title: Bronchodilatory effects of NVA237, a once daily long-acting muscarinic antagonist, in COPD patients.
abstract: NVA237 is a novel, once daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This study aimed to assess the 24-h bronchodilatory effect following 14 days of treatment with inhaled NVA237 in patients with mild, moderate or severe COPD. This was a randomized, double-blind, placebo-controlled, two-period, crossover, multicenter study. A total of 33 patients (≥ 40 years; smoking history of ≥ 10 pack-years) were randomized to receive NVA237 50 μg once daily followed by placebo or placebo followed by NVA237 50 μg for 14 days. Treatment periods were separated by a 7-14 day washout period. The primary variable was the mean forced expiratory volume in 1 s (FEV(1)) derived from the area under the curve (AUC) between 0 and 24 h post-dose on Day 14. The 24-h FEV(1) profiles showed a consistent bronchodilator effect for NVA237 versus placebo on Day 14. Least square (LS) mean difference in FEV(1) AUC(0-24 h) values between NVA237 and placebo was 163 mL (P < 0.001). There were significant increases in mean FEV(1) AUC(0-12 h) (LS mean difference 165 mL, P = 0.001) and FEV(1) AUC(12-24 h) (161 mL, P < 0.001) versus placebo. NVA237 significantly improved peak FEV(1) (by 208 mL, P < 0.001) and trough FEV(1) (by 154 mL, P = 0.003) versus placebo on Day 14. NVA237 was well tolerated; all adverse events were mild or moderate in intensity and not related to study drug. NVA237 50 μg once daily was well tolerated and showed significant and sustained 24-h bronchodilation in patients with COPD.
authors.affiliation: Spartanburg Medical Research, Spartanburg, SC, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Fogarty
authors.forename: Helen
authors.initials: H
authors.lastname: Hattersley
authors.forename: Lilla
authors.initials: L
authors.lastname: Di Scala
authors.forename: Anton
authors.initials: A
authors.lastname: Drollmann
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects* / Q000502:physiology; D006024:Glycopyrrolate / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013147:Spirometry; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate