title: Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study.
abstract: OBJECTIVE
  The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 microg/2 mL twice daily (ARF15 BID) and 30 microg/4 mL once daily (ARF30 QD) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  In this single-dose, multicenter, randomized, modified-blind, 2-way crossover study, subjects aged > or =45 years with moderate to severe COPD, a forced expiratory volume in 1 second (FEV(1)) > or =0.7 L, and < or =65% predicted FEV1, and a FEV(1):forced vital capacity ratio < or =70% were randomly assigned to receive single-day treatment with ARF15 BID or ARF30 QD in random order, separated by a 5 +/- 2-day washout period. The primary efficacy end point was time-normalized AUC of FEV(1) from baseline (hour 0) to 24 hours (FEV(1)AUC(0-24)). Secondary efficacy end points were time-normalized AUC of FEV(1) from baseline to 12 hours (FEV(1)AUC(0-12)) and from 12 to 24 hours (FEV(1)AUC(12-24)), and FEV(1) at 24 hours after administration of the morning dose (trough FEV(1)). Equivalence of the 2 therapies was assessed by comparing the 90% CI value for the difference of the least squares mean (LSM) to a study-specific predefined equivalence range for change in FEV(1)AUC(0-24) of -0.07 to 0.07 L.
  
  
  RESULTS
  A total of 33 subjects were enrolled (20 men, 13 women; mean [SD] age, 64.5 [8.8] years; 15 subjects received ARF15 BID first; 18 received ARF30 QD first). ARF15 BID and ARF30 QD were associated with similar improvements from baseline in (FEV(1)AUC(0-24), LSM 0.15 and 0.16 L, respectively; Delta, 0.01 L; 90% CI, -0.02 to 0.04) and trough FEV(1) (LSM, 0.15 and 0.12 L, respectively; Delta, -0.03 L; 90% CI, -0.09 to 0.03). FEV(1)AUC(0-12) was improved more with ARF30 QD than ARF15 BID (Delta, 0.06 L; 90% CI, 0.04 to 0.09), and FEV(1)AUC(12-24) was improved more with ARF15 BID than ARF30 Qd (Delta, -0.04 L; 90% CI, -0.08 to 0.01). The 90% CI for FEV(1)AUC(0-24) for the treatment difference between ARF15 BID and ARF30 QD was within the prespecified range of -0.07 to 0.07 L, indicating that both treatments resulted in equivalent FEV(1)AUC(0-24) values.
  
  
  CONCLUSIONS
  In these subjects with moderate to severe COPD, single-day administrations of ARF15 BID or ARF30 QD were associated with FEV(1) responses over a period of 24 hours that were considered equivalent per the protocol definition employed in the present study. FEV1 improvement over 12 hours was greater for ARF30 QD after the morning dose and for ARF15 BID after the evening dose. ClinicalTrials.gov Identifier: NCT00571428.
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-3403, USA. rap@mail.med.upenn.edu
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
authors.forename: Neil
authors.initials: N
authors.lastname: MacIntyre
authors.forename: Michael
authors.initials: M
authors.lastname: Sims
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.forename: Charles
authors.initials: C
authors.lastname: Fogarty
authors.forename: Michael
authors.initials: M
authors.lastname: Noonan
authors.forename: Raymond
authors.initials: R
authors.lastname: Claus
authors.forename: William T
authors.initials: WT
authors.lastname: Andrews
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate