Twice-daily treatment with aclidinium, an investigational longacting muscarinic antagonist in phase 3 development, results in sustained bronchodilation and improvement in lung function in patients with chronic obstructive pulmonary disease (COPD), according to the results of 2 randomized, controlled clinical trials presented at Chest 2010.
Aclidinium Improves COPD Outcomes
The first was a placebo-controlled, double-blind, 12-week study of 561 patients with moderate-to-severe, stable COPD who were randomized to aclidinium, 200 μg or 400 μg twice daily, or placebo. Patients could continue using salbutamol and inhaled, oral, or parenteral corticosteroids (up to 10 mg/day or 20 mg every other day) as needed. A total of 467 patients completed the study.
According to the investigators, led by Edward Kerwin, MD, at the Clinical Research Institute in Medford, OR, “Cholinergic tone is the major reversible component of airflow obstruction; thus, therapy with anticholinergics can be effective in the treatment of COPD.”
The change from baseline in trough forced expiratory volume in 1 second (FEV1) at week 12 was 86 mL greater in the patients randomized to aclidinium 200 μg and 124 mL greater in those randomized to aclidinium 400 μg compared with placebo.
The change in peak FEV1 from baseline to week 12 was 146 mL greater in the aclidinium 200-μg group compared with placebo, and 192 mL greater in the aclidinium 400-μg group compared with placebo.
Both doses of aclidinium were associated with significantly better improvement compared with placebo in scores on the St. George’s Respiratory Questionnaire (a standardized, self completed questionnaire for measuring impaired health and perceived well-being in airways disease) and in the transitional dyspnea index.
Both doses of aclidinium were welltolerated. The incidence of treatmentemergent serious adverse events was 2.2% in the placebo group, 4.3% in the aclidinium 200-μg group, and 3.2% in the aclidinium 400-μg group.
Aclidinium Safe and Effective for COPD
In the second randomized, doubleblind study, German investigators compared the safety and efficacy of aclidinium 400 μg twice daily with placebo and with tiotropium 18 μg once daily in 30 patients with moderate- to-severe COPD. Patients were treated for 15 days with their assigned therapy and then crossed over to another therapy, until they completed 15 days in each of the 3 arms, with a washout period of 9 to 15 days between treatments.
The normalized FEV1 area under the curve for 12 hours immediately after morning dose administration on day 15 was increased significantly with aclidinium or tiotropium compared with placebo. The researchers reported that optimal bronchodilation was achieved as early as the first day of treatment.
The bronchodilatory effect of aclidinium and tiotropium versus placebo was sustained over 24 hours on day 15.
The average use of rescue medications declined significantly from baseline in the aclidinium (–1.48 puffs) and tiotropium (–0.79 puffs) groups compared with those receiving a placebo (–0.53 puffs).
In addition, aclidinium—but not tiotropium—significantly reduced the scores for breathlessness, cough, and nighttime symptoms compared with placebo.