Safety Of Indacaterol Research Articles

Efficacy and Safety of Inhaled Indacaterol and Tiotropium in Patients of Chronic Obstructive Pulmonary Disease

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. Indacaterol is a new once daily inhaled bronchodilator, recently approved for the treatment of COPD. Once daily dosing is an important step to improve the adherence and compliance of the patients. Methods: Efficacy and Safety of Indacaterol and Tiotropium in Patients of COPD with Stage-2 and Stage-3 GOLD criteria were compared. Total 119 patients were divided into Indacaterol group and Tiotropium group receiving 150 mcg daily of Indacaterol and 18 mcg daily of Tiotropium in each group respectively. Efficacy treatment was determined by assessment of Pulmonary function test (PFT), Symptom score and SGRQ (St. George’s Respiratory Questionnaires) score at day zero (before therapeutic intervention) and at two weeks of interval till 24 weeks. Results: The treatment with inhaled indacaterol 150 mcg once daily and inhaled tiotropium 18 mcg once daily improved spirometric variable, FEV1, decrease in mean Symptoms score and in mean SGRQ in Grade-2 and Grade-3 COPD patients. Conclusion: Indacaterol (150 mcg/day) is non-inferior to tiotropium (18 mcg /day) in efficacy and safety profile of Grade-2 and Grade-3 patients with COPD.

The safety of indacaterol for the treatment of COPD

ABSTRACTIntroduction: Bronchodilators, namely long-acting inhaled β2-agonists and long-acting muscarinic antagonists, are the first-line medications for chronic obstructive pulmonary disease (COPD). The safety of these medicines is of great concern since COPD patients usually have other co-morbidities such as cardio- and cerebrovascular diseases.Areas covered: In this review we present information about the safety and the use of indacaterol in COPD. Indacaterol is the first once-daily, long-acting inhaled β2-agonist approved for COPD. We provide data about its mechanism of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present the available literature data focused on the the safety of indacaterol. Data from post-marketing studies are presented and also data from comparative reviews and meta-analysis.Expert opinion: Indacaterol’s safety is very favorable since in controlled trials it was similar to placebo. Nevertheless, physicians must be alerted to use indacaterol only according to its approved indications They must be aware of the possible adverse events since side effects may appear when the medicine is used for a prolonged period of time.

Pharmacokinetics and safety of indacaterol and glycopyrronium (IND/GLY) following repeated once daily inhalation from a fixed-dose combination in healthy Chinese subjects .

Indacaterol/glycopyrronium (IND/GLY) is a once-daily fixed-dose combination of two long-acting bronchodilators: indacaterol 110µg (long-acting β₂-adrenergic agonist, LABA) and glycopyrronium 50µg (long-acting muscarinic antagonist, LAMA). This study assessed the pharmacokinetics of IND/GLY 110/50 µg following multiple once-daily inhaled administrations in healthy Chinese subjects. This was a single-centre, open-label, multiple-dose study of inhaled IND/GLY delivered via the Breezhaler^® device. Pharmacokinetic samples were collected on day 1 after first dose, on days 5, 7, 10, and 12 (predose (trough)) and on day 14 (steady state) after last dose for pharmacokinetic analysis using non-compartmental analysis. Both IND and GLY were absorbed rapidly after inhalation of IND/GLY (t_max: IND, 15 minutes; GLY, 5 minutes). Accumulation through systemic exposure of both IND and GLY from day 1 to day 14 was observed (mean accumulation ratio (R_acc) of AUC_0-24h (day 14/day 1): IND, 3.02; GLY 2.94; estimated accumulation ratio of C_max: IND 1.56; GLY 1.33). Mean effective half-life (t_1/2,acc) was 41.3h and 40.0h for IND and GLY, respectively. Pharmacokinetic steady states were reached after 12 and 10 days of daily dosing for IND and GLY, respectively. There was one mild adverse event (AE) not related to the study drug. No discontinuations due to treatment related AEs/SAEs (adverse event/serious adverse event) were reported. In healthy Chinese subjects, multiple once-daily inhaled doses of IND/GLY 110/50 µg were rapidly absorbed and were safe and well tolerated. The comparison of systemic exposure data following inhalation of IND/GLY 110/50 µg in Chinese vs. the non-Chinese populations did not indicate any clinically relevant differences across ethnicities. .

