QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease
- Jan A van Noord1,
- Roland Buhl2,
- Craig LaForce3,
- Carmen Martin4,
- Francis Jones4,
- Michael Dolker5,
- Tim Overend4
- 1Department of Respiratory Diseases, Atrium Medisch Centrum, Heerlen, The Netherlands
- 2Pulmonary Department, Mainz University, Mainz, Germany
- 3North Carolina Clinical Research, Raleigh, North Carolina, USA
- 4Novartis Horsham Research Centre, West Sussex, UK
- 5Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
- Correspondence to Dr Jan A van Noord, Department of Respiratory Diseases, Atrium Medisch Centrum, Heerlen, The Netherlands;
- Received 30 March 2010
- Accepted 2 September 2010
- Published Online First 26 October 2010
Background This randomised, double-blind, placebo controlled, four-period crossover study assessed the efficacy and safety of once-daily QVA149, a dual bronchodilator consisting of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Methods Patients (N=154) were randomly assigned to receive QVA149 (indacaterol/NVA237) 300/50 μg, indacaterol 300 μg, indacaterol 600 μg, or placebo, once daily for 7 days with a 7-day washout period between each treatment. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) (mean of 23 h 15 min and 23 h 45 min post-dose values) on day 7. Other endpoints included trough FEV1 on day 1, individual time point FEV1 and monitoring and recording of all adverse events.
Results A total of 135 (87.7%) patients completed the study (all randomly assigned patients: mean age 61.7 years, 61.4% male, post-bronchodilator FEV1 52.2% predicted, FEV1/forced vital capacity 47.6%). The estimated treatment difference (95% CI) for trough FEV1 on day 7 between QVA149 and placebo was 226 ml (192 to 260; p<0.001). The estimated treatment difference between QVA149 and indacaterol 300 and 600 μg was 123 ml (89 to 157; p<0.001) and 117 ml (83 to 150; p<0.001), respectively. The improvements in mean trough FEV1 exceeded the predefined minimal clinically important differences of 100–140 ml for QVA149 versus placebo and indacaterol. Similar results were observed on day 1. All treatments were well tolerated.
Conclusions QVA149 demonstrated rapid and sustained bronchodilation with significant improvements compared with indacaterol monotherapy and placebo in patients with COPD.
Clinical trial registration NCT00570778.
Funding This study was funded entirely by Novartis.
Competing interests JAvN is involved in carrying out contract research for Boehringer Ingelheim, GSK and Chiesi. RB has received reimbursement for attending scientific conferences, and/or fees for speaking and/or consulting from Novartis. He also has similar relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Nycomed. CL is a member of the speaker's bureau for the following organisations: AstraZeneca, GlaxoSmithKline, Merck, Novartis, UCB Pharma, Sanofi-Aventis and Sepracor. He is also on the advisory boards at: GlaxoSmithKline, Schering-Plough, Alcon and Sepracor. CM, FJ, MD and TO are employees of Novartis.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the independent ethics committee orinstitutional review board for each participating study centre.
Provenance and peer review Not commissioned; externally peer reviewed.