吸入性粉剂Tudorza Pressair获准用于治疗成人COPD

圣路易斯(MD Consult)——2012年7月23日，森林实验室制药公司、Almirall公司及美国食品药品管理局(FDA)宣布，Tudorza Pressair(阿地溴铵吸入性粉剂)获准用作慢性阻塞性肺病(COPD)引起的支气管痉挛的长期维持治疗药。Tudorza为每日2次用药，属于吸入性长效抗胆碱药，其作用机制为通过抑制乙酰胆碱对气管平滑肌毒蕈碱受体的作用，促进支气管扩张。

Tudorza Pressair临床发展计划包括1项探讨剂量范围的试验及3项确证性关键性试验。2项历时12周及1项历时24周的关键性安慰剂对照试验在1,276例患者中对Tudorza 400 μg、每日2次用药的有效性和安全性进行了评估。入选这些试验的患者均在临床上被诊断患有COPD，年龄≥40岁，有至少10包-年的吸烟史，1秒用力呼气量(FEV1)/预测正常值介于30%~80%，FEV1/用力肺活量(FEV1/FVC)<0.7。

这3项关键性试验均显示，Tudorza Pressair在扩张支气管方面较安慰剂有统计学意义的改善，衡量指标为12周时早晨给药前的FEV1谷值相对于基线的变化(主要终点)。12周时给药前FEV1相对于安慰剂的平均改善幅度为0.12 L、0.07 L及0.11 L，而在6个月的试验中24周时的改善幅度为0.13 L。在给予首剂Tudorza后的评估结果显示，肺功能(FEV1)平均峰改善幅度与各项研究中第12周的观察结果相近。

在其中2项试验中，接受Tudorza Pressair治疗的患者每日抢救药物沙丁胺醇的用量也少于安慰剂对照组患者。

在这些试验中，Tudorza Pressair组最常见的不良反应为头痛、鼻咽炎及咳嗽。3项长期安全性研究中治疗组患者报告的不良事件相近，与安慰剂对照试验相比，未出现新的安全性问题，这3项研究共包括891例接受Tudorza Pressair 400 μg、每日2次治疗的患者。

使用Tudorza Pressair治疗可能会引起严重的不良反应，其中包括矛盾性支气管痉挛，新发窄角型青光眼或加重，新发尿潴留或加重。Tudorza Pressair不宜用作急性支气管痉挛的抢救治疗，并且不宜用于18岁以下的患者。

爱思唯尔  版权所有

ST LOUIS (MD Consult) - On July 23, 2012, Forest Laboratories, Almirall, and the US Food and Drug Administration (FDA) announced the approval of Tudorza Pressair (aclidinium bromide inhalation powder) for long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Tudorza is a twice-daily inhaled long-acting anticholinergic. Use of the product promotes bronchodilation by inhibiting acetylcholine's effect on muscarinic receptors in the airway smooth muscle.

The Tudorza Pressair clinical development program included a dose-ranging trial and 3 confirmatory pivotal trials. The 2 12-week and 1 24-week pivotal placebo-controlled trials evaluated the efficacy and safety of Tudorza 400 μg twice daily in 1276 patients. Patients enrolled in these trials had a clinical diagnosis of COPD, were at least 40 years old, had a smoking history of at least 10 pack-years, a forced expiratory volume in one second (FEV1) of at least 30% and less than 80% of predicted normal value, and a ratio of FEV1 over forced vital capacity (FEV1/FVC) of < 0.7.

In all 3 pivotal trials, Tudorza Pressair demonstrated statistically significant improvements in bronchodilation, as measured by change from baseline in morning predose trough FEV1 at 12 weeks (the primary end point) compared with placebo. The mean 12-week predose FEV1 improvements versus placebo were 0.12 L, 0.07 L, and 0.11 L in the 3 trials, with a 24-week improvement of 0.13 L in the 6-month trial. Mean peak improvements in lung function (FEV1) assessed after the first dose of Tudorza were similar to those observed at week 12 in each study.

In two of the these trials, patients treated with Tudorza Pressair also used less daily rescue albuterol compared with placebo-treated patients.

The most common adverse reactions that occurred in the Tudorza Pressair group in these trials were headache, nasopharyngitis, and cough. Three long-term safety studies, that included 891 patients treated with Tudorza Pressair 400 μg twice daily for 40 to 52 weeks reported similar adverse events, with no new safety findings compared with the placebo-controlled trials.

The use of Tudorza Pressair may cause serious adverse effects, including paradoxical bronchospasm, new or worsened narrow-angle glaucoma, or new or worsened urinary retention. Tudorza Pressair should not be used as a rescue therapy to treat acute bronchospasm and is not recommended for use in persons younger than 18 years.