Indacaterol In Patients Research Articles

Efficacy and safety of indacaterol in patients with chronic obstructive pulmonary disease aged over 65 years: A pooled analysis

BackgroundAlthough the prevalence of chronic obstructive pulmonary disease (COPD) increases with age, no specific therapeutic approaches are available till date for the elderly population. AimTo assess the efficacy and safety of once-daily indacaterol 150 and 300 μg in elderly patients with moderate to severe COPD. MethodsData were pooled from 11 randomized, double-blind, placebo- and active-controlled studies (8445 patients with COPD). The patient population was stratified into age groups: young (≥40–<65 years; 52.3%), elderly (≥65–<75 years; 36.4%), and very elderly (≥75 years; 11.4%). The efficacy outcomes included improvements in trough forced expiratory volume in 1 s (FEV1), transition dyspnea index (TDI), and health status (St. George's Respiratory Questionnaire [SGRQ]); safety was also assessed at 12 weeks. ResultsAt Week 12, the mean improvement in FEV1 with indacaterol 150 μg versus placebo was comparable in the elderly (150 mL), very elderly (160 mL), and young (170 mL) groups (p < 0.001 for all comparisons). Similar improvement in FEV1 was observed with indacaterol 300 μg versus placebo in each group (p < 0.001). This improvement was also significantly higher with indacaterol than formoterol, salmeterol, and tiotropium in all groups (p < 0.01). Both TDI and SGRQ scores significantly improved with indacaterol versus placebo across age groups (p < 0.001) and were significantly higher than that for tiotropium (p < 0.001). Incidences of adverse events among indacaterol- or placebo-treated patients were similar, regardless of the age group. ConclusionsThis pooled analysis suggests that the efficacy and safety of indacaterol treatment is similar between elderly and younger patients with COPD.

Immediate salbutamol responsiveness does not predict long-term benefits of indacaterol in patients with chronic obstructive pulmonary disease

BackgroundThe purpose of this study was to evaluate the correlation between immediate responsiveness with the short-acting β2-agonist salbutamol and effects of treatment with the ultra-long-acting β2-agonist indacaterol in patients with chronic obstructive pulmonary disease (COPD).MethodsThe REVERBREZ study was a phase IV, multicentre, open-label study in which patients with moderate-to-severe COPD received indacaterol 150 μg once-daily for 5 months. The primary endpoint was the correlation between immediate response of forced expiratory volume in 1 s (FEV1) post-inhalation of salbutamol (400 μg) at study entry and the change from baseline in trough FEV1 after 1 month of indacaterol. Secondary endpoints included dyspnoea measured by the modified Medical Research Council (mMRC) grade and health-related quality of life measured by the clinical COPD questionnaire (CCQ).ResultsOf the 602 patients enrolled from 177 centres in France, 543 patients received at least one indacaterol dose, 512 patients completed 1 month of indacaterol treatment (primary endpoint), and 400 patients completed 5 months of treatment. At study entry, mean FEV1 values before and after salbutamol inhalation were 1.54 ± 0.50 L and 1.65 ± 0.53 L, respectively. Based on the magnitude of an immediate response of FEV1 after salbutamol inhalation at study entry, patients were classified into reversible (Rv, ≥12% and ≥200 mL from pre-salbutamol value; n = 106) and non-reversible (NRv, <12% or <200 mL from pre-salbutamol value; n = 431) groups. After 1 month of indacaterol treatment, mean absolute and relative difference in trough FEV1 were 100 mL and 9%, respectively. No significant correlation was found between the immediate FEV1 response to salbutamol at study entry and change from baseline in trough FEV1 after 1 month of indacaterol treatment (correlation coefficient = 0.056 [95% CI;−0.032, 0.144] for absolute response and 0.028 [95% CI;−0.06, 0.116] for relative response). At all subsequent visits, mMRC and CCQ scores, and FEV1 improved from baseline with no significant difference between the Rv and NRv groups.ConclusionsImmediate FEV1 response to salbutamol did not predict the long-term benefits observed with indacaterol treatment in patients with COPD. Patients considered reversible or non-reversible to salbutamol showed comparable improvements in lung function, dyspnoea and health-related quality of life.Trial registrationClinicalTrials.gov: NCT01272362. Date: January 5, 2011

Safety Profile of Glycopyrronium Compared With Once-Daily Indacaterol in Patients With COPD With Moderate-to-Severe Airflow Limitation: The GEM3 Study

Safety Profile of Glycopyrronium Compared With Once-Daily Indacaterol in Patients With COPD With Moderate-to-Severe Airflow Limitation: The GEM3 Study

The impact of treatment with indacaterol in patients with COPD: A post-hoc analysis according to GOLD 2011 categories A to D

BackgroundIndacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). We report on the effectiveness of indacaterol and other bronchodilators compared with placebo in patients across the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 categories A to D. MethodsA post-hoc, subgroup pooled analysis of 6-month efficacy data from three randomized, placebo-controlled, parallel-group studies involving 3862 patients was performed across GOLD 2011 categories A to D, according to baseline forced expiratory volume in 1 s (FEV1) % predicted, modified Medical Research Council (mMRC) dyspnea scale, and exacerbation history in the 12 months prior to entry. Efficacy of once-daily indacaterol 150 and 300 μg, open-label tiotropium 18 μg, twice-daily salmeterol 50 μg, and formoterol 12 μg was compared with placebo. End points analysed were trough FEV1, transition dyspnea index (TDI), and St George's Respiratory Questionnaire (SGRQ) total score, all at Week 26, and mean rescue medication use over 26 weeks. ResultsIndacaterol 150 and 300 μg significantly improved FEV1, compared with placebo across all GOLD groups. Indacaterol 150 and 300 μg also significantly improved TDI, SGRQ total score, and mean rescue medication use compared with placebo across most GOLD subgroups. ConclusionsTreatment selection according to patient's symptoms as well as lung function is an important consideration in maintenance treatment of COPD. Indacaterol 150 and 300 μg effectively improved lung function and symptoms in patients across all GOLD 2011 categories.

The impact of treatment with indacaterol in patients with COPD: A post-hoc analysis according to GOLD 2011 categories A to D

The impact of treatment with indacaterol in patients with COPD: A post-hoc analysis according to GOLD 2011 categories A to D

The safety of long-acting β2-agonists in the treatment of stable chronic obstructive pulmonary disease.

BackgroundInhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD). Both the twice-daily long-acting β2-adrenoceptor agonists (LABAs) salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD. This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths.MethodsWe searched PubMed for placebo-controlled studies evaluating long-term (≥24 weeks) use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012. We summarized data relating to exacerbations and adverse events, particularly events related to COPD.ResultsFrom 20 studies examined (8774 LABA-treated patients), there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths. Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo. Incidences of COPD-related adverse events were similar for active and placebo treatments. The incidence of adverse events typically associated with the β2-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients), and there were no reports of increased incidence of cardiac arrhythmias. The systemic effects of β2-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor.ConclusionCurrent evidence from clinical studies of the safety and tolerability profile of LABAs supports their long-term use in COPD.

Comment on the report “Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease”

Comment on the report “Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease”

Limitations of model based dose selection for indacaterol in patients with chronic obstructive pulmonary disease

Indacaterol is a long-acting β-agonist (LABA) approved by FDA in 2011 at a dose of 75 μg once daily for the treatment of chronic obstructive pulmonary disease (COPD). During the review process for indacaterol approval, data were reanalyzed by FDA to evaluate the validity of the model based conclusions regarding dose selection. The same dose response model applied by the sponsor was used to analyze a subset of the original data. Model predictions were compared with observed data to evaluate the model. Subgroups were created to visualize the relationship between key model parameters and covariates. The Emax model structure was evaluated for a meta-analysis. Patient-level analyses showed that the model based claim of additional benefit of 150 μg over 75 μg for more severe patients is not supported by the data. Mis-specified covariate model structures for key parameters contributed to this inconsistency. The assumed Emax model structure is not supported by the study-level data and the study-level analysis overestimates the incremental difference between two adjacent doses. Even though model based drug development is highly desirable, thorough model evaluation and justification is necessary to ensure the validity of related decisions.

Response to comment on the report “Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease”

Response to comment on the report “Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease”

Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches.

BackgroundIndacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis.MethodsWe utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates.ResultsThe study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID). Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation.ConclusionsComprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 μg is the minimum effective dose, and that 150 and 300 μg are expected to provide optimal bronchodilation, particularly in patients with severe disease.

An update on the use of indacaterol in patients with COPD

Current guidelines for the management of chronic obstructive pulmonary disease (COPD) establish that bronchodilator medications are central to the symptomatic treatment of the disease. Regular treatment with long-acting bronchodilators is recommended as more effective and convenient than short-acting bronchodilators, because the long-acting agents provide greater bronchodilator efficacy and symptomatic relief, increased tolerance to exercise, and improved rate of exacerbations and quality of life test scores. Dosing regimens requiring less frequent dosing also provide improved treatment compliance. Indacaterol is a novel once-daily ultra-long-acting β(2)-agonist bronchodilator now approved in the European Union for maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD, to be administered as 150 or 300 microg once-daily dose by means of a single-dose dry powder inhaler. This review focuses on providing a clinical practice-oriented synopsis of the data generated from the randomized trials during the clinical development of indacaterol, published as of the time of writing. Indacaterol has been shown to provide effective 24-h bronchodilation and a fast onset of action, with an efficacy at least comparable or superior to current bronchodilator therapy standards and with a favourable safety and tolerability profile within the β(2)-agonist drug class.

