aclidinium-bromide and Dyspnea

To assess the efficacy and safety of combined aclidinium bromide and long-acting beta. We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.. Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.. We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.. We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV. FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.

Topics: Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Disease Progression; Drug Therapy, Combination; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Tropanes

Bronchodilators are commonly used to manage patients with stable chronic obstructive pulmonary disease (COPD). This meta-analysis assessed the efficacy of aclidinium bromide with respect to clinical events, health-related quality of life and symptom scales, pulmonary function, and safety among patients with stable COPD.. A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library databases was undertaken to identify randomized controlled trials (RCTs) that compared aclidinium with placebo, treatment over at least 12 weeks. Trials were measured using either odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI).. Seven studies, containing 7001 patients, were included in this meta-analysis. Compared with placebo, aclidinium bromide reduced the incidence of exacerbation-related hospitalizations (OR 0.64; 95% CI 0.47 to 0.89) and improved quality of life as measured by a lower total George's Respiratory Questionnaire [SGRQ] score (MD -2.34; 95% CI -3.18 to -1.51) and attenuated dyspnea symptom as assessed by changes in the Transitional Dyspnea Index [TDI] (MD 0.76; 95% CI 0.43 to 1.10). Similar changes were observed with regard to trough FEV1 and FVC and peak FEV1 and FVC. No significant differences were observed with regard to all-cause mortality, COPD exacerbations, non-fatal serious adverse events or cardiac adverse events.. Aclidinium reduced the incidence of exacerbation-related hospitalizations and improved quality of life, COPD symptoms and pulmonary function. In addition, aclidinium did not increase the incidence of non-fatal serious adverse events, cardiac adverse events, or COPD exacerbations and was not associated with increased mortality.

Topics: Cause of Death; Disease Progression; Dyspnea; Forced Expiratory Volume; Hospitalization; Humans; Mortality; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Tropanes; Vital Capacity

The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).. A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.. Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.. Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.. AstraZeneca.

Topics: Bayes Theorem; Bronchodilator Agents; Drug Combinations; Dyspnea; Forced Expiratory Volume; Formoterol Fumarate; Hospitalization; Humans; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Quality of Life; Severity of Illness Index; Tiotropium Bromide; Tropanes

Inhaled bronchodilator therapy is a mainstay of treatment for chronic obstructive pulmonary disease (COPD). Despite the number and types of treatments available, the control of symptoms and exacerbations remains suboptimal, and adherence to, and persistence with, inhaled therapy is generally poor. Results from clinical studies suggest that dual bronchodilator therapy with long-acting muscarinic receptor antagonists (LAMAs) and long-acting β2 adrenergic receptor agonists (LABAs) may provide additional benefit over LAMA or LABA monotherapy without additive effects on safety and tolerability. Several combinations of a LAMA plus a LABA have recently become available in a single inhaler for maintenance therapy for adults with moderate-to-severe COPD, including aclidinium bromide/formoterol fumarate, glycopyrronium/indacaterol and umeclidinium/vilanterol. Here, we review clinical data demonstrating significant improvements in bronchodilation, 24-h symptoms, and health status with aclidinium/formoterol twice daily, and discuss how this treatment can be implemented in clinical practice as part of a patient-focused approach to disease control.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Dyspnea; Formoterol Fumarate; Humans; Lung; Medication Adherence; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tropanes

Long-acting bronchodilators are central for treatment of COPD. This short review provides an overview of studies evaluating the efficacy of aclidinium bromide, a long-acting anticholinergic bronchodilator, for the treatment of COPD. Twice-daily dosing of aclidinium leads to clinically important improvements in forced expiratory volume in 1 second, health status, use of rescue medication, day-time dyspnoea and exercise tolerance. The available studies also suggest an effect on night-time dyspnoea and exacerbation rate in patients with COPD. Aclidinium seems to have potential for a significant role in the future management of COPD.

Topics: Administration, Inhalation; Bronchodilator Agents; Delayed-Action Preparations; Dyspnea; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality of Life; Radiography; Treatment Outcome; Tropanes

Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792).. Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed.. Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8%-9.3%), urinary tract infection (range 4.1%-8.8%) and upper respiratory tract infection (range 2.7%-5.5%). Serious AEs (SAEs) and MACE were low (ranges 6.8%-7.7% and 0.5%-1.5%, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30% versus placebo (p < 0.05).. AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Health Status; Humans; Male; Middle Aged; Muscarinic Antagonists; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Tropanes

Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease. In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators. Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease. The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use. We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies. Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.CHRONIC LUNG DISEASE: 'TRIPLE' THERAPY COULD PROVE BENEFICIAL: A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease. Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD). While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs). Anthony D'Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials. Of these, 1180 were already taking ICSs. The team compared symptoms in the ICS group with those not taking ICSs. The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Dyspnea; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Tropanes

