title: Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study.
abstract: BACKGROUND
  Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.
  
  
  METHODS
  In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.
  
  
  RESULTS
  At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.
  
  
  CONCLUSIONS
  Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01462942.
authors.affiliation: University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9QZ, UK. dsingh@meu.org.uk.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Korn
authors.forename: Cristina
authors.initials: C
authors.lastname: Serra
authors.forename: Eduard
authors.initials: E
authors.lastname: Molins
authors.forename: Cynthia
authors.initials: C
authors.lastname: Caracta
authors.forename: Esther Garcia
authors.initials: EG
authors.lastname: Gil
authors.forename: Anne
authors.initials: A
authors.lastname: Leselbaum
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D004417:Dyspnea / Q000209:etiology; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012720:Severity of Illness Index; D014326:Tropanes / Q000008:administration & dosage* / Q000009:adverse effects*; D014797:Vital Capacity
chemical_list: D004338:Drug Combinations; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate