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Esther Garcia Gil - One of the best experts on this subject based on the ideXlab platform.
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effect of Aclidinium Bromide on major cardiovascular events and exacerbations in high risk patients with chronic obstructive pulmonary disease the ascent copd randomized clinical trial
JAMA, 2019Co-Authors: Robert A Wise, Kenneth R Chapman, Benjamin M Scirica, Deepak L Bhatt, Sami Z Daoud, Colin Reisner, Sofia Zetterstrand, Esther Garcia GilAbstract:Importance There is concern that long-acting muscarinic antagonists increase cardiovascular morbidity or mortality in patients with chronic obstructive pulmonary disease (COPD). Objective To determine the cardiovascular safety (noninferiority) and efficacy (superiority) of Aclidinium Bromide, 400 μg twice daily, in patients with COPD and cardiovascular disease or risk factors. Design, Setting, and Participants Multicenter, randomized, placebo-controlled, double-blind, parallel-design study conducted at 522 sites in North America. A total of 3630 patients with moderate to very severe COPD and either a history of cardiovascular disease or at least 2 atherothrombotic risk factors were randomized; follow-up occurred for up to 3 years until at least 122 major adverse cardiovascular events (MACE) occurred. The first patient was enrolled on October 16, 2013 and the last on August 22, 2016. The final patient completed follow-up on September 21, 2017. Interventions Patients were randomized to receive Aclidinium (n = 1812) or placebo (n = 1818) by dry-powder inhaler, twice daily for up to 3 years. Main Outcomes and Measures The primary safety end point was time to first MACE over up to 3 years (hazard ratio [HR] 1-sided 97.5% CI noninferiority margin = 1.8). The primary efficacy end point was the annual COPD exacerbation rate during the first year of treatment. Secondary outcomes included an expanded MACE definition (time to first MACE or serious cardiovascular event of interest) and annual rate of exacerbations requiring hospitalization. Results Among 3589 patients analyzed (mean age, 67.2 years; 58.7% male), 2537 (70.7%) completed the study. Of these, 69 (3.9%) Aclidinium and 76 (4.2%) placebo patients had a MACE (HR, 0.89; 1-sided 97.5% CI, 0-1.23); the expanded MACE definition included 168 (9.4%) Aclidinium vs 160 (8.9%) placebo patients with events (HR, 1.03; 1-sided 97.5% CI, 0-1.28). Annual moderate to severe exacerbation rates (Aclidinium, 0.44; placebo, 0.57; rate ratio, 0.78; 2-sided 95% CI, 0.68-0.89; P P = .006) decreased significantly with Aclidinium vs placebo. The most common adverse events were pneumonia (Aclidinium, 109 events [6.1%]; placebo, 105 events [5.8%]), urinary tract infection (Aclidinium, 93 events [5.2%]; placebo, 89 events [5.0%]), and upper respiratory tract infection (Aclidinium, 86 events [4.8%]; placebo, 101 events [5.6%]). Conclusions and Relevance Among patients with COPD and increased cardiovascular risk, Aclidinium was noninferior to placebo for risk of MACE over 3 years. The rate of moderate to severe COPD exacerbations was reduced over the first year. Trial Registration ClinicalTrials.gov Identifier:NCT01966107
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long term evaluation of the effects of Aclidinium Bromide on major adverse cardiovascular events and copd exacerbations in patients with moderate to very severe copd rationale and design of the ascent copd study
Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, 2018Co-Authors: Robert A Wise, Kenneth R Chapman, Benjamin M Scirica, David A Schoenfeld, Deepak L Bhatt, Sami Z Daoud, Beatriz Seoane, Colin Reisner, Esther Garcia GilAbstract:Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness characterized by persistent airflow obstruction and exacerbations. Patients typically experience a decline in lung function, increasingly impaired health-related quality of life, and high mortality. Poor lung function and exacerbations are associated with an increased risk of cardiovascular (CV) and cerebrovascular events, and approximately 30% of patients with COPD die from CV‑related disease. Treatment with inhaled long-acting bronchodilators, such as long-acting muscarinic antagonists (LAMAs), is recommended; however, some studies have suggested that LAMAs may increase the risk of CV events. As patients with CV and cerebrovascular conditions are often excluded from clinical trials, an evaluation of the safety of COPD treatments in an at-risk population is vital. Aclidinium Bromide is a LAMA approved for the long-term maintenance treatment of COPD. Methods and Objectives: The Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group Aclidinium Bromide on Long-Term Cardiovascular Safety and COPD Exacerbations in PatieNTs with Moderate to Very Severe COPD (ASCENT COPD) study ({"type":"clinical-trial","attrs":{"text":"NCT01966107","term_id":"NCT01966107"}}NCT01966107) is being conducted at 500 sites in the United States and Canada. The primary objectives are to evaluate the long-term effects of twice-daily Aclidinium Bromide 400 µg on CV safety and exacerbations in patients with moderate to very severe COPD with a history of cerebrovascular, coronary, or peripheral artery disease, or the presence of ≥2 atherothrombotic risk factors. The primary safety and efficacy variables are time to first major adverse CV event (MACE) (on-study analysis) and rate of moderate to severe COPD exacerbations during the first year of treatment (on-treatment analysis), respectively. The study will be terminated after approximately 122 MACE have occurred.
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improvement in 24 hour bronchodilation and symptom control with Aclidinium Bromide versus tiotropium and placebo in symptomatic patients with copd post hoc analysis of a phase iiib study
International Journal of Chronic Obstructive Pulmonary Disease, 2017Co-Authors: Jutta Beier, Ferran Chuecos, Annemarie Kirsten, R M Mroz, Esther Garcia GilAbstract:BACKGROUND A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with Aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo. This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study. METHODS Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ≥10 units) received Aclidinium Bromide 400 μg twice daily (BID), tiotropium 18 μg once daily (QD), or placebo, for 6 weeks. Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs) were assessed. RESULTS In all, 277 symptomatic patients were included in this post hoc analysis. Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1) from baseline to week 6 at all time points over 24 hours versus placebo. In addition, improvements in FEV1 from baseline during the nighttime period were observed for Aclidinium versus tiotropium on day 1 (Aclidinium 157 mL, tiotropium 67 mL; P<0.001) and week 6 (Aclidinium 153 mL, tiotropium 90 mL; P<0.05). Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (Aclidinium 136 mL, tiotropium 68 mL; P<0.05) and week 6 (Aclidinium 137 mL, tiotropium 71 mL; P<0.05). Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus tiotropium (except E-RS Chest Symptoms) and placebo over 6 weeks. Tolerability showed similar incidence of AEs in each arm. CONCLUSION In this post hoc analysis of symptomatic patients with moderate to severe COPD, Aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity.
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reduction in clinically important deterioration in chronic obstructive pulmonary disease with Aclidinium formoterol
Respiratory Research, 2017Co-Authors: Dave Singh, Ferran Chuecos, Anthony Durzo, Anna Munoz, Esther Garcia GilAbstract:Background ‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) Aclidinium Bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.
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the effect of Aclidinium Bromide on daily respiratory symptoms of copd measured using the evaluating respiratory symptoms in copd e rs copd diary pooled analysis of two 6 month phase iii studies
Respiratory Research, 2016Co-Authors: Paul W Jones, R Lamarca, Ferran Chuecos, Nancy Kline Leidy, Asha Hareendran, Esther Garcia GilAbstract:Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of Aclidinium Bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS). Data were pooled from the Aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating Aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A–D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed. Of 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, Aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for Aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with Aclidinium compared with placebo, in both GOLD Groups A + C and B + D. Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms. ATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 ).
Cynthia Caracta - One of the best experts on this subject based on the ideXlab platform.