Aclidinium bromide ('aclidinium') is a novel, inhaled long-acting muscarinic antagonist. Therapeutic effects of aclidinium on chronic obstructive pulmonary disease (COPD) have been demonstrated in Caucasian populations in several clinical trials. This was a randomized, double-blind, multi-centre phase-3 clinical trial to evaluate the efficacy and safety of aclidinium in a Korean population.. A total of 263 Korean patients with moderate-to-severe COPD were randomized to receive aclidinium (400 μg, bd) (Genuai) or placebo via a dry-powder inhaler. The primary end point was change in trough forced expiratory volume in one second (FEV1 ) at 12 weeks. Other lung function measurements, COPD exacerbation, health status (St George's Respiratory Questionnaire (SGRQ), dyspnoea (Transition Dyspnea Index (TDI) and safety were assessed throughout the study period.. A significant improvement in trough FEV1 from baseline was shown with aclidinium compared with the placebo (0.126 L, P < 0.0001). Significant improvements were also demonstrated in peak FEV1 (0.190 L, P < 0.0001), SGRQ and TDI. Furthermore, aclidinium significantly reduced the prevalence of exacerbations (aclidinium, 5.4%; placebo, 15.6%, P < 0.05), and the duration of exacerbations was shorter compared with placebo (rate ratio: 0.27; P < 0.05). Aclidinium (400 μg) was well tolerated and the prevalence of adverse events was comparable with the placebo.. Inhaled aclidinium (400 μg) was shown to be safe and efficacious in Korean patients with moderate-to-severe COPD.. NCT01636401 at Clinicaltrials.gov.

Topics: Aged; Bronchodilator Agents; Delayed-Action Preparations; Disease Progression; Double-Blind Method; Dry Powder Inhalers; Dyspnea; Female; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Severity of Illness Index; Tropanes

Standard spyrometric assessment in chronic obstructive pulmonary disease (COPD) only evaluates bronchial obstruction. However, airflow limitation and hyperinflation are the main pathophysiological factors responsible for dyspnoea and reduced exercise tolerance in patients with COPD. This study evaluated the effects of aclidinium bromide 400 μg and glycopyrronium bromide 50 μg on these parameters. Patients with stable severe/very severe COPD were randomized in this double-blind, double-dummy, crossover, Phase IV study. Patients received single doses of each drug on separate days. Primary endpoints were changes in residual volume (RV) and intra-thoracic gas volume (ITGV), assessed by full-body plethysmography. Other endpoints included changes variations in lung ventilation inhomogeneity (Phase III slope of single-breath nitrogen washout test, SBN2), dyspnoea visual analogue scale, and pulmonary specific total airway resistances. Assessments were performed at baseline and 5, 15, 30, 60, and 180 min post-administration. Thirty-seven patients were randomized (31 male; mean age 71 years). Aclidinium and glycopyrronium significantly improved ITGV versus baseline at all-time points (p < 0.05). Significant improvements in RV were observed after 5 min with aclidinium and after 60 min with glycopyrronium. RV improvements were significantly greater with aclidinium than glycopyrronium from 5 to 60 min post-administration (p < 0.05). Both treatments improved dyspnoea versus baseline at all-time points (p < 0.05). Aclidinium significantly improved ventilation inhomogeneity versus baseline at all-time points; no significant changes were observed for glycopyrronium. For the first time two long-acting muscarinic antagonists have been compared in acute conditions with body plethysmography and SBN2 test. We demonstrated that both aclidinium and glycopyrronium significantly reduce hyperinflation and dyspnoea in severe and very severe COPD patients. Aclidinium however promoted a faster reduction in RV and was the only able to reduce lung ventilation inhomogeneity. Trial Registration numbers available on Clinicaltrials.gov: NCT02181023.

Topics: Aged; Aged, 80 and over; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Endpoint Determination; Female; Glycopyrrolate; Humans; Lung; Male; Middle Aged; Plethysmography; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Residual Volume; Respiratory Function Tests; Tropanes

Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.. In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.. At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.. Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD.. ClinicalTrials.gov: NCT01462942.

Topics: Aged; Double-Blind Method; Drug Combinations; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Severity of Illness Index; Tropanes; Vital Capacity

This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity.. In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair(®a) for 3 weeks (2-week washout between treatment periods). The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate. Changes from baseline in intensity of exertional dyspnea (Borg CR10 Scale®) and trough inspiratory capacity were secondary endpoints. Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical activity (assessed by objective accelerometer measurement) parameters. Efficacy endpoints were analyzed using an analysis of covariance model.. In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator forced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s). After 3 weeks, endurance time was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05). At Week 3, aclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference -0.63; p < 0.05) and improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo. Significant improvements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium versus placebo.. These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea, hyperinflation, and physical activity in patients with COPD.. ClinicalTrials.gov identifier: NCT01471171; URL: http://www.clinicaltrials.gov.

