Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study

Respir Med. 2013 Oct;107(10):1558-67. doi: 10.1016/j.rmed.2013.05.016. Epub 2013 Jul 16.

Abstract

Background: QVA149 is an inhaled, once-daily fixed-dose dual bronchodilator combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium (NVA237) for the treatment of chronic obstructive pulmonary disease (COPD). We investigated the safety and efficacy of QVA149 over 52 weeks.

Methods: This 52-week, multicenter, double-blind, parallel-group, placebo-controlled study randomized (2:1) patients with moderate-to-severe COPD to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or placebo delivered via the Breezhaler device. Primary endpoint was safety and tolerability for treatment-emergent adverse events (AEs). Secondary endpoints included safety based on vital signs, electrocardiograms (ECGs), laboratory evaluations, and pre-dose forced expiratory volume in 1 s (FEV1).

Results: Of 339 patients randomized, QVA149 [n = 226], placebo [n = 113]; 76.9% male, mean age: 62.6 years, post-bronchodilator FEV1: 57.4% predicted, 83.5% completed study. A smaller percentage of patients discontinued in the QVA149 group (14.2%) compared with placebo (21.2%). Overall incidence of AEs was similar in the QVA149 (57.8%) and placebo (56.6%) groups, with most AEs being mild to moderate in severity. The numerical differences in some AEs observed could be at least in part explained by differences in baseline patient characteristics. No clinically relevant differences were observed between treatment groups for vital signs or ECG parameters. The five deaths reported were unrelated to study medication (QVA149, n = 4 [1.8%]; placebo, n = 1 [0.9%]). QVA149 demonstrated rapid and clinically meaningful bronchodilation sustained over 52 weeks versus placebo.

Conclusion: QVA149 demonstrated a good safety and tolerability profile, providing rapid and sustained bronchodilation over 52 weeks in patients with moderate-to-severe COPD. ClinicalTrials.gov identifier: NCT01120717.

Keywords: Bronchodilators; Chronic obstructive pulmonary disease; Lung function; QVA149; Safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Aged
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Glycopyrrolate / adverse effects
  • Glycopyrrolate / analogs & derivatives*
  • Glycopyrrolate / therapeutic use
  • Humans
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Male
  • Medication Adherence / statistics & numerical data
  • Middle Aged
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • Spirometry
  • Treatment Outcome
  • Vital Capacity / drug effects

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Indans
  • Muscarinic Antagonists
  • Quinolones
  • indacaterol-glycopyrronium combination
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT01120717