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Aclidinium improves exercise endurance dyspnea lung hyperinflation and physical activity in patients with copd a randomized placebo controlled crossover trial
BMC Pulmonary Medicine, 2014Co-Authors: Kai M Beeh, Henrik Watz, Diana Jarreta, Esther Garcia Gil, Luis Puentemaestu, Luis De Teresa, Cynthia Caracta, Helgo MagnussenAbstract:Background 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.
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efficacy and safety of fixed dose combinations of Aclidinium Bromide formoterol fumarate the 24 week randomized placebo controlled augment copd study
Respiratory Research, 2014Co-Authors: Anthony Durzo, Edward Kerwin, Anne Leselbaum, Stephen I Rennard, Victor Mergel, Cynthia CaractaAbstract: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 400μg/formoterol 12μg (ACL400/FOR12 FDC), FDC Aclidinium 400μg/formoterol 6μg (ACL400/FOR6 FDC), Aclidinium 400μg, formoterol 12μg, 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 400μg/formoterol 12μg 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 . *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.
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efficacy and tolerability of Aclidinium Bromide formoterol fumarate fixed dose combination in patients with copd a 1 year study
European Respiratory Journal, 2014Co-Authors: Barry J Make, Anne Leselbaum, James F. Donohue, Xiaoyun Zhong, Weily Soong, Cynthia CaractaAbstract:BACKGROUND: In two 24-week placebo-controlled trials, twice-daily (BID) fixed-dose combination of Aclidinium 400µg/formoterol 12µg (FDC12) was safe and effective in COPD patients. AIMS: To evaluate long-term efficacy and safety of FDC12 in patients with moderate to severe COPD. METHODS: In this 1-year, double-blind, parallel-group study, patients were randomized (2:1) to FDC12 or formoterol 12µg (FOR) BID. Lung function, rescue medication use, and treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Mean baseline postbronchodilator FEV1 was 51.3% of predicted (ITT, n=581). In patients treated with FDC12, significant improvements from baseline in morning predose (trough) FEV1 were observed at each time point assessed vs FOR (Figure). In both treatment groups, average daily rescue medication use over the course of the study was reduced compared with baseline(FDC12, -1.8 puffs; FOR, -1.6 puffs). The percentage of patients with ≥1 TEAE was similar between FDC12 (71.4%) and FOR (65.7%) (safety population, n=590). The most common TEAEs (≥5% of patients in both groups) were sinusitis (5.1% vs 5.6%) and urinary tract infection (6.6% vs 5.6%). CONCLUSIONS: Sustained improvements in lung function were observed in patients with COPD treated with a fixed-dose combination of Aclidinium/formoterol for 1 year compared with formoterol. FDC tolerability was comparable to formoterol alone. ![Figure][1] [1]: pending:yes
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long term safety and efficacy of twice daily Aclidinium Bromide in patients with copd
Respiratory Medicine, 2013Co-Authors: Arthur F Gelb, Esther Garcia Gil, Donald P Tashkin, Barry J Make, Xiaoyun Zhong, Cynthia CaractaAbstract:Summary Background Aclidinium is a novel, long-acting muscarinic antagonist indicated for maintenance treatment of COPD. Methods In this 52-week, parallel-group, double-blind study, patients with moderate-to-severe COPD were randomized (1:1) to receive Aclidinium twice-daily (BID) 200 μg or 400 μg via a novel, dry powder inhaler (Genuair ® /Pressair ® ) [Registered trademarks of Almirall, SA, Barcelona, Spain for use within the European Union, Iceland, Norway, and Switzerland as Genuair ® and within the United States as Pressair ® ]. Safety, the primary objective, was assessed via adverse events (AEs), clinical laboratory tests, vital signs, and 12-lead electrocardiograms. Efficacy was evaluated using spirometry, SGRQ, and rescue medication use. Results A total of 605 patients were randomized in the study. The percentage of patients reporting any treatment-emergent AE (TEAE) was comparable between groups; most TEAEs were mild or moderate. Anticholinergic TEAEs were reported by low percentages of patients in either treatment group (dry mouth: 200 μg, 1.3%; 400 μg, 2.7%; constipation: 200 μg, 2.9%; 400 μg, 1.7%). Cardiac TEAEs were also reported by a low percentage of patients ( 1 , with numerically greater increases observed with the higher dose. Clinically important improvements in SGRQ scores and a reduction in rescue medication use were observed throughout the study for both doses. Conclusions Long-term treatment with Aclidinium 200 μg or 400 μg BID was well tolerated, with sustained benefits in lung function and health status in patients with COPD throughout the 1-year study. Clinical trial registration number NCT01044459.
