Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study
Article first published online: 28 JAN 2010
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 69, Issue 5, pages 458–464, May 2010
How to Cite
Schelfhout, V. J., Ferrer, P., Jansat, J. M., Peris, F., Gil, E. G., Pauwels, R. A. and Joos, G. F. (2010), Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study. British Journal of Clinical Pharmacology, 69: 458–464. doi: 10.1111/j.1365-2125.2010.03622.x
- Issue published online: 12 APR 2010
- Article first published online: 28 JAN 2010
- Received 22 June 2009Accepted15 December 2009
- phase I
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Long-acting inhaled bronchodilators are central in the symptomatic treatment of patients with chronic obstructive pulmonary disease (COPD). Until now the only long-acting inhaled anticholinergic drug available in the clinic is tiotropium bromide.
WHAT THIS STUDY ADDS
• Aclidinium bromide is a new anticholinergic drug. In normal volunteers inhalation of this compound induced a long-lasting bronchodilation and offered protection against the bronchoconstrictor effect of inhaled methacholine. Aclidinium bromide is now being developed as a long-acting anticholinergic for patients with COPD.
AIM Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction.
METHODS This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 µg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine).
RESULTS Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean ± SD AUC (l kPa−1 h) for placebo 24.4 ± 4.37, for 50 µg 29.0 ± 7.08, for 300 µg 31.2 ± 6.68 and for 600 µg 32.7 ± 7.95) (P < 0.009), except 50 µg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 µg compared with placebo at all assessments (Raw mean ± SD AUC (kPa s−1 l−1 h) for placebo 7.7 ± 3.46, for 300 µg 5.8 ± 2.33, for 600 µg 6.3 ± 3.11) (P < 0.04) except 600 µg at 24 h. Differences between aclidinium 300 and 600 µg vs. placebo in PC35 doubling concentration were significant at all assessments (mean ± SD AUC (mg ml−1 h) for placebo 100.0 ± 30.27, for 50 µg 117.2 ± 33.33, for 300 µg 168.9 ± 28.66 and for 600 µg 179.1 ± 15.73 (P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 µg and the higher doses (P < 0.0001). Aclidinium was not detected in plasma and was well tolerated.
CONCLUSION Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD.