المؤلفون: Li,Weimin, Daoud,Sami, Trivedi,Roopa, Lukka,Pradeep, Jimenez,Eulalia, Molins,Eduard, Stewart,Catherine, Bharali,Pranob, Garcia-Gil,Esther

مصطلحات موضوعية: International Journal of Chronic Obstructive Pulmonary Disease

الوصف: Weimin Li,1 Sami Z Daoud,2 Roopa Trivedi,3 Pradeep B Lukka,4 Eulalia Jimenez,5 Eduard Molins,5 Catherine Stewart,6 Pranob Bharali,3,7 Esther Garcia-Gil8 1Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Late Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Durham, NC, USA; 4Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA; 5Clinical & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Barcelona, Spain; 6Statistics, Phastar, Chiswick, London, UK; 7BioPharmaceuticals R&D Late-Stage Development, AstraZeneca India Pvt Ltd., Bangalore, Karnataka, India; 8Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Barcelona, SpainCorrespondence: Sami Z Daoud, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 302-598-8614, Email Sami.Daoud@astrazeneca.comPurpose: To date, aclidinium pharmacokinetic (PK) studies have focused on Caucasian populations, and no data are available for Chinese populations. We aimed to characterize the PK and safety profile of aclidinium and its metabolites (LAS34823 and LAS34850) following single and multiple (twice-daily; BID) dosing in healthy Chinese participants, and to compare PK data between Chinese and Caucasian populations.Materials and methods: In this Phase I, open-label study (NCT03276052), healthy participants from a single site in China received aclidinium bromide 400 μg via a dry powder inhaler. The Day 1 single dose was followed by a washout period of 96 hours. On Days 5 through 8, participants received BID doses.Results: Twenty healthy Chinese participants, aged 18– 45 years, were enrolled. Aclidinium absorption was rapid (median time to maximum concentration [tmax] ...

وصف الملف: text/html

العلاقة: https://www.dovepress.com/the-pharmacokinetics-safety-and-tolerability-of-aclidinium-bromide-400-peer-reviewed-fulltext-article-COPDTest

الإتاحة: https://doi.org/10.2147/COPD.S434588Test
https://www.dovepress.com/the-pharmacokinetics-safety-and-tolerability-of-aclidinium-bromide-400-peer-reviewed-fulltext-article-COPDTest

المؤلفون: Li, Weimin, Daoud, Sami, Trivedi, Roopa, Lukka, Pradeep, Jimenez, Eulalia, Molins, Eduard, Stewart, Catherine, Bharali, Pranob, Garcia-Gil, Esther

المصدر: International Journal of Chronic Obstructive Pulmonary Disease ; volume Volume 18, page 2725-2735 ; ISSN 1178-2005

الإتاحة: https://doi.org/10.2147/copd.s434588Test
https://www.dovepress.com/getfile.php?fileID=94687Test

المؤلفون: Sun, Yongchang, Molins, Eduard, Daoud, Sami Z., Trivedi, Roopa, Stewart, Catherine, Lamarca, Rosa, Bharali, Pranob, Garcia-Gil, Esther

المساهمون: AstraZeneca plc

المصدر: Respiratory Medicine ; volume 218, page 107393 ; ISSN 0954-6111

مصطلحات موضوعية: Pulmonary and Respiratory Medicine

الإتاحة: https://doi.org/10.1016/j.rmed.2023.107393Test
https://api.elsevier.com/content/article/PII:S0954611123002810?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0954611123002810?httpAccept=text/plainTest

المؤلفون: van den Berge, Maarten, De Backer, Jan, van Holsbeke, Cedric, De Backer, Wilfried A.K., Trivedi, Roopa, Jenkins, Martin, Dorinsky, Paul, Aurivillius, Magnus

