Aclidinium bromide is a competitive, selective muscarinic receptor antagonist, with a longer residence time at M3 receptors than M2 receptors. M3 receptors mediate contraction of smooth muscle in the airways; thus, the activity of inhaled aclidinium bromide at these receptors induces bronchodilation. Once absorbed, aclidinium bromide is rapidly broken down in the plasma, resulting in minimal systemic anticholinergic side-effects.1
The efficacy and safety of aclidinium bromide in the maintenance treatment of COPD was investigated in two randomised, placebo-controlled, double-blind phase III studies of similar design: the ACCORD COPD I study (n=561) assessed patients over 12 weeks and the ATTAIN study (n=828) evaluated patients over 24 weeks.2,3
In both studies, patients with moderate to severe COPD were randomised (1:1:1) to receive twice-daily doses of aclidinium bromide 200 microgram, 400 microgram or placebo, all administered using a proprietary dry powder inhaler (Genuair).2,3
Investigators used the change from baseline in trough forced expiratory volume in one second (FEV1) as the primary efficacy endpoint. Peak FEV1 at trial end was the secondary endpoint.2,3
To evaluate the effect of treatment on quality of life, investigators measured health status using the St George’s Respiratory Questionnaire (SGRQ). In addition, clinical COPD symptoms were assessed using the Transitional Dyspnoea Index (TDI).2,3
At trial end, the 400 microgram twice-daily metered dose of aclidinium bromide (which corresponds to a delivered dose of 322 microgram aclidinium) provided a significant improvement from baseline in mean trough FEV1 compared with placebo: 124ml in the ACCORD COPD I study and 128ml in the ATTAIN study (p<0.0001 for both). Peak FEV1 was also significantly increased: by 192ml and 209ml, respectively (p<0.0001 for both).2,3
Clinically meaningful improvements in SGRQ score (≥4 point decrease from baseline) and TDI (≥1 unit increase from baseline) were observed for both doses in both studies (p<0.001 for all comparisons). Also, patients in both studies treated with the 400 microgram twice-daily dose had a reduced need for rescue medication by an average of around one inhalation per day over the treatment period.2,3
In a pooled analysis of the two trials, the 400 microgram twice-daily dose significantly reduced the rate of moderate to severe exacerbations (ie, those requiring hospitalisation or treatment with antibiotics or corticosteroids) compared with placebo (0.31 vs 0.44 per patient per year; p=0.0149).1
Aclidinium bromide was well tolerated in both studies, with most adverse events being mild to moderate in severity. The most commonly observed side-effect in all groups was exacerbation of COPD symptoms. The incidence of anticholinergic side-effects was similar across all treatment arms. Other effects reported more commonly in patients who received aclidinium bromide included headache, diarrhoea, cough, rhinitis and nasopharyngitis.1–3
In a study in healthy individuals, inhalation of aclidinium bromide 200 or 800 microgram once daily for 3 days had no clinically significant effects on QT interval. Additionally, no effects on cardiac rhythm were seen in a 3-month study using a dose of 400 microgram twice daily.1
As with other inhaled therapies, aclidinium bromide can cause paradoxical bronchospasm; if this occurs, treatment should be stopped and alternative therapy considered. Owing to its anticholinergic properties, aclidinium bromide should be used with caution in patients with BPH, bladder-neck obstruction or narrow-angle glaucoma.1
Aclidinium bromide is presented in the Genuair device, which provides confirmation to the patient of successful inhalation. It also includes a dose indicator, a safety mechanism to prevent double dosing and an end-of-dose lockout mechanism to prevent use of the empty device.1
- Eklira Genuair Summary of Product Characteristics, July 2012.
- Kerwin EM et al. COPD 2012; 9: 90-101.
- Jones PW et al. Eur Respir J 2012, accepted article; DOI: 10.1183/09031936.00225511.
Further information: Almirall