Abstract
BACKGROUND: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers. METHODS: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV(1)) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo. RESULTS: Maximum change in FEV(1) with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV(1) during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV(1). All subjects with both doses of imidafenacin completed without moderate nor severe adverse events. CONCLUSION: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD. TRIAL REGISTRATION: JapicCTI-121760 (Japan Pharmaceutical Information Center - Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).