Sustained 24-hour efficacy of once daily indacaterol (300 μg) in patients with chronic obstructive pulmonary disease: A randomized, crossover study
Introduction
Chronic obstructive pulmonary disease (COPD) is a major (and increasing) cause of morbidity and mortality worldwide [1]. The condition is characterized by progressive airflow limitation and air trapping, resulting in hyperinflation. This hyperinflation reduces inspiratory capacity resulting in dyspnea and limitations in exercise capacity [2].
COPD treatment guidelines, including those from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [2], advocate the use of inhaled bronchodilators, including β2-agonists, at all COPD stages to improve expiratory flow and emptying of the lungs, thereby reducing hyperinflation at rest and during exercise [2]. Regular treatment with long-acting bronchodilators in symptomatic COPD patients has been shown to be more effective and convenient than treatment with short-acting bronchodilators [2]. Currently available inhaled long-acting β2-agonists (LABAs), such as salmeterol and formoterol, induce bronchodilation that lasts for approximately 12 h and are therefore administered twice daily [3], [4], [5], [6].
Indacaterol is a novel, inhaled, ultra-LABA [7] for the treatment of COPD. In clinical trials, indacaterol has demonstrated 24-h bronchodilation with once daily dosing, with a good overall safety and tolerability profile [8], [9]. The majority of studies conducted thus far with indacaterol have incorporated relatively few spirometric assessments between 12 and 22 h post-dose. This study was therefore conducted to further characterize the 24-h lung spirometric profile of indacaterol 300 μg once daily in patients with moderate-to-severe COPD by incorporating multiple spirometric assessments across the full 24-h dosing interval.
Section snippets
Methods
This was a Phase III, randomized, multicenter, double-blind, placebo-controlled, crossover study conducted at specialized respiratory care centers in Belgium, Spain, and the US (ClinicalTrials.gov registration no.: NCT00622635) [10]. The study was approved by the institutional review board or the independent ethics committee of each participating study center and was conducted in accordance with the ethical principles embodied in the Declaration of Helsinki (1989) and applicable local
Patient disposition, demographics, and baseline characteristics
This study was conducted at 11 centers in 3 countries (6 in the USA, 3 in Belgium, and 2 in Spain). Out of 101 patients screened, 68 were randomized, and 61 (89.7%) completed the study. The most common reason for premature discontinuation was AE(s) (four patients), followed by withdrawal of consent (two patients) and abnormal test result(s) (one patient). Discontinuations were higher during treatment with salmeterol (n = 4) compared with indacaterol (n = 1) or placebo (n = 2).
The baseline
Discussion
The majority of studies conducted so far with once daily indacaterol have incorporated relatively few spirometric assessments between 12 and 22 h post-dose. This has generally been done to permit patients to rest overnight and avoid the requirement for them to remain in the study center for a full 24-h period. This was the first study to evaluate the spirometric profile of indacaterol 300 μg once daily in patients with COPD across the full 24-h dosing interval. In particular, the time points at
Conclusion
Indacaterol 300 μg once daily produced effective bronchodilation from the first dose, with efficacy compared with placebo that was sustained over 24-h. The efficacy of indacaterol was greater than that of open-label salmeterol administered twice daily. Indacaterol was generally well tolerated with a good overall safety profile. Indacaterol is therefore a useful alternative to the established bronchodilator therapies in patients with moderate-to-severe COPD. The sustained 24-h profile of
Disclosure statement
Amir Iqbal, David Young, Roger Owen, Mark Higgins and Benjamin Kramer are employees of the study sponsor, Novartis. Craig LaForce has received fees for speaking for Novartis. Joseph Aumann and Luis de Teresa Parreño have no actual or potential conflict of interest. All authors contributed to the development of the manuscript, and approved the decision to submit the manuscript for publication.
Funding
This study was funded by Novartis Pharma AG, Basel, Switzerland. The sponsor (represented by AI, DY, RO, MH and BK) was responsible for the design and analysis of the study, and for the writing of the study report. CLF, JA and LdTP were involved in the collection of data.
Acknowledgements
The authors thank the patients who took part and the staff at the participating clinical centers, and express special thanks for the conduct of the study to the principal investigators at the participating centers. The authors acknowledge Lakshmi Kasthurirangan, professional medical writer (Novartis) for assistance in the preparation of this manuscript.
References (31)
- et al.
Chronic obstructive pulmonary disease
Lancet
(2003) - et al.
Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study
Respir Med
(1995) - et al.
Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD
Chest
(2002) - et al.
Safety, tolerability and efficacy of indacaterol, a novel once-daily β2-agonist, in patients with COPD: a 28-day randomised, placebo controlled clinical trial
Pulm Pharmacol Ther
(2007) - et al.
A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison
Respir Med
(2008) - et al.
Safety and tolerability of indacaterol in asthma: a randomized, placebo-controlled 28-day study
Respir Med
(2007) - et al.
Bronchodilator efficacy of indacaterol, a novel once-daily β2-agonist, in patients with persistent asthma
Ann Allergy Asthma Immunol
(2008) - et al.
Efficacy of salmeterol xinofoate in the treatment of COPD
Chest
(1999) - et al.
Tiotropium bromide: a new long-acting bronchodilator for the treatment of chronic obstructive pulmonary disease
Clin Ther
(2005) - et al.
Once-daily indacaterol provides superior bronchodilation, health status and clinical outcomes compared with salmeterol in patients with chronic obstructive disease (COPD): a 26-week placebo-controlled study
Chest
(2009)
Once-daily indacaterol provides effective bronchodilation over 1 year of treatment in patients with chronic obstructive pulmonary disease (COPD)
Chest
Bronchodilator effects of indacaterol and formoterol in patients with COPD
Pulm Pharmacol Ther
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease
Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study
Thorax
An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)
Eur Respir J
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