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accord copd ii a randomized clinical trial to evaluate the 12 week efficacy and safety of twice daily Aclidinium Bromide in chronic obstructive pulmonary disease patients
Clinical Drug Investigation, 2013Co-Authors: Stephen I Rennard, Esther Garcia Gil, Paul D Scanlon, Gary T Ferguson, Ludmyla Rekeda, Brian Maurer, Cynthia CaractaAbstract:Background and Objectives Aclidinium Bromide is a long-acting muscarinic antagonist approved for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). This 12-week phase III study evaluated efficacy and tolerability of Aclidinium 200 or 400 μg in patients with moderate-to-severe COPD.
Paul W Jones - One of the best experts on this subject based on the ideXlab platform.
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the effect of Aclidinium Bromide on daily respiratory symptoms of copd measured using the evaluating respiratory symptoms in copd e rs copd diary pooled analysis of two 6 month phase iii studies
Respiratory Research, 2016Co-Authors: Paul W Jones, R Lamarca, Ferran Chuecos, Nancy Kline Leidy, Asha Hareendran, Esther Garcia GilAbstract:Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of Aclidinium Bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS). Data were pooled from the Aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating Aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A–D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed. Of 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, Aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for Aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with Aclidinium compared with placebo, in both GOLD Groups A + C and B + D. Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms. ATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 ).
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clinical potential of Aclidinium Bromide in chronic obstructive pulmonary disease
International Journal of Chronic Obstructive Pulmonary Disease, 2015Co-Authors: Paul W JonesAbstract:Three long-acting muscarinic antagonists (LAMAs) are now available in Europe, providing clinicians and patients with a choice of interventions, which is important in COPD, which is clinically a heterogeneous disease. The first LAMA, tiotropium, has been widely used over the last decade as a once-daily maintenance therapy in stable COPD to improve patients' health-related quality of life and to reduce the risk of exacerbations. Administered via the HandiHaler(®) device, it is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also been shown to improve health status and reduce exacerbations, and is well tolerated. The subject of this review is a third LAMA, Aclidinium Bromide, which was approved as a twice-daily maintenance bronchodilator treatment. In the pivotal Phase III clinical trials, patients receiving Aclidinium achieved significantly greater improvements in lung function, reductions in breathlessness, and improvements in health status compared with placebo, for up to 24 weeks. In continuation studies, these improvements were sustained for up to 52 weeks. Pooled data showed exacerbation frequency was significantly reduced with Aclidinium versus placebo. Preclinical and pharmacological studies demonstrating low systemic bioavailability and a low propensity to induce cardiac arrhythmias were translated into a favorable tolerability profile in the clinical trial program - the adverse event profile of Aclidinium was similar to placebo, with a low incidence of anticholinergic and cardiac adverse events. While additional studies are needed to evaluate its full clinical potential, Aclidinium is an important part of this recent expansion of LAMA therapeutic options, providing clinicians and patients with an effective and well-tolerated COPD treatment.
