title: Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Patients With COPD.
abstract: BACKGROUND
  Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD.
  
  
  METHODS
  These two phase III trials took place over 24 weeks and were randomized, double blind, and placebo controlled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed.
  
  
  RESULTS
  At week 24, differences in change from baseline in the morning predose trough FEV1for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms).
  
  
  CONCLUSIONS
  We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov.
authors.affiliation: Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medicine, New York, NY. Electronic address: fjm2003@med.cornell.edu.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; and Department of Medicine, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.affiliation: Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
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: Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.affiliation: Clinical Discovery Unit, Early Clinical Development, AstraZeneca, Cambridge, UK; and S. Carolina Pharmaceutical Research, North Grove Medical Park, Spartanburg, SC.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Feldman
authors.affiliation: Department of Medicine, University at Buffalo, SUNY, Buffalo, NY.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Charlotte Lung and Health, American Health Research, Inc., Charlotte, NC.
authors.forename: Selwyn
authors.initials: S
authors.lastname: Spangenthal
authors.affiliation: New Horizons Clinical Research, Cincinnati, OH.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Gottschlich
authors.affiliation: Servei de Pneumologia, Institut Clinic Respiratori, Hospital Clínic; and University of Barcelona, Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.affiliation: Aventiv Research, Columbus, OH.
authors.forename: Samir
authors.initials: S
authors.lastname: Arora
authors.affiliation: Midwest Chest Consultants, St. Charles, MO.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Siler
authors.affiliation: Respiratory, AstraZeneca, Gaithersburg, MD (former employee of Pearl Therapeutics, Inc.).
authors.forename: Shahid
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Biostatistics, Pearl Therapeutics, Inc., Morristown, NJ.
authors.forename: Patrick
authors.initials: P
authors.lastname: Darken
authors.affiliation: Regulatory Affairs, Pearl Therapeutics, Inc., Durham, NC.
authors.forename: Tracy
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Biostatistics, Pearl Therapeutics, Inc., Morristown, NJ.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maes
authors.affiliation: Regulatory Affairs and Quality, Pearl Therapeutics, Inc., Durham, NC.
authors.forename: Michael
authors.initials: M
authors.lastname: Golden
authors.affiliation: Clinical Development, Pearl Therapeutics, Inc., Morristown, NJ.
authors.forename: Chad
authors.initials: C
authors.lastname: Orevillo
authors.affiliation: Clinical Development, Pearl Therapeutics, Inc., Morristown, NJ.
authors.forename: Colin
authors.initials: C
authors.lastname: Reisner
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000627:therapeutic use; D006024:Glycopyrrolate / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D011241:Prednisone / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013535:Suspensions; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D005938:Glucocorticoids; D018727:Muscarinic Antagonists; D013535:Suspensions; D019819:Budesonide; D000068298:Fluticasone; D006024:Glycopyrrolate; D011241:Prednisone; D000068759:Formoterol Fumarate
keywords: bronchodilator; chronic bronchitis; emphysema; muscarinic antagonists; β(2)-agonist