Cardiovascular Safety of QVA149, a Combination of Indacaterol and NVA237, in COPD Patients

ABSTRACT

This study assessed the cardiovascular safety of QVA149, an inhaled, once daily, bronchodilator combination containing two 24-hour bronchodilators, the long-acting β₂-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237). In this randomised, double-blind, placebo-controlled, parallel-group study, 257 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) were randomised to receive QVA149 (indacaterol/NVA237) 600/100 μg, 300/100 μg or 150/100 μg, indacaterol 300 μg or placebo, once daily for 14 days. The primary endpoint was change from baseline in 24-h mean heart rate versus placebo on Day 14. 255 patients were included in the safety analysis (mean age 63.8 years, 76.5% male, post-bronchodilator forced expiratory volume in one second [FEV₁] 53.2% predicted, FEV₁/FVC [forced vital capacity] 50.0%, mean 24-h heart rate 79.6 bpm). There were no clinically significant differences in the 24-h mean heart rate on Day 14 between the three doses of QVA149 and placebo or indacaterol. The confidence intervals of these treatment differences (contrasts) were within the pre-specified equivalence limit (-5 to 5 bpm). No clinically relevant differences in QTc interval (Fridericia's) were observed between groups on Days 1, 7 and 14. Once-daily QVA149 was well tolerated in COPD patients with a cardiovascular safety profile and overall adverse event rates similar to placebo.

Keywords: :

• Cardiovascular safety
• COPD
• NVA237
• QVA149
• Indacaterol
• Glycopyrronium

ACKNOWLEDGMENTS

The authors acknowledge Shaik Asma Sultana, professional medical writer (Novartis), Mark Fedele (Novartis) and Gary Cotter (ACUMED UK) for assistance in the preparation of this manuscript. This study was supported by Novartis Pharma AG, Basel, Switzerland.

Notes

*Breezhaler is a registered trademark of Novartis Pharm AG, Basel, Switzerland.