Combination therapy with indacaterol and glycopyrronium bromide in the management of COPD: an update on the evidence for efficacy and safety.

The international guidelines on chronic obstructive pulmonary disease (COPD) recommend inhaled bronchodilators for maintenance treatment of the disease. These drugs include β2-agonists and muscarinic antagonists, which are both available as short-acting agents (to be used as needed for dyspnea) and long-acting agents. To the latter belong salmeterol and formoterol (long-acting β2-agonists) and indacaterol, vilanterol and olodaterol (very long-acting β2-agonist) as β2-agonists, and tiotropium, aclidinium and glycopyrronium bromide as long-acting muscarinic antagonists. The efficacy and safety of indacaterol and glycopyrronium as monotherapies has been demonstrated in several controlled trials. However, in some patients with moderate-to-severe COPD, symptoms are poorly controlled by bronchodilator monotherapy; in these cases the addition of a second bronchodilator from a different pharmacological class may be beneficial. Here we review the evidence from published randomized trials concerning the efficacy and safety of the once-daily fixed-dose dual bronchodilator combining indacaterol and glycopyrronium.

New developments in the management of COPD: clinical utility of indacaterol 75 µg

Chronic obstructive pulmonary disease (COPD) is a global health challenge and a major cause of mortality worldwide. Bronchodilators, particularly long-acting β2-agonists and long-acting antimuscarinic agents, used singly or in combination, aim to improve lung function, reduce symptoms, prevent exacerbations, and enhance quality of life of COPD patients. Indacaterol is a novel, inhaled, long-acting β2-agonist, with rapid onset of action and once-daily dosing providing 24-hour bronchodilation. Currently, the recommended dose differs between Europe (150 μg; maximum 300 μg) and USA (75 μg), the latter is lower than that assessed in the majority of the conducted studies. This review summarises published evidence regarding the efficacy, tolerability, and safety of indacaterol at a dose of 75 μg. Indacaterol 75 μg was found to be superior than placebo regarding lung function, dyspnea, health status, use of rescue medication, and rate of exacerbations. Furthermore, indacaterol 75 μg was well tolerated, while the most frequent adverse effect was deterioration of COPD occurring at a frequency similar to placebo, without major cardiovascular adverse effects. In conclusion, indacaterol 75 μg, administered once daily, is efficacious and has an excellent tolerability and safety profile, and is therefore a valid alternative in the treatment of COPD patients.

Efficacy and Safety of Indacaterol and Glycopyrronium Bromide in Patients with COPD and Heart Failure

Background: Some studies suggested that analysis of gene expression in myocardial biopsy promised to improve the differential diagnosis of heart failure. On the other hand, higher serum inflammatory markers are known to predict worse prognosis in heart failure without infectious complication. Objective: We examined whether gene expression of inflammatory markers in myocardial biopsy predicted one subgroup of patients with progressive heart disease, indicative of ongoing immune activation. Method: We examined gene expression of inflammatory markersleukocyte markers, inflammatory cytokine and chemokineby quantitative RT-PCR in heart samples from patients admitted to our hospital due to heart failurecardiac biopsy, 55; autopsy, 5. Result: Gene expression of several inflammatory markers was detectable from a small piece of cardiac biopsy. Expression levels of inflammatory markers in samples of myocarditis were higher than those of non-myocarditis. But expression levels of inflammatory markers in some samples of non-myocarditis, progressive heart diseases like fabry disease and mitochondrial cardiomyopathy, were the same as those of myocarditis. Conclusion: High expression of leukocyte marker, inflammatory cytokines and chemokine may predict progressive heart disease, abeit infiltrating immunocompetent cells are not detected histopathologically.

Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study

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. 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 μg) or tiotropium (18 μg) 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. 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). 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 offer evidence consistent with current guidelines. Novartis Pharma AG.

Indacaterol for chronic obstructive pulmonary disease: systematic review and meta-analysis.