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effects of Aclidinium Bromide formoterol fumarate fixed dose combination on health status in copd
Pneumologie, 2015Co-Authors: Paul W Jones, Dave Singh, Paul D Scanlon, Victor Mergel, Eduard Molins, Stephanie Korn, Anne LeselbaumAbstract:Background Aclidinium/formoterol fixed-dose combination (FDC) is in development for the management of COPD. The ACLIFORM and AUGMENT studies assessed the effects of twice-daily FDC on health status in patients with moderate to severe COPD. Method ACLIFORM and AUGMENT were multinational, double-blind, placebo- and active-controlled, parallel-group studies. Patients were randomized to receive placebo, Aclidinium 400 µg, formoterol 12 µg, FDC 400/6 µg or FDC 400/12 µg. Change from baseline in SGRQ total score at Week 24 and the percentage of patients achieving or exceeding the MCID (≥4 units) were assessed. Results In total, 1726 (mean age 63.2 years; 67.6% male; moderate COPD 60.1%; mean baseline SGRQ score 46.2) and 1668 (mean age 63.9 years; 53.2% male; moderate COPD 57.0%; mean baseline SGRQ score 46.0) patients were included in the ITT population in ACLIFORM and AUGMENT, respectively. In both studies, both FDC doses improved SGRQ total score by ≥MCID at Week 24 and >50% of patients receiving FDC achieved or exceeded the MCID (Table). In ACLIFORM, improvements in SGRQ total score with FDC did not reach significance versus placebo, possibly due to a very large placebo response (>MCID). Conclusion These studies indicate that Aclidinium/formoterol FDC improves health status in patients with moderate to severe COPD, notwithstanding the large placebo effect that may have masked the treatment effect in ACLIFORM. ![Figure][1] [1]: pending:yes
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p189 reduced copd exacerbations associated with Aclidinium Bromide versus placebo a pooled analysis of phase iii data
Thorax, 2012Co-Authors: Paul W Jones, Edward Kerwin, R Lamarca, Cynthia Caracta, Dave Singh, Esther Garcia GilAbstract:Introduction and objective Aclidinium Bromide is a novel, long-acting, inhaled muscarinic antagonist indicated for the treatment of chronic obstructive pulmonary disease (COPD). COPD is characterised by periodic worsening of symptoms (exacerbations) that are associated with increased morbidity and mortality. Here, we report the results of a pooled analysis of Aclidinium on exacerbations. Methods Data from two Phase III studies (3-month ACCORD COPD I and 6-month ATTAIN) were included in this analysis . Both were designed to evaluate the efficacy and safety of Aclidinium 200 µg and 400 µg (metered dose) BID versus placebo (primary endpoint: change from baseline in FEV1). Adults (aged ≥40 years) with moderate-to-severe COPD, who were current/former smokers with a smoking history ≥10 pack-years, were included. Exacerbations (additional endpoint) were assessed in both studies using healthcare resource utilisation (HCRU) criteria (increase in symptoms for ≥2 consecutive days that required increased medication use or other medical intervention) and, in ATTAIN only, with the Exacerbations of Chronic Pulmonary Disease Tool (EXACT [daily diary card data with exacerbations defined according to the developer’s criteria]). Neither study was individually powered to assess treatment differences in exacerbation frequency. In this pooled analysis, exacerbation rate ratios (per patient/year for Aclidinium versus placebo) were analyzed using a Poisson regression model corrected for over-dispersion; 95% confidence intervals and p-values were calculated. Results Data for 1378 patients were included; the majority (62%) were male with a mean age of approximately 63 years. At baseline, >60% of patients were classed as GOLD stage II (moderate), and 31% reported ≥1 exacerbations in the previous 12 months. In both studies, there was a trend towards relative reduction (approximately 30%) in the rate of moderate or severe exacerbations (requiring antibiotic or corticosteroid treatment, or hospitalisation) with both Aclidinium doses versus placebo ([F][1]igure). A significant reduction in moderate or severe exacerbation rate was observed with Aclidinium 400 µg versus placebo when data from both studies were pooled (0.31 vs 0.44; rate ratio 0.71, p=0.01). ![Abstract P189 Figure 1][2] Abstract P189 Figure 1 Conclusions This pooled analysis provides evidence to support a reduction in moderate or severe COPD exacerbations with Aclidinium 200 µg and 400 µg BID compared with placebo. [1]: #F1 [2]: pending:yes
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efficacy and safety of twice daily Aclidinium Bromide in copd patients the attain study
European Respiratory Journal, 2012Co-Authors: Paul W Jones, R Lamarca, Rosa Segarra, Dave Singh, Gonzalo De Miquel, Eric D Bateman, Alvar Agusti, Cynthia CaractaAbstract: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 George9s 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 1 (185 and 209 mL; both p 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 Twice-daily Aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.
