24-hour bronchodilator efficacy of single doses of indacaterol in patients with persistent asthma: comparison with placebo and formoterol

ABSTRACT

Objective: To assess the 24-h bronchodilator efficacy and safety of single-dose indacaterol in asthma.

Methods: This was a five-period, double-blind, double-dummy, crossover study in patients with persistent asthma. On separate study days, patients inhaled a single dose of indacaterol (150, 300 or 600 µg) in the morning via a single-dose dry powder inhaler (SDDPI), formoterol 12 µg twice daily via its proprietary SDDPI, or placebo. Study days were separated by a washout period of at least 6 days.

Results: Of the 45 patients randomized to treatment, 42 completed the study. The 24-h trough FEV₁ (primary endpoint) was significantly higher than placebo following all doses of indacaterol (mean [95% CI] differences of 0.11 [0.06, 0.16], 0.21 [0.17, 0.26] and 0.22 [0.18, 0.27] L for 150, 300, and 600 µg, respectively) and formoterol (by 0.13 [0.08, 0.18] L). The 24-h trough FEV₁ was significantly higher following indacaterol 300 and 600 µg than indacaterol 150 µg (by 0.11 [0.06, 0.15] and 0.12 [0.07, 0.17] L, respectively) or formoterol (by 0.08 [0.03, 0.13] L vs. 300 µg; by 0.09 [0.04, 0.14] L vs. 600 µg). Most adverse events were mild-to-moderate and transient. Examination of serum potassium, blood glucose, QTc interval, pulse rate, and blood pressure raised no concern over the safety of indacaterol.

Conclusions: Single doses of indacaterol provided effective 24-h bronchodilation and were well tolerated in patients with persistent asthma. Safety findings were limited by non-standardized diet conditions in this study but suggest a minimal systemic treatment effect.

Keywords: :

• Asthma
• Bronchodilation
• FEV₁
• Formoterol
• Indacaterol
• Single dose

Transparency

Declaration of funding

This study was sponsored by Novartis Pharma AG.

Declaration of financial/other interests

P.O., M.H. and F.D. have disclosed that they are employees of Novartis Pharmaceuticals. C.L. has disclosed that he is a member of the speaker's bureau for the following organizations: AstraZeneca, GlaxoSmithKline, Merck, Novartis, UCB Pharma, Sanofi-Aventis, and Sepracor; and that he is on the Advisory Boards at GlaxoSmithKline, Schering-Plough, Alcon and Sepracor. P.K. has disclosed that he holds stock in: Cardinal Health, Eli Lilly, Johnson & Johnson, St. Jude Medical, Teva Specialty Pharmaceuticals and United Healthcare; that he is a consultant for: DEY L.P., Genentech, IVAX Research Inc., MediciNova Inc., Novartis Pharmaceuticals Corporation, Sanofi-Aventis, Teva Specialty Pharmaceuticals, Verus; that he has received honoraria from: AstraZeneca, Genentech, Sanofi-Aventis, Sepracor and Verus; that he is involved with speakers’ bureaux for: AstraZeneca, LP DEY, L.P., Genentech, IVAX Research Inc., Novartis Pharmaceuticals Corporation, Sanofi-Aventis, Sepracor, Verus and that he has received current or previous year grant/research support from: ALK-Abelló, Allergy Therapeutics, Altana Pharma, Amgen, Amphastar Pharmaceuticals Inc., Apieron Biosystems, Apotex, AstraZeneca, Boehringer Ingelheim, Capnia, Centocor Inc., Critical Therapeutics Inc., Curalogic A/S, DEY L.P., Dynavax Technologies Corporation, Genentech, GlaxoSmithKline, Johnson & Johnson, MAP Pharmaceuticals Inc., Meda Pharmaceuticals Inc. (MedPointe), MediciNova Inc., MedImmune Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Perrigo Pharmaceuticals, Renovo Ltd., Salix Pharmaceuticals, Inc., Sanofi-Aventis, Schering-Plough, SkyePharma AG, Wyeth.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she has no relevant financial relationships. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors thank Sarah Filcek of ACUMED for help in preparing the manuscript (this support was funded by Novartis). The authors also thank the patients and staff at participating centers involved, and gratefully acknowledge their co-investigators and fellow participants in the study: Dr Harold B. Kaiser (Clinical Research Institute, Minneapolis MN); Dr David S. Pearlman (Colorado Allergy and Asthma Centers, PC, Denver CO); Dr S. David Miller (Northeast Medical Research Associates, Inc, North Dartmouth, MA).