A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison

SummaryThis dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled β2-agonist, in subjects clinically diagnosed with COPD. Comparative data with tiotropium were collected.In the double-blind, core period of the study, 635 subjects with COPD (prebronchodilator FEV1⩾40% of predicted and ⩾1.0L; FEV1/FVC <70%) were randomized to receive indacaterol 50, 100, 200 or 400μg or placebo via multi-dose dry powder inhaler, or indacaterol 400μg via single-dose dry powder inhaler, once daily for 7 days. After completing double-blind treatment and washout, a subset of subjects from each treatment group entered an open-label extension and received tiotropium 18μg once daily for 8 days. The primary efficacy variable was the trough bronchodilator effect: standardized area under the FEV1 curve between 22 and 24h post-dose (FEV1 AUC22–24h) on Day 1.Clinically relevant improvements versus placebo in FEV1 AUC22–24h were seen for 400 and 200μg doses on Day 1 and all doses on Day 7. All indacaterol doses significantly (P<0.05) increased FEV1 from 5min to 24h post-dose; the 400 and 200μg doses were most effective. All doses were well tolerated. Indacaterol trough FEV1 levels compared favorably with the improvement seen by Day 8 in subjects treated with tiotropium in the open-label extension.The results confirm that indacaterol has a 24-h duration of bronchodilator effect and a fast onset of action in COPD and suggest that indacaterol could be an effective once-daily inhaled β2-agonist bronchodilator. Indacaterol demonstrated a good overall safety and tolerability profile

Tiotropium improves lung function in patients with severe uncontrolled asthma:A randomized controlled trial

Background: Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients. Objective: We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 mu g daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, >= 1.5; postbronchodilator FEV(1), Methods: This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV(1) at the end of each treatment period. Results: Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV(1), 65% of predicted value), 100 completed all periods. Peak FEV(1) was significantly higher with 5 mu g (difference, 139 mL; 95% CI, 96181 mL) and 10 mu g (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P <.0001). There was no significant difference between the active doses. Trough FEV(1) at the end of the dosing interval was higher with tiotropium (5 mg: 86 mL [95% CI, 41-132 mL]; 10 mg: 113 mL [95% CI, 67-159 mL]; both P <.0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 mu g of tiotropium. Conclusion: The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting beta(2)-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma. (J Allergy Clin Immunol 2011;128:308-14.

Effects of short-acting Bronchodilators added to maintenance tiotropium therapy

Background: Combining bronchodilators has been shown to be beneficial in patients with COPD. The additive effects of short-acting bronchodilators added to maintenance tiotropium therapy, however, are unknown. Methods: Following 3 weeks of tiotropium pretreatment, 60 patients with COPD (FEV1 40% of predicted) participated in a randomized, placebo-controlled study to assess add-on bronchodilator effects of ipratropium bromide (40 mu g) or fenoterol (200 jig). Short-acting bronchodilators were added as a single dose 2 h and 8 h after tiotropium dosing. Serial lung function tests were performed over 9 h. Results: The peak FEV1 add-on response within 6 h with fenoterol was significantly greater than with placebo (137 mL) or ipratropium (84 mL); the response with ipratropium was slightly but significantly larger than with placebo (52 mL). One hour after the second dose of the test drugs, a similar order of treatment responses was found. The peak FVC add-on response was significant for fenoterol (249 mL) but not for ipratropium (42 mL). Conclusions: In conclusion, both short-acting bronchodilator classes were effective when added to maintenance treatment with tiotropium. The addition of the beta(2)-adrenergic fenoterol provided greater additional bronchodilatation than the short-acting anticholinergic ipratropium. This is consistent with the expected effects of combining bronchodilators; with different pharmacologic mechanisms. This randomized controlled trial was registered at www.clinicaltrials.gov (NCT00274066)