title: A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD.
abstract: BACKGROUND
  Formoterol fumarate (FF) is a well-established long-acting β2-agonist. This represents the first clinical study of FF in a metered-dose inhaler (FF MDI) based on proprietary lipid-based porous-particle engineering technology.
  
  
  METHODS
  In this randomized, double-blind, 5-period, crossover study (NCT00880490), subjects received 2.4, 4.8, and 9.6 μg of FF MDI, open-label Foradil(®) Aerolizer(®) (FA) 12 μg, and placebo. Spirometry was performed at baseline, 15 and 30 min, and 1, 2, 4, 6, 8, 10, 11.5, and 12 h post-dose.
  
  
  RESULTS
  Thirty-four subjects were enrolled. Improvement in forced expiratory volume in 1 s (FEV1) was similar between FF MDI 9.6 μg and FA. Change in FEV1 area under the curve for 0-12 h (AUC0-12) for each FF MDI dose demonstrated superior efficacy versus placebo (P < .001 for all 3 doses). Over 12 h and at each time point, FF MDI 9.6 μg was non-inferior to FA for FEV1 AUC0-12 with the 95% CI's supporting a maximum difference of approximately 45 mL. Peak and trough FEV1, forced vital capacity, peak expiratory flow rate, peak inspiratory capacity, and pharmacokinetics confirmed the primary endpoint, with dose ordering of the FF MDI 2.4, 4.8, and 9.6 μg, and comparability of FF MDI 9.6 μg to FA. All 3 doses of FF MDI were safe and well-tolerated, with a safety profile similar to that of placebo and FA.
  
  
  CONCLUSIONS
  The efficacy and pharmacokinetic profile of FF MDI 9.6 μg were comparable to FA 12 μg and with similar safety to placebo and FA.
  
  
  BACKGROUND
  This clinical trial was registered on ClinicalTrials.gov, Identifier: NCT NCT00880490.
authors: P3 Research Ltd., First Floor 121 Adelaide Road, Newtown, Wellington 6021, New Zealand. Electronic address: dean@p3research.co.nz.
authors: Dean
authors: D
authors: Quinn
authors: Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, Sydney, NSW 2037, Australia. Electronic address: jpseale@pharmacol.usyd.edu.au.
authors: J P
authors: JP
authors: Seale
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: creisner@pearltherapeutics.com.
authors: Colin
authors: C
authors: Reisner
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: tfischer@pearltherapeutics.com.
authors: Tracy
authors: T
authors: Fischer
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: mgolden@pearltherapeutics.com.
authors: Michael
authors: M
authors: Golden
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: cfernandez@pearltherapeutics.com.
authors: Carlos
authors: C
authors: Fernandez
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: pdarken@pearltherapeutics.com.
authors: Patrick
authors: P
authors: Darken
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: estrose@pearltherapeutics.com.
authors: Earl
authors: E
authors: St Rose
authors: Emphron Informatics Pty Ltd, Level 3, 88 Jephson St, Toowong, Queensland 4066, Australia. Electronic address: mervyn.thomas@emphron.com.
authors: Mervyn
authors: M
authors: Thomas
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: gtardie@pearltherapeutics.com.
authors: Gregory
authors: G
authors: Tardie
authors: Pearl Therapeutics, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ 07960, USA. Electronic address: corevillo@pearltherapeutics.com.
authors: Chadwick
authors: C
authors: Orevillo
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D016062:Porosity; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate
keywords: Chronic obstructive pulmonary disease; Formoterol fumarate MDI; Porous particle technology