title: Early bronchodilator action of glycopyrronium versus tiotropium in moderate-to-severe COPD patients: a cross-over blinded randomized study (Symptoms and Pulmonary function in the moRnING).
abstract: BACKGROUND
  Morning symptoms associated with COPD have a negative impact on patients' quality of life. Long-acting bronchodilators with rapid onset may relieve patients' symptoms. In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD.
  
  
  METHODS
  Patients were randomized (1:1) to receive either once-daily GLY (50 μg) or TIO (18 μg) and corresponding placebos in a cross-over design for 28 days. The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours (AUC0-4h) forced expiratory volume in 1 second (FEV1) after the first dose. The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation.
  
  
  RESULTS
  One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7 years) and 108 patients completed the study. On Day 1, GLY resulted in significantly higher FEV1 AUC0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004-0.056, P=0.025). Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO. Post hoc analysis of the FEV1 AUC0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P=0.026), and 1 hour (Δ=0.044 L, P=0.014). Safety results were comparable between both treatments.
  
  
  CONCLUSIONS
  The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO.
authors.affiliation: University Hospital Miguel Servet, IISAragón, CIBERES, Zaragoza, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Marin
authors.affiliation: Insaf Respiratory Research Institute, Wiesbaden, Germany.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Beeh
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Clemens
authors.affiliation: Hospital Piero Palagi, Fiorenze, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Castellani
authors.affiliation: Research Institute and Practice, Berlin-Brandenburg, Germany.
authors.forename: Lennart
authors.initials: L
authors.lastname: Schaper
authors.affiliation: Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Saralaya
authors.affiliation: Staploe Medical Center, Soham, Cambridge, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gunstone
authors.affiliation: Novartis Farmaceutica SA, Barcelona, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Casamor
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostikas
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Maryam
authors.initials: M
authors.lastname: Aalamian-Mattheis
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000071066:Patient Reported Outcome Measures; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: COPD; LAMA; fast onset; glycopyrronium; lung function; patient reported outcome; rapid onset; tiotropium