Paediatric Department, University Hospital Motol, V Uvalu 84, 150 06, Praha, Czech Republic.
Global Clinical Development, Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43122, Parma, Italy.
Eur J Pediatr. 2021 May;180(5):1467-1475. doi: 10.1007/s00431-020-03888-x. Epub 2021 Jan 6.
A new pediatric fixed combination of beclometasone dipropionate (BDP) 50 μg and formoterol fumarate (FF) 6 μg via pressurized metered-dose inhaler (pMDI) (CHF1535, Chiesi, Italy) was investigated. In a double-blind, randomized, placebo-controlled, cross-over study, a single CHF1535 administration using AeroChamber Plus™ spacer device (2 actuations, total dose BDP 100 μg/FF 12 μg) was compared to the same pMDI free combination in 56 asthmatic children aged ≥ 5 and < 12 years. Primary efficacy variable was forced expiratory volume during the first second (FEV) area under the curve corrected by time over 12 h following morning dose (AUC). Further CHF1535 doses (50 μg/6 μg, 100 μg/12 μg, and 200 μg/24 μg) were also explored. Adverse events, electrocardiogram, and vital signs were monitored for safety. CHF1535 was non-inferior to free combination [adjusted mean difference (95% CI) 0.004 L (- 0.050, 0.041] with lower confidence limit greater than the limit set at 0.1 L. FEV AUC of each CHF1535 dose vs placebo were 0.037 L (p = 0.160), 0.119 L (p < 0.001), and 0.094 (p < 0.001) for 50/6, 100/12, and 200/24, respectively. No safety signals were found.Conclusion: CHF1535 was as effective as free combination BDP/FF, with a trend towards a dose-related response. All treatments were safe.Trial registration: ClinicalTrials.gov ID: NCT01584492 What is Known: •Inhaled pressurized metered-dose solutions (pMDI) are the preferred treatment for pediatric asthma. •Combination therapy of inhaled corticosteroids and long-acting β- agonists is a well-established approach to control airway inflammation and airway obstruction also in pediatric patients. What is New: •A novel pediatric pMDI fixed combination of beclomethasone dipropionate 50 μg and formoterol fumarate 6 μg (CHF 1535) was non-inferior to the free combination at the same dose in pulmonary function over the 12-h post-dose period in asthmatic children, with trend towards a dose-related response.
一种新的儿科布地奈德二丙酸酯（BDP）50μg 和富马酸福莫特罗（FF）6μg 的固定组合药物，通过压力定量气雾剂吸入器（pMDI）（CHF1535，Chiesi，意大利）进行研究。在一项双盲、随机、安慰剂对照、交叉研究中，使用 Aer oChamber Plus™ 间隔器设备（2 次喷雾，总剂量 BDP100μg/FF12μg）单次给予 CHF1535 与相同的 pMDI 自由联合在 56 名年龄≥5 岁且<12 岁的哮喘儿童中进行比较。主要疗效变量是校正后的第 1 秒用力呼气量（FEV）时间曲线下面积（AUC），时间为早晨剂量后 12 小时。还探索了进一步的 CHF1535 剂量（50μg/6μg、100μg/12μg 和 200μg/24μg）。监测不良事件、心电图和生命体征以确保安全性。CHF1535 与自由联合相比非劣效[调整后的平均差异（95%CI）0.004L（-0.050，0.041），置信下限大于设定在 0.1L]。每个 CHF1535 剂量与安慰剂相比的 FEV AUC 分别为 0.037L（p=0.160）、0.119L（p<0.001）和 0.094L（p<0.001），用于 50/6、100/12 和 200/24。未发现安全性信号。结论：CHF1535 与自由联合 BDP/FF 一样有效，且存在剂量相关反应的趋势。所有治疗均安全。试验注册：ClinicalTrials.gov ID：NCT01584492 已知： •吸入式压力定量气雾剂（pMDI）是治疗小儿哮喘的首选治疗方法。 •吸入皮质激素和长效β-激动剂的联合治疗是控制气道炎症和气道阻塞的一种成熟方法，在儿科患者中也是如此。 新发现： •新型儿科 pMDI 固定组合布地奈德二丙酸酯 50μg 和富马酸福莫特罗 6μg（CHF1535）在哮喘儿童中，在给药后 12 小时内，与自由联合的相同剂量相比，肺功能非劣效，且存在剂量相关反应的趋势。
