title: Efficacy and safety of twice-daily glycopyrrolate in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation: the GEM1 study.
abstract: BACKGROUND
  The purpose of this study was to confirm the efficacy and safety of twice-daily glycopyrrolate 15.6 µg, a long-acting muscarinic antagonist, in patients with stable, symptomatic, chronic obstructive pulmonary disease (COPD) with moderate-to-severe airflow limitation.
  
  
  METHODS
  The GEM1 study was a 12-week, multicenter, double-blind, parallel-group, placebo-controlled study that randomized patients with stable, symptomatic COPD with moderate-to-severe airflow limitation to twice-daily glycopyrrolate 15.6 µg or placebo (1:1) via the Neohaler(®) device. The primary objective was to demonstrate superiority of glycopyrrolate versus placebo in terms of forced expiratory volume in 1 second area under the curve between 0 and 12 hours post morning dose at week 12. Other outcomes included additional spirometric end points, transition dyspnea index, St George's Respiratory Questionnaire, COPD Assessment Test, rescue medication use, and symptoms reported by patients via electronic diary. Safety was also assessed during the study.
  
  
  RESULTS
  Of the 441 patients randomized (glycopyrrolate, n=222; placebo, n=219), 96% of patients completed the planned treatment phase. Glycopyrrolate demonstrated statistically significant (P<0.001) improvements in lung function versus placebo. Glycopyrrolate showed statistically significant improvement in the transition dyspnea index focal score, St George's Respiratory Questionnaire total score, COPD Assessment Test score, rescue medication use, and daily total symptom score versus placebo at week 12. Safety was comparable between the treatment groups.
  
  
  CONCLUSIONS
  Significant improvement in lung function, dyspnea, COPD symptoms, health status, and rescue medication use suggests that glycopyrrolate is a safe and effective treatment option as maintenance bronchodilator in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation.
authors.affiliation: North Carolina Clinical Research, Raleigh, NC, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: LaForce
authors.affiliation: South Carolina Pharmaceutical Research, Spartanburg, SC, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Feldman
authors.affiliation: American Health Research, Charlotte, NC, USA.
authors.forename: Selwyn
authors.initials: S
authors.lastname: Spangenthal
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Joerg H
authors.initials: JH
authors.lastname: Eckert
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Henley
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patalano
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: D'Andrea
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006304:Health Status; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate
keywords: bronchodilator; chronic obstructive pulmonary disease; glycopyrrolate; glycopyrronium; long-acting muscarinic antagonist; lung function; twice daily