Dave Singh - One of the best experts on this subject based on the ideXlab platform.
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Aclidinium Bromide formoterol fumarate as a treatment for copd an update
Expert Review of Respiratory Medicine, 2021Co-Authors: Anthony Durzo, James F. Donohue, Dave Singh, Kenneth R Chapman, Robert A WiseAbstract:Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of Aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.Areas covered: This review examines recent research findings that expand our understanding of the impact of Aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of Aclidinium and current LAMA/LABA treatment recommendations are discussed.Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naive, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with Aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.
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Aclidinium Bromide in fixed-dose combination with formoterol fumarate in the management of COPD: an update on the evidence base
SAGE Publishing, 2019Co-Authors: Anthony D. D’urzo, James F. Donohue, Dave Singh, Kenneth R ChapmanAbstract:Aclidinium Bromide/formoterol fumarate (AB/FF) 400/12 µg is a twice-daily long-acting muscarinic receptor antagonist and long-acting β 2 agonist (LAMA/LABA) dual-bronchodilator maintenance therapy used to relieve symptoms and reduce future risk of exacerbations in adults with chronic obstructive pulmonary disease (COPD). To date, there have been several clinical studies and post hoc analyses of AB/FF, assessing treatment outcomes in patients with moderate-to-severe COPD. These studies have looked at a range of outcomes, including lung function parameters, patient-reported symptom scores, quality-of-life measures assessing impaired health and perceived well-being, and the frequency, duration, and severity of exacerbations. In light of the major 2017 revision to the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, and the subsequent updates, we present an update on the latest evidence supporting the efficacy and safety of AB/FF. This review discusses the clinical relevance of the improvements in lung function, symptoms, quality of life, and exacerbations in patients with COPD reported in the phase III and IV trials of AB/FF. Given the current concerns over unnecessary inhaled corticosteroid (ICS) use in COPD, we also touch briefly on the use of blood eosinophils as a biomarker for identifying those patients with COPD already using LAMA/LABA therapy for whom the addition of ICS might be of benefit
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reduction in clinically important deterioration in chronic obstructive pulmonary disease with Aclidinium formoterol
Respiratory Research, 2017Co-Authors: Dave Singh, Ferran Chuecos, Anthony Durzo, Anna Munoz, Esther Garcia GilAbstract:Background ‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) Aclidinium Bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.
