Original article Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study Inhaled b 2 -agonists have an important role in the management of asthma-related symptoms (1). Currently available agents can be broadly divided into those with a short duration of bronchodilator action (2–4 h, e.g. albuterol) and the longer-acting (12 h) agents formoterol, which is also fast-acting, and salmeterol. Asthma management guidelines (1) recommend that the latter are used as controller agents in conjunction with anti-inflammatory therapy, typically inhaled corticoster- oids. In patients who require additional controller treat- ment in addition to a moderate dose of inhaled corticosteroids, such a regimen has been shown to offer better asthma control compared with the alternative step- up strategy of increasing the dose of inhaled corticoste- roid (2, 3). With chronic diseases such as asthma, patient adher- ence to medication plans is a major obstacle to successful management (4). One factor contributing to poor adher- ence is a complicated or multiple treatment regimen, and simplified dosing regimens are known to improve com- pliance (4, 5). To this end, a logical progression in the development of new asthma therapies is to extend the duration of action of existing classes of agents, as illustrated by inhaled corticosteroids that can be taken once daily such as mometasone or budesonide (6, 7). Similar research efforts are being made with the b 2 -agonist class of bronchodilators. Background: Indacaterol is a novel, once-daily b 2 -agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation. Objective: A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol. Methods: A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 lg via multi-dose dry-powder inhaler (MDDPI; Certihaler TM ), indacaterol 400 lg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored. Results: All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV 1 ) from 22 to 24 h postdose (P £ 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 lg via MDDPI and 400 lg via SDDPI, respectively. All doses increased mean FEV 1 (P < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders. Conclusion: Once-daily dosing with indacaterol provided sustained 24-h bron- chodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 lg appears the optimum dose, offering the best efficacy/safety balance. C. LaForce 1 , M. Alexander 2 , R. Deckelmann 3 , L. M. Fabbri 4 , Z. Aisanov 5 , R. Cameron 6 , R. Owen 6 , M. Higgins 6 1 Department of Pediatrics, University of North Carolina School of Medicine, North Carolina Clinical Research, Raleigh, NC, USA; 2 McMaster University Faculty of Health Sciences, Niagara Clinical Research, Niagara Falls, Canada; 3 Gemeinschaftspraxis mit Dr. Gerald Eckhardt, Internisten, Lungen-und Bronchialheilkunde, Allergologie, Leipzig, Germany; 4 Clinica di Malattie dellÕApparato Respiratorio, Policlinico Università degli Studi di Modena e Reggio Emilia, Via del Pozzo, Modena, Italy; 5 Clinical Physiology Department, Pulmonology Research Institute, Moscow, Russia; 6 Novartis Horsham Research Centre, Horsham, UK Key words: asthma; bronchodilator; efficacy; indacaterol; long-acting b 2 -agonist. Craig LaForce University of North Carolina School of Medicine North Carolina Clinical Research 4301 Lake Boone Trail Raleigh NC 27607 USA Accepted for publication 19 August 2007 Abbreviations: AUC, area under the curve; COPD, chronic obstructive pulmonary disease; FEF 25–75% , forced expiratory flow between 25% and 75% of FVC; FEV 1 AUC 22–24h , FEV 1 stan- dardized (with respect to time) AUC calculated between 22 and 24 h postdose; FEV 1 , forced expiratory volume in 1 s; FVC, forced vital capacity; ITT, intent-to-treat; LLN, lower limit of normal; MDDPI, multi-dose dry-powder inhaler; QTc, corrected QT interval; SDDPI, single-dose dry-powder inhaler; ULN, upper limit of normal. Allergy 2008: 63: 103–111 Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2007.01555.x 103