Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium

Respiratory Research, Oct 2010

Background Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD. Methods In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 μg, indacaterol 300 μg, tiotropium 18 μg and placebo, each once-daily for 14 days. Each treatment period was separated by a 14-day washout. Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators. The primary efficacy variable was trough forced expiratory volume in one second (FEV1) at 24 h post-dose after 14 days. The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variable. Results A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed. Trough FEV1 after 14 days with indacaterol 150 μg and 300 μg was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001). For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 μg, respectively. At 5 min post-dose on Day 1, the mean FEV1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indacaterol 150 and 300 μg, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001). Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 μg and 300 μg, tiotropium and placebo treatments, respectively. Conclusions Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation. Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing. Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended. Trial registration ClinicalTrials.gov: NCT00615459, EudraCT number: 2007-004071-19

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Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium

Vogelmeier et al. Respiratory Research Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium Claus Vogelmeier 3 David Ramos-Barbon 2 Damon Jack 1 Simon Piggott 1 Roger Owen 1 Mark Higgins 1 Benjamin Kramer [email protected] 0 4 INTIME study investigators (INdacaterol TIotropium: Measuring Efficacy) 0 Novartis Pharmaceuticals Inc. , One Health Plaza, East Hanover, NJ 07936- 1080 , USA 1 Novartis Horsham Research Centre , Wimblehurst Road, Horsham, West Sussex RH12 5AB , UK 2 Respiratory Department and Instituto de Investigacion Biomedica de A Coruna (INIBIC), Complexo Hospitalario Universitario A Coruna , 15006, A Coruna , Spain 3 Universitatsklinikum Gieen und Marburg , Standort Marburg, Baldingerstrae, D-35043, Marburg , Germany 4 Novartis Pharmaceuticals Inc. , One Health Plaza, East Hanover, NJ 07936-1080 , USA Background: Indacaterol is a novel, inhaled, once-daily, ultra-long-acting b2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD. Methods: In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 g, indacaterol 300 g, tiotropium 18 g and placebo, each once-daily for 14 days. Each treatment period was separated by a 14-day washout. Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators. The primary efficacy variable was trough forced expiratory volume in one second (FEV1) at 24 h post-dose after 14 days. The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variable. Results: A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed. Trough FEV1 after 14 days with indacaterol 150 g and 300 g was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001). For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 g, respectively. At 5 min post-dose on Day 1, the mean FEV1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indacaterol 150 and 300 g, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001). Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 g and 300 g, tiotropium and placebo treatments, respectively. Conclusions: Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation. Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing. Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended. - Background According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), inhaled bronchodilators, including b2-agonists and anticholinergics, are central to the symptomatic management of chronic obstructive pulmonary disease (COPD) [1]. Currently available inhaled long-acting b2-agonists (LABAs), such as salmeterol and formoterol, provide bronchodilation for approximately 12 h at recommended doses, and hence are administered twice daily [2,3]. Tiotropium, the only currently available long-acting anticholinergic, has a duration of action of 24 h with once-daily dosing, and is effective in the long-term maintenance bronchodilator treatment of COPD [4-6]. Once-daily dosing of tiotropium has been shown to improve a range of clinical outcomes and exacerbations in patients with COPD compared with twice-daily LABAs and the anticholinergic ipratropium four times daily [5,7-9]. However, COPD remains a chronic disabling condition and additional therapeutic options are needed to achieve optimal disease management. Furthermore, patients compliance with treatment could be improved if regimens are simplified by reducing the dosing frequency - especially given that the high incidence of comorbidities means that many patients with COPD require polypharmacy [10]. Indacaterol is a novel, inhaled, once-daily ultra LABA for the treatment of COPD [11]. Indacaterol has shown good overall safety and tolerability in clinical studies of up to 1-year duration with 24-h bronchodilator efficacy on once-daily dosing [12-17]. Two previous clinical trials have compared indacaterol with tiotropium, but due to the unavailability of a matching placebo, tiotropium was administered openlabel [13,15]. The first study was a 7-day placebocontrolled dose ranging study, (...truncated)


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Claus Vogelmeier, David Ramos-Barbon, Damon Jack, Simon Piggott, Roger Owen, Mark Higgins, Benjamin Kramer, . Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium, Respiratory Research, 2010, pp. 135, 11, DOI: 10.1186/1465-9921-11-135