BackgroundInhaled bronchodilators are the first-line therapy for COPD. Indacaterol is a novel addition to existing long-acting bronchodilators.ObjectivesSystematic review of randomized controlled trials (RCT) on efficacy and safety of indacaterol as compared: 1) with placebo at different dosages, 2) with existing bronchodilators; (3) as add-on treatment to tiotropium.MethodsWe searched 13 electronic databases, including MEDLINE, EMBASE and CENTRAL, and contacted the manufacturer for unpublished data. Primary outcome was mean FEV1 change at 12th week, secondary outcomes included changes in SGRQ, TDI and BODE index at 6 months, exacerbation at 1 year, and worsening of symptoms.ResultsTwelve eligible RCTs of moderate risk of bias included data from 10,977 patients. Compared to placebo, indacaterol improved FEV1 by a weighted mean difference (WMD) of 0.16 L (95%CI: 0.15, 0.18 L, p<0.001), homogeneously above the minimally important difference of 0.10 L. It offered clinically relevant improvement in all secondary outcomes except exacerbation. Magnitude of benefit did not differ significantly by dosage, but one treatment related death was reported at 300 ug. Efficacy of Indacaterol was similar to formoterol and salmeterol (FEV1 WMD = 0.04L, 95%CI: 0.01L, 0.07 L, p = 0.02); and tiotropium (FEV1 WMD = 0.01L, 95%CI: −0.01, 0.03L, p = 0.61). The use of indacaterol on top of tiotropium yielded additional improvement on FEV1 (WMD = 0.07 L, 95%CI: 0.05L, 0.10 L, p<0.001).ConclusionIndacaterol is safe and beneficial for patients with COPD at dosage ≤150 ug. It may serve as a good alternative to existing bronchodilators, or as an add-on to tiotropium for unresponsive patients. Use of higher dosage requires further justification.

Efficacy and safety of indacaterol and tiotropium in COPD patients according to dyspnoea severity

BackgroundGuidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms. MethodsA post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 μg) and open-label tiotropium (18 μg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = ‘less dyspnoea’; scores ≥2 = ‘more dyspnoea’). Outcomes were assessed after 26 weeks. ResultsThe analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose (‘trough’) forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores at week 26 and reduced the risk of COPD exacerbations vs placebo; and open-label tiotropium improved trough FEV1 and TDI total score vs placebo at week 26. In patients with more dyspnoea: indacaterol (both doses) improved trough FEV1, TDI and SGRQ total scores at week 26; indacaterol 300 μg was the only treatment to improve the TDI total score by more than the minimum clinically important difference (≥1 point) vs placebo; and open-label tiotropium improved trough FEV1, TDI total score at week 26 and decreased the risk of COPD exacerbations vs placebo. In both subgroups, all treatments were well tolerated. ConclusionsIn patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 μg may be a useful treatment option for patients with COPD who experience more severe breathlessness.

Comparison of Indacaterol With Tiotropium or Twice-Daily Long-Acting β-Agonists for Stable COPD: A Systematic Review

Bronchodilators are central to the symptomatic management of patients with COPD.Previous data have shown that inhaled indacaterol improved numerous clinical outcomes over placebo. This systematic review explored the efficacy and safety of indacaterol in comparison with tiotropium or bid long-acting β 2 -agonists (TD-LABAs) for treatment of moderate to severe COPD. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. Five trials (5,920 participants) were included. Compared with tiotropium, indacaterol showed statistically and clinically significant reductions in the use of rescue medication and dyspnea(43% greater likelihood of achieving a minimal clinically important difference [MCID] in the transitional dyspnea index [TDI]; number needed to treat for benefit [NNTB] 5 10). Additionally,the MCID in health status was more likely to be achieved with indacaterol than with tiotropium (OR = 1.43; 95% CI, 1.22–1.68; P = .00001; [NNTB ]= 10). Trough FEV 1 was significantly higher at the end of treatment with indacaterol than with TD-LABAs (80 mL, P = .00001). Similarly, indacaterol signifi cantly improved dyspnea (61% greater likelihood of achieving an MCID in TDI, P = .008) and health status (21% greater likelihood of achieving an MCID in St. George’s Respiratory Questionnaire, P 5 .04) than TD-LABA. Indacaterol showed similar levels of safety and tolerability to both comparators. Available evidence suggests that indacaterol may prove useful as an alternative to tiotropium or TD-LABA due to its effects on health status, dyspnea, and pulmonary function.

