Objective: The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 μg/2 mL twice daily (ARF15 BID) and 30 μg/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 ≥45 years with moderate to severe COPD, a forced expiratory volume in 1 second (FEV1) ≥0.7 L, and ≤65% predicted FEV1, and a FEV1:forced vital capacity ratio ≤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 FEV1 from baseline (hour 0) to 24 hours (FEV1AUC0-24). Secondary efficacy end points were time-normalized AUC of FEV1 from baseline to 12 hours (FEV1AUC0-12) and from 12 to 24 hours (FEV1AUC12-24), and FEV1 at 24 hours after administration of the morning dose (trough FEV1). 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 FEV1AUC0-24 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 (FEV1AUC0-24, LSM 0.15 and 0.16 L, respectively; Δ, 0.01 L; 90% CI, -0.02 to 0.04) and trough FEV1 (LSM, 0.15 and 0.12 L, respectively; Δ, -0.03 L; 90% CI, -0.09 to 0.03). FEV1AUC0-12 was improved more with ARF30 QD than ARF15 BID (Δ, 0.06 L; 90% CI, 0.04 to 0.09), and FEV1AUC12-24 was improved more with ARF15 BID than ARF30 Qd (Δ, -0.04 L; 90% CI, -0.08 to 0.01). The 90% CI for FEV1AUC0-24 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 FEV1AUC0-24 values. Conclusions: In these subjects with moderate to severe COPD, single-day administrations of ARF15 BID or ARF30 QD were associated with FEV1 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.
All Science Journal Classification (ASJC) codes
- Pharmacology (medical)
- chronic obstructive pulmonary disease
- dosing regimen
- long-acting β-agonist