title: Evaluation of the efficacy and safety of levalbuterol in subjects with COPD.
abstract: The efficacy and safety of nebulized levalbuterol in adults with chronic obstructive pulmonary disease (COPD) was evaluated in this multicenter, randomized, double-blind, parallel design study. Randomized subjects (n = 209) received levalbuterol (LEV) 0.63 mg or 1.25 mg, racemic albuterol (RAC) 2.5 mg, or placebo (PBO) TID for 6 weeks. Serial spirometry was completed in-clinic after study drug alone (weeks 0, 2, and 6) or in combination with ipratropium bromide 0.5 mg (week 4). The primary endpoint was the averaged FEV1 AUC(0-8 hrs) over weeks 0, 2 and 6 compared with placebo. Other endpoints included rescue medication use, safety parameters, COPD exacerbations, and global evaluations. All active treatments demonstrated improvements in the percent change in FEV1 AUC(0-8 hrs) over the double-blind period and at each visit vs PBO (p < 0.05). Rescue medication use vs. baseline (doses/day) changed over time: PBO +0.38 +/- 3.3; LEV 0.63 mg +0.07 +/- 3.3; LEV 1.25 mg -0.84 +/- 3.8 (p = 0.02 vs. RAC); RAC +0.97 +/- 2.5. The overall rate of adverse events was PBO 56.4%, LEV 0.63 mg 56.6%, LEV 1.25 mg 67.3%, and RAC 65.4%. Protocol-defined COPD exacerbations occurred in all groups (PBO 12.7%, LEV 0.63 mg 11.3%; LEV 1.25 mg 18.4%; RAC 21.2%). Withdrawals due to COPD exacerbations were significantly higher in the RAC group compared with PBO (PBO 0%; LEV 0.63 mg 1.9%; LEV 1.25 mg 4.1%; RAC 9.6% p = 0.01 vs. PBO). In this study, levalbuterol treatment in subjects with COPD was generally well tolerated, produced significant bronchodilation compared with PBO, and improved clinical control of COPD as evidenced by reductions in rescue medication use compared with PBO and/or RAC.
authors.affiliation: University of North Carolina School of Medicine at Chapel Hill, USA. jdonohue@med.unc.edu
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.forename: Merdad V
authors.initials: MV
authors.lastname: Parsey
authors.forename: Charles
authors.initials: C
authors.lastname: Andrews
authors.forename: Tony
authors.initials: T
authors.lastname: D'Urzo
authors.forename: Satyendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Kendyl
authors.initials: K
authors.lastname: Schaefer
authors.forename: Raymond
authors.initials: R
authors.lastname: Claus
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Baumgartner
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D000420:Albuterol