏膜水合作用和黏液清除。
研究地努福索治疗28天对比安慰剂治疗轻度囊性纤维化患者的安全性和疗效。
本研究是一项随机、双盲、多中心、为期28天的2期临床试验，比较地努福索四钠吸入溶液（20、40或60毫克）与安慰剂（生理盐水）。筛选时FEV(1)≥预测正常值的75%且过去30天未接受吸入性抗生素治疗的患者被随机分配接受三种剂量的地努福索或安慰剂中的一种，每日给药三次。
89名患者被随机分组并接受研究药物治疗，94%完成研究，98%依从给药。所有治疗总体耐受性良好，未观察到与安全参数相关的剂量反应趋势。最常见的不良事件是咳嗽（安慰剂组患者为52%，地努福索组患者为47%）。5名患者因不良事件提前停药，2名服用安慰剂，3名服用地努福索。在研究结束时，地努福索组患者（合并活性剂量）的FEV(1)、FEF(25%-75%)、FVC和FEV(1)/FVC较基线的变化显著高于安慰剂组患者（P = 0.006、P = 0.008、P = 0.022和P = 0.047）。
在轻度囊性纤维化患者群体中，每日三次给药28天的地努福索似乎安全且耐受性良好，并为肺功能潜在获益提供了初步证据。
