Contrary to GOLD recommendations, patients at low risk of exacerbation and moderate airflow limitation are frequently prescribed inhaled corticosteroids. 1 Recent data from INSTEAD showed that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC 50/500µg BID to indacaterol 150µg with no efficacy decrease. 2 Exploratory symptom efficacy data are presented here. Methods were published previously. 2 Patients recorded morning/evening daily respiratory symptoms, cough, wheezing, sputum volume and colour, breathlessness, sore throat, cold and fever. This analysis was a prespecified exploratory objective. The percentage of nights with no night-time awakenings, days with no daytime symptoms, and days able to perform usual daily activities were calculated over 12 and 26 wks treatment, as were mean individual diary symptom scores. There were no statistically significant differences between indacaterol and SFC for any variable, illustrated in Table 1. Patients at low risk of exacerbation can be switched from SFC to indacaterol with no deterioration in symptoms or symptoms scores. Vestbo J et al Respir Med 2014;108:729-36 Rossi A et al ERJ 2014;44:1548-56

Introduction Many patients with low risk of COPD exacerbations receive twice-daily (bid) LABA/ICS, salmeterol/fluticasone (SFC), for maintenance treatment. This study evaluated the effect of switching these patients to a once-daily (od) LABA, indacaterol, monotherapy. Methods INSTEAD was a 26-week double-blind, double-dummy study in patients aged ≥40 years, with moderate COPD (post-bronchodilator FEV1 50–80% predicted) and no exacerbations in the past 12 months, who were receiving SFC 50/500 μg bid for ≥3 months prior to study entry. Patients were randomised (1:1) to continue with SFC 50/500 μg or to be switched (with no washout) to indacaterol 150 μg. The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough FEV1 after 12 weeks (non-inferiority margin: 60 mL). Trough FEV1 was also evaluated at 4, 8 and 26 weeks. TDI and SGRQ-C total scores were evaluated at Weeks 12 and 26; the annualised rate of exacerbations and safety were evaluated over 26 weeks. Results A total of581 patients were randomised (indacaterol: 293; SFC: 288); 85.4% completed the study. The primary endpoint was met, with a LSM difference in trough FEV1 between indacaterol and SFC of –9 mL (95% CI: –45 to 26 mL; p = 0·002 for NI). There were no significant differences between treatments in trough FEV1 at any of the other visits (Baseline and Weeks 4, 8 and 26). The TDI and SGRQ-C total scores and their responder rates were similar between two treatments, at both Weeks 12 and 26 (Table 1). During the 26 week treatment period, 79.5% and 74.7% of patients in the indacaterol and SFC groups, respectively, experienced no exacerbations. There was no statistically significant difference between treatments in the rate of all COPD exacerbations per year, with rates of 0.57 vs 0.67, respectively (RR 0.86 [95% CI 0.62, 1.20]; p = 0.367). Adverse events (AEs) and serious AEs were comparable between the treatment arms. Conclusion Indacaterol was non-inferior to SFC in terms of bronchodilation and showed similar efficacy in terms of breathlessness, health status, and exacerbation rate indicating that this group of patients can be switched from SFC to indacaterol 150 µg with no loss in efficacy.

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily. Patients had been receiving SFC 50/500 μg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV 1 ) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45–26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George’s Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss.

Background We compared the efficacy and safety of indacaterol and tiotropium in patients with severe chronic obstructive pulmonary disease (COPD) and a history of at least one moderate to severe exacerbation in the previous 12 months.Methods In this multicentre, randomised, blinded, double-dummy, parallel group study, we enrolled patients aged 40 years or older with severe COPD and at least one exacerbation within the previous year. We used a computer-generated sequence to randomly allocate patients (1:1; stratified by baseline inhaled corticosteroid use, with the balance of treatments maintained at country level) to receive either indacaterol (150 mu g) or tiotropium (18 mu g) once-daily for 52 weeks. Our primary and key secondary objectives were to investigate whether indacaterol was non-inferior to tiotropium for trough forced expiratory volume in 1 s (FEV1) at week 12 (primary endpoint), and for rate of exacerbations at week 52 (secondary endpoint). Analysis populations for the primary and key secondary endpoints were per-protocol sets. The safety set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00845728.Findings Between March 16, 2009, and July 5, 2012, we enrolled and randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium. At week 12, the estimated least squares mean trough FEV1 difference between the groups was -0.011 L (least squares mean with indacaterol [n=1450] 1.134 L [SE 0.008] vs tiotropium [n=1467] 1.145 L [0.008]; one-sided 97.5% CI lower limit -0.026 L; p<0.0001). The lower limit of the 97.5% CI was above the prespecified non-inferiority margin of -0.055 L, suggesting that indacaterol was non-inferior to tiotropium. Indacaterol did not show non-inferiority in terms of annualised exacerbation rates: 0.79 (indacaterol, n=1529) versus 0.61 (tiotropium, n=1543); ratio 1.29 (one-sided 97.5% CI upper limit 1.44). In the safety set, we recorded no between-group difference in the number of patients who had adverse events (indacaterol 1119 [65%] of 1721 patients vs tiotropium 1065 [62%] of 1718 patients) or serious adverse events (indacaterol, 263 [15%] of 1721 patients vs tiotropium, 255 [15%] of 1718 patients). Respiratory disorders, particularly worsening of COPD, were the most common adverse events (COPD: indacaterol, 747 [43%] of 1721 patients and tiotropium, 665 [39%] of 1718 patients) and serious adverse events (COPD: indacaterol, 147 [9%] of 1721 patients and tiotropium, 121 [7%] of 1718 patients).Interpretation Indacaterol and tiotropium provided clinically relevant improvements in lung function with comparable safety profiles. Tiotropium afforded greater protection from exacerbations, although the absolute number of events was small and the difference between treatments is of uncertain clinical importance. The present data off er evidence consistent with current guidelines.