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Aclidinium Bromide and formoterol fumarate as a fixed dose combination in copd pooled analysis of symptoms and exacerbations from two six month multicentre randomised studies acliform and augment
Respiratory Research, 2015Co-Authors: Eric D Bateman, Anne Leselbaum, Dave Singh, Kenneth R Chapman, Anthony Durzo, Eduard Molins, Esther Garcia GilAbstract:The combination of Aclidinium Bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT). Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily Aclidinium/formoterol 400/12 μg or 400/6 μg, Aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed. The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with Aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with Aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with Aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and Aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with Aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with Aclidinium/formoterol 400/12 μg versus placebo and Aclidinium (p < 0.01). Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, Aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, Aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo. NCT01462942 and NCT01437397 (ClinicalTrials.gov)
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effects of Aclidinium Bromide formoterol fumarate fixed dose combination on health status in copd
Pneumologie, 2015Co-Authors: Paul W Jones, Dave Singh, Paul D Scanlon, Victor Mergel, Eduard Molins, Stephanie Korn, Anne LeselbaumAbstract:Background Aclidinium/formoterol fixed-dose combination (FDC) is in development for the management of COPD. The ACLIFORM and AUGMENT studies assessed the effects of twice-daily FDC on health status in patients with moderate to severe COPD. Method ACLIFORM and AUGMENT were multinational, double-blind, placebo- and active-controlled, parallel-group studies. Patients were randomized to receive placebo, Aclidinium 400 µg, formoterol 12 µg, FDC 400/6 µg or FDC 400/12 µg. Change from baseline in SGRQ total score at Week 24 and the percentage of patients achieving or exceeding the MCID (≥4 units) were assessed. Results In total, 1726 (mean age 63.2 years; 67.6% male; moderate COPD 60.1%; mean baseline SGRQ score 46.2) and 1668 (mean age 63.9 years; 53.2% male; moderate COPD 57.0%; mean baseline SGRQ score 46.0) patients were included in the ITT population in ACLIFORM and AUGMENT, respectively. In both studies, both FDC doses improved SGRQ total score by ≥MCID at Week 24 and >50% of patients receiving FDC achieved or exceeded the MCID (Table). In ACLIFORM, improvements in SGRQ total score with FDC did not reach significance versus placebo, possibly due to a very large placebo response (>MCID). Conclusion These studies indicate that Aclidinium/formoterol FDC improves health status in patients with moderate to severe COPD, notwithstanding the large placebo effect that may have masked the treatment effect in ACLIFORM. ![Figure][1] [1]: pending:yes
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Aclidinium Bromide formoterol fumarate as a treatment for copd an update
Expert Review of Respiratory Medicine, 2021Co-Authors: Anthony Durzo, James F. Donohue, Dave Singh, Kenneth R Chapman, Robert A WiseAbstract:Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of Aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.Areas covered: This review examines recent research findings that expand our understanding of the impact of Aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of Aclidinium and current LAMA/LABA treatment recommendations are discussed.Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naive, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with Aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.
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reduction in clinically important deterioration in chronic obstructive pulmonary disease with Aclidinium formoterol
Respiratory Research, 2017Co-Authors: Dave Singh, Ferran Chuecos, Anthony Durzo, Anna Munoz, Esther Garcia GilAbstract:Background ‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) Aclidinium Bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.
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Aclidinium Bromide and formoterol fumarate as a fixed dose combination in copd pooled analysis of symptoms and exacerbations from two six month multicentre randomised studies acliform and augment
Respiratory Research, 2015Co-Authors: Eric D Bateman, Anne Leselbaum, Dave Singh, Kenneth R Chapman, Anthony Durzo, Eduard Molins, Esther Garcia GilAbstract:The combination of Aclidinium Bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT). Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily Aclidinium/formoterol 400/12 μg or 400/6 μg, Aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed. The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with Aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with Aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with Aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and Aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with Aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with Aclidinium/formoterol 400/12 μg versus placebo and Aclidinium (p < 0.01). Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, Aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, Aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo. NCT01462942 and NCT01437397 (ClinicalTrials.gov)
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efficacy and safety of fixed dose combinations of Aclidinium Bromide formoterol fumarate the 24 week randomized placebo controlled augment copd study
Respiratory Research, 2014Co-Authors: Anthony Durzo, Edward Kerwin, Anne Leselbaum, Stephen I Rennard, Victor Mergel, Cynthia CaractaAbstract: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 400μg/formoterol 12μg (ACL400/FOR12 FDC), FDC Aclidinium 400μg/formoterol 6μg (ACL400/FOR6 FDC), Aclidinium 400μg, formoterol 12μg, 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 400μg/formoterol 12μg 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 . *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.
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one year extension study of accord copd i safety and efficacy of two doses of twice daily Aclidinium Bromide in patients with copd
COPD: Journal of Chronic Obstructive Pulmonary Disease, 2013Co-Authors: Anthony Durzo, Edward Kerwin, Esther Garcia Gil, Stephen I Rennard, Cynthia CaractaAbstract:AbstractThis 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% fo...
