title: Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated inhaler vs pMDI.
abstract: BACKGROUND
  To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 μg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI).
  
  
  METHODS
  This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 μg bid, BUD/FM pMDI 2 × 160/4.5 μg bid, or BUD pMDI 2 × 160 μg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV1 (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1 within confidence intervals (CIs) of 80-125%.
  
  
  RESULTS
  Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI, 0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar.
  
  
  CONCLUSIONS
  BUD/FM 2 × 160/4.5 μg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting β2-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.
authors.affiliation: Allergy, Asthma, and Pulmonary Research, Boys Town National Research Hospital, Department of Pediatrics, University of Nebraska Medical Center, Creighton University School of Medicine, Omaha, NE 68132, United States. Electronic address: Kevin.Murphy@boystown.org.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Murphy
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, U114, Knoxville, TN 37920, United States.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhand
authors.affiliation: AstraZeneca LP, 1800 Concord Pike, Wilmington, DE 19850, United States.
authors.forename: Frank
authors.initials: F
authors.lastname: Trudo
authors.affiliation: AstraZeneca LP, 1800 Concord Pike, Wilmington, DE 19850, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Uryniak
authors.affiliation: AstraZeneca LP, 1800 Concord Pike, Wilmington, DE 19850, United States.
authors.forename: Ajay
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: AstraZeneca, Pepparedsleden 1, Mölndal, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Eckerwall
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D002031:Bulgaria; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D006801:Humans; D006814:Hungary; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide; D000068759:Formoterol Fumarate
keywords: Asthma; Breath-actuated; Budesonide; Formoterol; Inhaler; Pressurized metered-dose