SESSION TITLE: New treatments for COPD
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 28, 2013 at 01:45 PM - 03:15 PM
PURPOSE: Dose-ranging study to evaluate efficacy and safety of 2 fixed-dose combinations (FDC) of aclidinium, a long-acting muscarinic antagonist (LAMA) approved for long-term maintenance treatment of bronchospasm associated with COPD, plus formoterol, a long-acting β2-agonist (LABA), compared with aclidinium, formoterol, and placebo administered twice daily (BID) via the PressairTM/Genuair® inhaler in COPD patients.
METHODS: This was a randomized, double-blind, 4-period, incomplete, crossover study with 14-day blocks of treatment with aclidinium 400µg + formoterol 12µg (FDC 400/12), aclidinium 400µg + formoterol 6µg (FDC 400/6), aclidinium 400µg, formoterol 12µg, or placebo, with 7-10-day washouts between blocks. The primary outcome was change from baseline to Day 14 in normalized FEV1 area under the curve from 0-12 hours (AUC0-12) and secondary outcomes were morning predose (trough) and peak FEV1. Safety was also assessed.
RESULTS: All treatment groups (N=128) had significant improvements from baseline to Day 14 in FEV1 AUC0-12 over placebo (FDC 400/12, 200mL; FDC 400/6, 202mL; aclidinium, 157mL; formoterol, 127mL; all p<0.0001). Both FDC groups showed significant improvements from baseline in FEV1 AUC0-12 vs formoterol (p<0.01); FDC 400/6 had a significant increase vs aclidinium alone (p<0.05). For trough FEV1, FDC 400/12 and FDC 400/6 showed statistically and clinically significant improvements from baseline over placebo (132mL and 137mL, respectively; p<0.0001) and statistically significant increases over formoterol (53mL and 57mL, respectively; p<0.05). FDC 400/6 led to a significantly greater increase from baseline than aclidinium (49mL, p<0.05). Aclidinium and formoterol monotherapies also led to significant improvements from baseline over placebo (88mL and 79mL, respectively; p<0.01). For peak FEV1, changes from baseline were significantly higher for both FDC groups over placebo, formoterol, and aclidinium (all p<0.001). Both FDCs and monotherapies were well-tolerated, with similar safety profiles across groups. Few serious adverse events were observed and no deaths were reported.
CONCLUSIONS: In this study, the fixed-dose combinations of aclidinium 400µg plus formoterol 12µg or 6µg BID significantly improved lung function over placebo, formoterol, and aclidinium, and both were well tolerated.
CLINICAL IMPLICATIONS: Further studies on the fixed-dose LAMA/LABA combinations of aclidinium and formoterol in the treatment of COPD are ongoing as this may be a valuable new treatment option.
DISCLOSURE: Edward Kerwin: Other: Edward Kerwin has received travel reimbursement from Merck, Forest, and Novartis, and has performed multicenter clinical trials for multiple pharmaceutical companies including Forest and Almirall, S.A. Anne Leselbaum: Employee: Almirall S.A. Stephan Ortiz: Employee: Forest Research Institute Paul Rowe: Employee: Forest Research Institute Cynthia Caracta: Employee: Forest Research Institute The following authors have nothing to disclose: Robert Lapidus
Aclidinium bromide/formoterol via the PressairTM/Genuair® inhaler are in clinical development and have not yet been approved for commercial use in the treatment of COPD.