Aclidinium Has Similar Bronchodilatory Effects to Tiotropium: Presented at ERS

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Title: Aclidinium Has Similar Bronchodilatory Effects to Tiotropium: Presented at ERS
URL: http://www.pslgroup.com/dg/22E53E.htm
Doctor's Guide
October 7, 2008

By Chris Berrie

BERLIN -- October 7, 2008 -- Dry-powder inhalation of the anticholinergic aclidinium bromide 200 mcg is well tolerated in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and provides 24-hour bronchodilation that is sustained over 4 weeks and is similar to the anticholinergic tiotropium, according to results of a randomised, double-blind, dose-finding, phase 2 study.

Ronald Dahl, MD, PhD, Respiratory Medicine, Aarhus University Hospital, Aarhus, Denmark, presented the findings here on October 6 at the European Respiratory Society (ERS) 18th Annual Congress.

Aclidinium bromide, a novel, long-acting, anticholinergic agent, is under investigation for maintenance treatment of patients with COPD. Dr. Dahl and colleagues conducted their study to assess the efficacy, tolerability, and safety of aclidinium bromide administered using a multidose dry-powder inhaler and to find the minimal effective dose and the optimal dose.

Aclidinium bromide was administered in once-daily doses of 25, 50, 100, 200, and 400 mcg. Comparators were placebo and open-label standard dose tiotropium 18 mcg.

Inclusion criteria were moderate/stable severe COPD, age 40 years or older, forced expiratory volume at 1 second (FEV₁) 30% to 65% predicted, FEV₁/forced vital capacity (FVC) 70% or less, FEV₁ variability <20% from screening to randomisation, and smoking history of 10 pack years. The exclusion criteria included significant cardiovascular conditions, clinical diagnosis of asthma, and COPD exacerbations within the previous month.

The primary efficacy measure was the trough FEV₁ on day 29. Secondary efficacy measures included trough FEV₁ and FVC responses, FEV₁ and FVC over 0 to 6 hours after administration, and change from baseline of peak FEV₁ and FVC. Questionnaires determined patient conditions, and safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram (ECG), and adverse events.

After screening, 14-day run-in, and randomisation, the mean baseline characteristics of the 460 patients in the intention-to-treat (ITT) population included the following: age, 61.5 years; percent predicted FEV₁, 47.5; FEV₁/FVC, 53.5%; bronchial reversibility at 30 minutes, 7.8%; cigarette consumption, 44.2 pack years; current smokers, 54.6%.

In the ITT population, 64 patients received placebo, 65 patients received aclidinium bromide 25 mcg, 65 received 50 mcg, 69 received 100 mcg, 66 received 200 mcg, and 67 received 400 mcg; 64 patients received tiotropium 18 mcg. About 95% of patients in each treatment group completed the full treatment course.

For the primary efficacy of trough FEV₁ on day 29, significant increases over placebo (P < .05) were only seen for aclidinium bromide 200 mcg (148 mL) and 400 mcg (128 mL), and for tiotropium 18 mcg (161 mL). Similarly, FVC on day 29 saw significance (P < .05) for aclidinium bromide 200 mcg and tiotropium.

For all doses of aclidinium bromide and for tiotropium, changes from baseline in FEV₁ for the first 6 hours postdose on day 1 were similar to those on day 29. Peak FEV₁ on both days 1 and 29 saw significance over placebo for aclidinium bromide 100, 200, and 400 mcg, and for tiotropium.

Incidence of adverse events was low at all aclidinium bromide doses, with no relationship between aclidinium bromide doses and incidence or severity of adverse events. Similarly, there were no clinically relevant changes in laboratory parameters, vital signs, and ECGs.

Dr. Dahl indicated that aclidinium bromide appears to be safe up to 400 mcg daily in patients with moderate or severe COPD. Although the minimum effective dose of aclidinium bromide was 100 mcg, as Dr. Dahl noted, in addition, the 200-mcg aclidinium dose was seen to have superior effects to the 100-mcg dose, he said.

Funding for this study was provided by Forest Laboratories Inc.

[Presentation title: Once Daily Administration of Aclidinium Bromide, a Novel, Long-Acting Anticholinergic: A Phase 2, Dose-Finding Study. Abstract O2736]

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