Topics: Accelerometry; Aged; Cross-Over Studies; Double-Blind Method; Dyspnea; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Motor Activity; Muscarinic Antagonists; Physical Endurance; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Tropanes

Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.. In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*. Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol). Secondary endpoints were change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety and tolerability were also assessed.. At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001). Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively. All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.. Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo. Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.. Clinicaltrials.gov NCT01437397.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Australia; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dry Powder Inhalers; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Health Status; Humans; Lung; Male; Middle Aged; Muscarinic Antagonists; New Zealand; North America; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Time Factors; Treatment Outcome; Tropanes

This was a 52-week, double-blind, extension study in which COPD patients previously treated with twice-daily (BID) aclidinium bromide 200 μg or 400 μg during a 12-week lead-in study (ACCORD COPD I) continued the same treatment, while patients previously receiving placebo were rerandomized (1:1) to aclidinium 200 μg or 400 μg BID. The primary objective of this study was to evaluate the long-term safety and tolerability of aclidinium treatment. Efficacy outcomes included bronchodilation, health status, and rescue medication use. A total of 467 patients completed the lead-in study and 291 patients consented to participate in the extension. At study end, the percentages of patients who reported a treatment-emergent adverse event (TEAE) were similar for both treatments (200 μg, 77.4%; 400 μg, 73.7%). Incidence of anticholinergic TEAEs was low and similar for both treatments, with dry mouth reported in only 1 patient (400 μg). Cardiac TEAEs were reported by a similarly low percentage of patients (<5% for any event in any group) with no apparent dose dependence. Improvements from baseline in lung function were greatest for patients who received continuous aclidinium treatment and those who were rerandomized from placebo to aclidinium 400 μg; these improvements were generally sustained throughout the study. Health status and overall rescue medication use was improved from baseline for both treatments. The safety profile of twice-daily aclidinium and sustained improvements in lung function and health status throughout the 52-week extension study support its use as a long-term maintenance treatment for patients with COPD. (Clinical trial registration number NCT00970268).

Topics: Acute Coronary Syndrome; Aged; Atrioventricular Block; Bundle-Branch Block; Creatine Kinase; Disease Progression; Double-Blind Method; Drug Eruptions; Dyspnea; Female; gamma-Glutamyltransferase; Headache; Health Status; Heart Failure; Humans; Hypertension; Maintenance Chemotherapy; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Stroke; Tropanes; Xerostomia

This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).. Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6. Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.. Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]). Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (∆ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (∆ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.. Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.

Topics: Aged; Area Under Curve; Bronchodilator Agents; Circadian Rhythm; Cough; Disease Progression; Double-Blind Method; Dry Powder Inhalers; Dyspnea; Female; Forced Expiratory Volume; Headache; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Preference; Pharyngitis; Pulmonary Disease, Chronic Obstructive; Respiratory Sounds; Scopolamine Derivatives; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Tropanes; Xerostomia

The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 μg or 400 μg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV(1)) at week 24. Other end-points included peak FEV(1), health status (St George's Respiratory Questionnaire; SGRQ) and dyspnoea (Transitional Dyspnoea Index; TDI). Overall, 828 patients were randomised. At week 24, significant improvements from baseline were observed with aclidinium 200 μg and 400 μg versus placebo for trough FEV(1) (99 and 128 mL; both p<0.0001) and peak FEV(1) (185 and 209 mL; both p<0.0001). Peak FEV(1) improvements on day 1 were comparable with week 24. Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score (-3.8 and -4.6 units; p<0.001 and p<0.0001) and TDI focal score (0.6 and 1.0 units; p<0.05 and p<0.001) at week 24. With both aclidinium doses, the incidence of anticholinergic adverse events was low, and similar to placebo. Twice-daily aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyspnea; Female; Forced Expiratory Volume; Health Status; Humans; Male; Metered Dose Inhalers; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome; Tropanes

The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).. In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.. At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p<0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p<0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.. Aclidinium is effective and well tolerated in patients with moderate to severe COPD.. ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Dry Powder Inhalers; Dyspnea; Europe; Female; Forced Expiratory Volume; Health Status; Humans; Logistic Models; Lung; Male; Middle Aged; Muscarinic Antagonists; North America; Pulmonary Disease, Chronic Obstructive; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Tropanes

Aclidinium, an inhaled, long-acting antimuscarinic agent, has been developed as a twice-daily maintenance treatment for chronic obstructive pulmonary disease (COPD). Treatment with the approved dosage of aclidinium (400 μg twice daily) statistically significantly improved bronchodilation, disease-specific health status, dyspnoea, night-time COPD symptoms and use of rescue medication compared with placebo in pivotal studies of 12 (ACCORD COPD I) or 24 (ATTAIN) weeks duration in patients with moderate to severe COPD. The improvements in bronchodilation, health status and dyspnoea were clinically meaningful compared with placebo after 24 weeks of treatment in ATTAIN; generally similar results were seen after 12 weeks of treatment in both trials. Aclidinium also statistically significantly reduced the incidence of COPD exacerbations compared with placebo in these studies (albeit neither trial was designed to assess exacerbation frequency). Inhaled aclidinium has a low systemic bioavailability; the approved dosage was generally well tolerated in clinical trials of up to 52 weeks duration. Aclidinium had an adverse event profile that was similar to that of placebo and characterized by low incidences of major adverse cardiovascular events and potential anticholinergic adverse events.

Topics: Biological Availability; Bronchodilator Agents; Dyspnea; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Tropanes