Indacaterol: a new long-acting β2-agonist in the management of chronic obstructive pulmonary disease

Introduction: Bronchodilators represent the mainstay of symptomatic treatment for chronic obstructive pulmonary disease (COPD). The principal bronchodilator agents are β2-agonists, anticholinergics and methylxanthines, used singly or in combination. Indacaterol is a novel long-acting β2-agonist for maintenance bronchodilator treatment of airflow obstruction in patients with COPD, approved in December 2009 by the European Medicines Association, and recently by the US Food and Drug Administration. It is administered once daily and is delivered by means of a single-dose dry powder inhaler (SDDPI). In Europe, the recommended dose is 150 μg and the maximum dose is 300 μg, while in the US the recommended dose is 75 μg. Indacaterol shows evidence of a rapid onset of bronchodilation, and its bronchodilatory duration is sustained.Areas covered: Numerous clinical studies have assessed the therapeutic effects of indacaterol in various physiologic parameters, as well as symptoms, disease progression, exacerbation rates, quality of life, safety and tolerability. This review summarises published evidence regarding the efficacy, tolerability and safety of indacaterol in regard to lung function and symptoms of COPD patients.Expert opinion: Indacaterol, the novel once-daily β2-agonist, has rapid and sustained bronchodilatory effect, showing excellent efficacy, tolerability and safety, as shown by all clinical trials so far.

Safety of indacaterol in the treatment of patients with COPD

PurposePooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).Patients and methodsData were pooled from clinical studies of 3–12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214). Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.ResultsThe commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments. The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo. COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo. Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses. Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol. The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07–0.660], P = 0.008).ConclusionIndacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD.

Safety of indacaterol in the treatment of patients with COPD

Safety of indacaterol in the treatment of patients with COPD

Efficacy of a new once-daily long-acting inhaled β2-agonist indacaterol versus twice-daily formoterol in COPD

BackgroundIndacaterol is a long-acting inhaled β2-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast...

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days). Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 microg) or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV(1)AUC(22-24h)) and safety were assessed for 24 h post-dose in each treatment period. Of the 50 patients randomised (92% male; mean age, 67.2 years), 45 completed the study. Standardised FEV(1)AUC(22-24h) was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 microg, respectively (P < 0.001). The improvement in FEV(1) was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points). All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 microg) provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations.

ONCE-DAILY INDACATEROL PROVIDES SUPERIOR BRONCHODILATION, HEALTH STATUS AND CLINICAL OUTCOMES COMPARED WITH SALMETEROL IN PATIENTS WITH CHRONIC OBSTRUCTIVE COPD: A 26-WEEK PLACEBO-CONTROLLED STUDY

PURPOSE: Indacaterol is a novel once-daily (qd) inhaled long-acting β2-agonist. This double-blind, randomized study investigated efficacy and safety of indacaterol in COPD patients versus placebo and salmeterol.

Efficacy and Safety of Indacaterol, a New 24-hour β 2-Agonist, in Patients with Asthma: A Dose-Ranging Study

Background. Indacaterol is a new once-daily inhaled β2-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 μ g or placebo, once daily, via single-dose dry-powder inhaler. After the fourth washout, patients received 1 day of open-label formoterol 12 μ 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 μ g were superior to placebo (p < 0.05) and similar or greater than formoterol 12 μg 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 μg, respectively (all p < 0.05 vs. placebo). Mean FEV1 for indacaterol doses ≥ 200 μg 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.

Indacaterol provides sustained 24 h bronchodilation on once‐daily dosing in asthma: a 7‐day dose‐ranging study

Indacaterol is a novel, once-daily beta(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. A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol. 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 microg via multi-dose dry-powder inhaler (MDDPI; Certihaler), indacaterol 400 microg 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. 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 <or= 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 microg via MDDPI and 400 microg 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. Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 microg appears the optimum dose, offering the best efficacy/safety balance.

