Ferrari Antonio, Compagnoni Anna, Nandeuil Anne, Maison-Blanche Pierre
*Global Clinical Development Department, Chiesi Farmaceutici, Parma, Italy; and †Cardiology Unit, Hopital Bichat University Hospital, Paris, France.
J Cardiovasc Pharmacol. 2016 Jul;68(1):41-8. doi: 10.1097/FJC.0000000000000384.
Chronic obstructive pulmonary disease (COPD) is a multicomponent condition characterized by airway inflammation and associated to comorbidities, including cardiovascular diseases. Among anti-inflammatory agents in development for COPD, the phosphodiesterase inhibitors administrated by inhalation have the potential for increased efficacy and reduced systemic side effects. CHF6001 is an inhaled PDE4 inhibitor with proven anti-inflammatory properties in animal models. This randomized, double-blind, placebo-controlled study was aimed to demonstrate its cardiovascular safety and tolerability in healthy male volunteers with normal electrocardiogram and cardiac parameters. Single and multiple ascending doses (7 days of administration) of CHF6001 were administered. Three electrocardiograms were recorded at several pharmacokinetic time points and at each time points, postdose heart rate, QRS and PR intervals, and presence of arrhythmia were evaluated. In single ascending dose, QTcF intervals did not increase more than 30 milliseconds from the baseline, all heart rate was between 45 and 100 bpm, and no statistically significant differences were observed in PR and QRS intervals. In multiple ascending dose, cardiac parameters did not differ significantly from baseline. In the pharmacokinetic/pharmacodynamic analysis, no medically or clinically significant changes were found. Further studies are ongoing to demonstrate that CHF6001 is safe and well tolerated in COPD patients as well.
慢性阻塞性肺疾病（COPD）是一种多因素疾病，其特征为气道炎症，并与包括心血管疾病在内的合并症相关。在正在研发用于治疗COPD的抗炎药物中，吸入用磷酸二酯酶抑制剂具有提高疗效和减少全身副作用的潜力。CHF6001是一种吸入用PDE4抑制剂，在动物模型中已证实具有抗炎特性。这项随机、双盲、安慰剂对照研究旨在证明其在心电图和心脏参数正常的健康男性志愿者中的心血管安全性和耐受性。给予CHF6001单次和多次递增剂量（给药7天）。在几个药代动力学时间点记录三份心电图，并在每个时间点评估给药后心率、QRS和PR间期以及心律失常的情况。在单次递增剂量时，QTcF间期较基线增加不超过30毫秒，所有心率均在45至100次/分钟之间，PR和QRS间期未观察到统计学上的显著差异。在多次递增剂量时，心脏参数与基线无显著差异。在药代动力学/药效学分析中，未发现具有医学或临床意义的变化。正在进行进一步研究以证明CHF6001在COPD患者中同样安全且耐受性良好。
