A randomised, placebo- and active-controlled dose-finding study of aclidinium bromide administered twice a day in COPD patients

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• 作者：D. Singh^a ; ^{dsingh@meu.org.uk} ; H. Magnussen^b ; ^{magnussen@pulmoresearch.de} ; A. Kirsten^b ; ^{A.Kirsten@pulmoresearch.de} ; S. Mindt^c ; ^{susannemindt@kabelmail.de} ; C. Caracta^d ; ^{Cynthia.Caracta@frx.com} ; B. Seoane^e ; ^{beatriz.seoane@almirall.com} ; D. Jarreta^e ; ^{diana.jarreta@almirall.com} ; E. Garcia Gil^e ; ^{esther.garciagil@almirall.com}
• 关键词：Aclidinium ; Bronchodilation ; COPD ; Phase II ; Twice-daily
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2012
• 期刊代码：56_10945539
• 类别：pha
• 出版时间：June, 2012
• 卷：25
• 期：3
• 页码：248-253
• 文件大小：394 K

摘要

This Phase IIb, double-blind, double-dummy, placebo- and active-comparator-controlled crossover study ( identifier: NCT01120093) assessed efficacy and safety of three doses of aclidinium bromide in patients with moderate to severe chronic obstructive pulmonary disease. Patients were randomised to one of five treatment sequences each consisting of twice-daily (BID) aclidinium 100聽渭g, 200聽渭g, 400聽渭g (via Genuair^庐*), formoterol 12聽渭g (via Aerolizer^庐) and matched placebo for 7 days, with a 5- to 9-day washout period. Primary endpoint was mean change from baseline in forced expiratory volume in 1聽s (FEV₁) normalised area under the curve (AUC)_0-12 on Day 7. Secondary endpoints were: change from baseline in FEV₁ normalised AUC_12-24, FEV₁ normalised AUC_0鈭?4 and morning pre-dose FEV₁ on Day 7. Adverse events were monitored throughout the study. Of 79 randomised patients, 68 (86.1%) completed the study. After 7 days of treatment, aclidinium and formoterol produced statistically significantly greater changes from baseline in FEV₁ normalised AUC_0鈭?2 vs placebo (p聽<聽0.0001). FEV₁ normalised AUC_12鈭?4, FEV₁ normalised AUC_0-24, and morning pre-dose FEV₁ were also statistically significantly greater with all aclidinium doses vs placebo (p聽<聽0.0001). Improvements in primary and secondary endpoints were statistically significantly greater with aclidinium 400聽渭g vs 100聽渭g. The safety profile of aclidinium was comparable to placebo. These results demonstrated that twice-daily aclidinium produced dose-dependent clinically meaningful improvements in FEV₁ compared with placebo. This study also confirmed the use of an aclidinium BID dosing regimen and established aclidinium 200聽渭g and 400聽渭g as suitable doses for further investigation in Phase III trials.