title: A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease.
abstract: Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI).
  
  
  
  This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD ( NCT01085045 ). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1AUC0-12) on Day 7 relative to baseline FEV1. Secondary endpoints included pharmacokinetics and safety.
  
  
  
  GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV1AUC0-12after 7 days' treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated.
  
  
  
  GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.
  
  
  
  ClinicalTrials.gov NCT01085045 . Registered 9 March 2010.
authors.affiliation: Pearl Therapeutics Inc., 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ, 07960, USA. creisner@pearltherapeutics.com.
authors.forename: Colin
authors.initials: C
authors.lastname: Reisner
authors.affiliation: Department of Medicine, University of Modena and Reggio Emilia, NOCSAE, Modena, Italy.
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
authors.affiliation: Clinical Research Institute of Southern Oregon, Medford, OR, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.affiliation: Spartanburg Medical Research, Spartanburg, NC, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Fogarty
authors.affiliation: American Health Research, Charlotte, NC, USA.
authors.forename: Selwyn
authors.initials: S
authors.lastname: Spangenthal
authors.affiliation: Lungen Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.|Department of Medicine, Christian-Albrechts University Kiel, Kiel, MI, USA.
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.affiliation: Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College; New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.affiliation: Pearl Therapeutics Inc., 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ, 07960, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Darken
authors.affiliation: Pearl Therapeutics Inc., 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ, 07960, USA.
authors.forename: Earl
authors.initials: E
authors.lastname: St Rose
authors.affiliation: Pearl Therapeutics Inc., 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ, 07960, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Orevillo
authors.affiliation: Pearl Therapeutics Inc., Durham, NC, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Strom
authors.affiliation: Pearl Therapeutics Inc., Durham, NC, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Pearl Therapeutics Inc., Durham, NC, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Golden
authors.affiliation: Pearl Therapeutics Inc., Redwood City, CA, USA.
authors.forename: Sarvajna
authors.initials: S
authors.lastname: Dwivedi
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001315:Australia; D004311:Double-Blind Method; D004338:Drug Combinations; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009520:New Zealand; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate; D000068759:Formoterol Fumarate
keywords: Bronchodilators; COPD; COPD maintenance; Co-Suspension™ Delivery Technology; LABA; LAMA; Lung function; Metered dose inhaler