Efficacy and safety of single therapeutic and supratherapeutic doses of indacaterol versus salmeterol and salbutamol in patients with asthma

ABSTRACTObjective: This study compared the bronchodilator efficacy and safety of indacaterol with placebo, salbutamol and salmeterol, in patients with persistent asthma, at single therapeutic and supratherapeutic doses.Research design and methods: This was a randomised, open-label crossover study in adult subjects with asthma (forced expiratory volume in 1 second [FEV1] ≥ 60% predicted). In part A, patients (n = 20) received single doses of indacaterol 200 µg, salbutamol 200 µg, salmeterol 50 µg and placebo. In part B, patients (n = 19) received single doses of indacaterol 1000 µg, salbutamol 1000 µg, salmeterol 250 µg and placebo.Main outcomes measures; Results: For the primary endpoint, FEV1 area under the effect curve during 0–24 h, indacaterol 200 µg was statistically superior to placebo and salbutamol. Indacaterol 200 µg FEV1 was higher than placebo (5 min to 24 h), salbutamol 200 µg (4–24 h), and salmeterol 50 µg (5 and 15 min and 22 and 24 h). Few adverse events were reported; all were mild or moderate in severity. Initial changes were observed in glucose, potassium, heart rate and QTc interval, but all values remained within normal ranges. Values matched placebo levels after a shorter time for indacaterol 1000 µg than for salmeterol 250 µg.Conclusions: In this single-dose, open-label study, indacaterol 200 µg provided effective 24‐h bronchodilation, with a longer duration than salmeterol 50 µg and a good overall safety profile. The sustained bronchodilation of indacaterol 1000 µg was not associated with sustained systemic adverse effects.

Safety, tolerability and efficacy of indacaterol, a novel once-daily β2-agonist, in patients with COPD: A 28-day randomised, placebo controlled clinical trial

In patients with chronic obstructive pulmonary disease (COPD) classified as moderate onwards, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend regular treatment with one or more long-acting bronchodilators, such as β 2-agonists or anticholinergics. In contrast to currently available long-acting β 2-agonists, which have a duration of action of 12 h, indacaterol has demonstrated effective 24-h bronchodilation on once-daily dosing. A double-blind, randomised, placebo-controlled study was conducted to compare the safety, tolerability and efficacy of indacaterol with that of placebo, over a 28-day period, in patients with moderate COPD (as defined by GOLD 2001 criteria; equivalent to moderate-to-severe COPD in the GOLD 2005 criteria). Patients were randomised 2:2:1 to receive indacaterol 400 μg or 800 μg or placebo once-daily (between 07:00 and 11:00 h) via a single-dose dry-powder inhaler for 28 days. Assessments included monitoring of adverse events (AEs), blood chemistry (including serum potassium and blood glucose), vital signs (blood pressure and heart rate), electrocardiograms and spirometry. One hundred and sixty-three patients were randomised, with 155 (95%) completing the study. There were no statistically significant differences between treatment groups in the overall incidence of AEs, with AEs reported by 35%, 51% and 25% of patients in the indacaterol 400 μg, 800 μg and placebo groups, respectively. The majority of AEs were mild or moderate in severity, and there were no study-drug related serious AEs. There were no statistically significant differences between indacaterol groups and placebo in mean pulse rate and QTc interval, and isolated statistically significant ( p<0.05) treatment-placebo differences in mean blood pressure, blood glucose and serum potassium. There was a statistically significant improvement in FEV 1 vs placebo at all post-baseline timepoints for both indacaterol treatment groups; 30 min post-dose, adjusted mean±SE FEV 1 indacaterol-placebo differences were: Day 1, 220±36 ml and 210±36 ml; Day 14, 320±50 ml and 270±50 ml; Day 28, 260±61 ml and 200±61 ml for 400 and 800 μg, respectively (all p<0.01 vs placebo). Bronchodilation was still apparent after 24 h, with pre-dose (i.e. trough) adjusted mean±SE FEV 1 indacaterol-placebo differences of: Day 14, 230±44 ml and 210±44 ml; Day 28, 220±49 ml and 210±49 ml for indacaterol 400 and 800 μg, respectively (all p<0.0001 vs placebo). Once-daily indacaterol was well tolerated at doses up to 800 μg with a good overall safety profile. There was no statistical difference at any dose between the safety of indacaterol and placebo. Furthermore, this study supports the previously demonstrated 24-h bronchodilator efficacy of indacaterol.