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Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial

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      Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.


      Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.


      A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV 1] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo ( P < 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV 1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo ( P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo.


      NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV 1 and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. ( Identifier: NCT01154127).

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      Author and article information

      [1 ]insaf Respiratory Research Institute, Wiesbaden, Germany
      [2 ]University Of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK
      [3 ]Novartis Pharma AG, Basel, Switzerland
      Author notes
      Correspondence: Kai M Beeh, Insaf Respiratory Research Institute, Biebricher Allee 34, D-65187, Wiesbaden, Germany, Tel +49 0611 985 4347, Fax +49 0611 985 4348, Email k.beeh@
      Int J Chron Obstruct Pulmon Dis
      Int J Chron Obstruct Pulmon Dis
      International Journal of COPD
      International Journal of Chronic Obstructive Pulmonary Disease
      Dove Medical Press
      31 July 2012
      : 7
      : 503-513
      3430121 22973092 10.2147/COPD.S32451 copd-7-503
      © 2012 Beeh et al, publisher and licensee Dove Medical Press Ltd.

      This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

      Original Research

      Respiratory medicine

      nva237, fev1, lama, copd, dyspnea, exercise tolerance


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