Indacaterol once-daily is equally effective dosed in the evening or morning in COPD

Indacaterol is a novel, inhaled, long-acting β(2)-agonist providing 24-h bronchodilation with once-daily (o.d.) dosing in patients with COPD. In this double-blind, incomplete block crossover study, patients with moderate-to-severe COPD were randomised to receive three treatment cycles from: indacaterol 300μg o.d. dosed PM or AM, salmeterol 50μg twice daily or placebo, each for 14 days. Trough FEV(1) was measured 24h after indacaterol, and 12h after salmeterol. Ninety-six patients (mean age: 64 years; post-bronchodilator FEV(1) 57% predicted, FEV(1)/FVC 55%) were randomised; 83 completed. After 14 days, the difference vs. placebo in trough FEV(1) for PM indacaterol was 200mL (p<0.001 [primary analysis]) and for AM indacaterol was 200mL (p<0.001). Compared with salmeterol, trough FEV(1) for PM indacaterol was 110mL higher (p<0.001), and for AM indacaterol was 50mL higher (p=NS). Over 14 days, vs. placebo, both PM and AM indacaterol improved the % of nights with no awakenings (by 11.9 and 8.1 points; p<0.01); the % of days with no daytime symptoms (by 6.7 and 5.5 points; p<0.05); and the % of days able to perform usual activities (by 6.7 and 7.8 points; p<0.05). Indacaterol provided 24-h bronchodilation and improvement in symptoms regardless of whether taken regularly in the morning or evening. ClinicalTrials.gov NCT00615030.

Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

indacaterol is a novel, inhaled once-daily ultra-long-acting β(2)-agonist for the treatment of chronic obstructive pulmonary disease (COPD). this study compared the onset of action of single doses of indacaterol 150 and 300 μg with salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo in moderate-to-severe COPD patients. this was a multicenter, randomized, double-blind, placebo-controlled crossover study. The primary variable was forced expiratory volume in one second (FEV(1)) at five minutes postdose. out of 89 patients randomized (mean age 62 years), 86 completed the study. At five minutes postdose, both indacaterol doses were statistically and clinically superior to placebo (P < 0.001), with treatment-placebo differences in FEV(1) of 100 (95% confidence interval [CI] 70-130) mL and 120 (95% CI 90-150) mL for indacaterol 150 and 300 μg, respectively. FEV(1) at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol (10 and 30 mL for indacaterol 150 and 300 μg, respectively) and significantly higher than for salmeterol-fluticasone (50 mL, P = 0.003; 70 mL, P < 0.001, respectively). Moreover, both indacaterol doses showed significantly higher FEV(1) than placebo (P < 0.001) at all postdose time points. The numbers of patients with an FEV(1) increase of at least 12% and 200 mL at five minutes postdose were 16 (18.8%), 24 (27.6%), 20 (23.3%), 8 (9.1%), and 3 (3.4%) for indacaterol 150 and 300 μg, salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo, respectively. single doses of indacaterol 150 and 300 μg demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol-fluticasone.

Bronchodilator efficacy of indacaterol, a novel once-daily β 2-agonist, in patients with persistent asthma

Indacaterol is a novel once-daily inhaled beta2-agonist in development for the treatment of patients with asthma or chronic obstructive pulmonary disease. To investigate the bronchodilator efficacy of indacaterol in patients with persistent asthma. Patients received a randomized sequence of single doses of indacaterol, 400 microg, via single-dose dry powder inhaler (SDDPI); indacaterol, 200 microg, via multidose dry powder inhaler (MDDPI); and placebo. At each visit, the forced expiratory volume in 1 second (FEV1) was recorded at a series of time points during a 24-hour period. Of 33 patients screened, 25 were randomized to treatment. Adjusted mean FEV1 was significantly higher (P < or = .005) for both indacaterol doses vs placebo at most time points. The first time points at which statistically significant treatment differences were observed for indacaterol and placebo in FEV1 were 0.17 L at 5 minutes after dosing for 400 microg of indacaterol (SDDPI) and 0.21 L at 10 minutes for 200 microg of indacaterol (MDDPI) (both P < .001 vs placebo). Differences relative to placebo at the final time point, 24 hours after dosing, were 0.29 L and 0.15 L for indacaterol, 400 microg and 200 microg, respectively (both P < or = .003 vs placebo). Overall, FEV1 was significantly higher for the 400-microg dose compared with the 200-microg dose from 15 minutes to 2 hours after dosing (P < or = .013) and from 5 hours onward (P < or = .022). Indacaterol was associated with good tolerability and safety. Indacaterol demonstrates sustained bronchodilator efficacy throughout the full 24-hour period, with a rapid onset of action and a good overall safety profile.

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.