Background. Indacaterol is a new once-daily inhaled 2-agonist in clinical development for asthma as a component of a fixed-dose combination with an inhaled corticosteroid. Objectives. To investigate the efficacy and safety of indacaterol in patients with chronic persistent asthma. Methods. A total of 115 patients were randomized in a double-blind, incomplete-block cross-over design to sequences of four 7-day treatment periods (separated by 7-day washouts) with indacaterol 100, 200, 300, 400, or 600 g or placebo, once daily, via single-dose dry-powder inhaler. After the fourth washout, patients received 1 day of open-label formoterol 12 g twice daily. Forced expiratory volume in 1 second (FEV1) was measured for 24 hours post-dose on days 1 and 7. Results. For standardized (with respect to time) FEV1 area under the curve at 22 to 24 hours (AUC22-24h) on day 1, indacaterol doses 200 g were superior to placebo (p 0.05) and similar or greater than formoterol 12 g twice daily. By day 7, mean differences from placebo in FEV1 standardized AUC22-24h were 0.08, 0.16, 0.15, 0.11, and 0.16 L for indacaterol 100, 200, 300, 400, and 600 g, respectively (all p 0.05 vs. placebo). Mean FEV1 for indacaterol doses 200 g on day 7 was higher than placebo (p 0.05) pre-dose and at all post-dose time points. AEs were generally mild in severity; no serious AEs occurred. No clinically meaningful differences were observed between treatments in any safety assessments. Conclusions. Once-daily indacaterol demonstrated sustained 24-hour bronchodilator efficacy, with similar efficacy on days 1 and 7, and was generally well tolerated.

Background: Indacaterol is a novel, inhaled, once-daily beta(2)-agonist.Objective: To investigate the safety and tolerability of indacaterol at doses of 400 and 800 mu g/d.Methods: Randomized, double-blind, placebo-controlled, parallel-group, multicenter, 28-day study. Patients with persistent asthma (forced expiratory volume in 1 second [FEV1] >= 60% predicted, <= 1,600 mu g of beclomethasone dipropionate or equivalent daily) received indacaterol, 400 mu g (n = 59) or 800 mu g (n = 59), or placebo (n = 26) once daily via a single-dose dry powder inhaler. Safety assessments were performed before and after dosing on days 1, 14, and 28, with particular attention to key beta(2)-agonist safety variables.Results: A total of 144 patients were randomized, with 135 (93.8%) completing the study. Indacaterol was well tolerated: the incidence of adverse events (AEs) was similar between the active and placebo groups, and AEs, when they occurred, were mild or moderate for most (98.2%). There was no dose-response relationship between indacaterol and the incidence of AEs (400 mu g, 40.7%; 800 mu g, 37.3%; and placebo, 38.5%). Few AEs considered as beta(2)-agonist class effects occurred (none leading to withdrawal). Small differences between indacaterol and placebo in mean serum potassium (<=-0.29 mmol/L) and glucose (<= 0.93 mmol/L) levels were occasionally statistically significant (P <.05) but not regarded as clinically meaningful. As expected for a beta(2)-agonist, there was some indication of a trend in QTc prolongation with increasing exposure (maximum mean change, 8.9 milliseconds; P <.05 vs placebo). Significant increases in FEV1 (P <.05) were seen at all postbaseline time points for both indacaterol doses vs placebo, with indacaterol-placebo differences 30 minutes after dosing of 0.21 to 0.25 L and before dosing on days 14 and 28 (approximately 24 hours after the previous dose) of 0.15 to 0.23 L.Conclusion: Indacaterol had a good overall safety profile and was well tolerated at both doses, with predose FEV1 results on days 14 and 28 indicating 24-hour bronchodilator efficacy.

The safety and tolerability of indacaterol, a novel once-daily beta(2)-agonist bronchodilator with a fast onset of action, were assessed in 156 asthma patients in a multicentre, randomized, double-blind, placebo-controlled study. Patients received indacaterol 200, 400 or 600 mu g or placebo once daily for 28 days. Adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, spirometry and physical examinations were monitored. Indacaterol pharmacokinetics were assessed.There was no evidence of dose-retated increases in AE incidence or clinically significant hypokalaemia or hyperglycaemia in indacaterol-treated patients. Mean pulse rate changes were minor in any group, with maximum 1-h post-dose changes from baseline of -3.7, -3.3 and -2.2bpm for indacaterol 200, 400 and 600 mu g, respectively, and -2.9bpm for placebo. Mean QTc interval was similar between groups; change from baseline >60 ms occurred in only two patients. Mean FEV1 increased after the first indacaterol dose; baseline-adjusted pre-dose (trough) values remained >= 166 mL higher than placebo at all subsequent visits, supporting a 24-h bronchodilator effect. Pre-dose (but not post-dose) serum indacaterol concentrations indicated a slight trend for accumulation.Once-daily indacaterol 200-600 mu g has a favourable therapeutic index. It is well tolerated, and is not associated with any adverse cardiac or metabolic effects, while providing effective 24-h bronchodilation. (C) 2007 Elsevier Ltd. All rights reserved.