المصدر: 1465-9921 ; Respiratory research

مصطلحات موضوعية: Human medicine

الوصف: Background: For patients with chronic obstructive pulmonary disease (COPD), greater improvements in lung function have been demonstrated for triple versus dual inhaled therapies in traditional spirometry studies. This study was the first to use functional respiratory imaging (FRI), known for increased sensitivity to airway changes versus spirometry, to assess the effect of the inhaled corticosteroid (ICS) component (budesonide) on lung function in patients with moderate-to-severe COPD and a blood eosinophil count > 150 cells/mm(3). Methods: Patients in this Phase IIIb (NCT03836677), randomized, double-blind, crossover study received twice-daily budesonide/glycopyrrolate/formoterol fumarate (BGF) 320/18/9.6 mu g fixed-dose triple therapy and glycopyrrolate/formoterol fumarate (GFF) 18/9.6 mu g fixed-dose dual therapy over 4 weeks, each delivered via a single metered dose Aerosphere inhaler. Primary endpoints were the improvements from baseline for each treatment in specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and resistance (siRaw) measured via FRI taken at total lung capacity (Day 29). Secondary outcomes included spirometry and body plethysmography. Adverse events were monitored throughout the study. Results: A total of 23 patients were randomized and included in the intent-to-treat analysis (mean age 64.9 years, 78.3% males, 43.5% current smokers, mean predicted post-bronchodilator forced expiratory volume in 1 s [FEV1] 63.6%). BGF and GFF both statistically significantly increased siVaw from baseline at Day 29 (geometric mean ratio [GM], 95% confidence interval [CI]: 1.72 [1.38, 2.13] and 1.53 [1.28, 1.83], respectively, both p < 0.0001), with a greater increase observed for BGF versus GFF (GM, 95% CI 1.09 [1.03, 1.16], p = 0.0061). Statistically significant reductions in siRaw were also observed with both BGF and GFF (GM, 95% CI 0.50 [0.39, 0.63] and 0.52 [0.40, 0.67], respectively, both p < 0.0001). Additionally, significant improvements from baseline in ...

العلاقة: info:eu-repo/semantics/altIdentifier/isi/000671816600002

الإتاحة: https://doi.org/10.1186/S12931-021-01772-2Test
https://hdl.handle.net/10067/1797760151162165141Test
https://repository.uantwerpen.be/docstore/d:irua:7455Test

المؤلفون: Usmani, Omar, Roche, Nicolas, Wahab, Ezanul, Israel, Samuel, Jenkins, Martin, Trivedi, Roopa, Dorinsky, Paul, Aurivillius, Magnus

المساهمون: AstraZeneca

المصدر: Respiratory Research ; volume 22, issue 1 ; ISSN 1465-993X

الوصف: Background Triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β 2 -agonists (ICS/LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD. Methods This phase I, single-dose, open-label gamma scintigraphy imaging study (NCT03906045) was conducted in patients with moderate-to-very severe COPD. Patients received two actuations of BGF MDI (160/9/4.8 μg per actuation) radiolabeled with technetium‑99‑pertechnetate, not exceeding 5 MBq per actuation. Immediately following each inhalation, patients performed a breath-hold of up to 10 s, then exhaled into an exhalation filter. Gamma scintigraphy imaging of the anterior and posterior views of the lungs and stomach, and a lateral head and neck view, were performed immediately after exhalation. The primary objective of the study was to assess the pulmonary deposition of BGF. Secondary objectives assessed the deposited dose of radiolabeled BGF in the oropharyngeal and stomach regions, on the actuator, and on the exhalation filter in addition to regional airway deposition patterns in the lungs. Results The mean BGF emitted dose deposited in the lungs was 32.1% (standard deviation [SD] 15.6) in patients with moderate-to-very severe COPD, 35.2% (SD 12.8) in patients with moderate COPD, and 28.7% (SD 18.4) in patients with severe/very severe COPD. Overall, the mean normalized outer/inner ratio was 0.55 (SD 0.19), while the ...

الإتاحة: https://doi.org/10.1186/s12931-021-01813-wTest

المؤلفون: Rabe, Klaus F., Martinez, Fernando J., Singh, Dave, Trivedi, Roopa, Jenkins, Martin, Darken, Patrick, Aurivillius, Magnus, Dorinsky, Paul

المساهمون: AstraZeneca

المصدر: Therapeutic Advances in Respiratory Disease ; volume 15, page 175346662110343 ; ISSN 1753-4666 1753-4666

مصطلحات موضوعية: Pharmacology (medical), Pulmonary and Respiratory Medicine

الوصف: Background: In the phase III, 52-week ETHOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF), at two inhaled corticosteroid dose levels, resulted in significantly lower moderate/severe exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) and budesonide/formoterol fumarate (BFF). Here, we report results from the ETHOS pulmonary function test (PFT) sub-study, which assessed lung function in a subset of ETHOS patients. Methods: ETHOS (NCT02465567) was a randomized, double-blind, multi-center, parallel-group study in patients with moderate to very severe COPD who had experienced ⩾1 moderate/severe exacerbation in the previous year. Patients received BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF 18/9.6 µg, or BFF 320/9.6 µg twice daily via a single metered dose Aerosphere inhaler for 52 weeks. A subset of patients participated in the 4-hour PFT sub-study; primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV 1 ) versus GFF and FEV 1 area under the curve from 0 to 4 hours (AUC 0–4 ) versus BFF at week 24. Results: The PFT modified intent-to-treat population included 3088 patients (mean age 64.4 years; mean reversibility post-albuterol 16.7%; mean post-albuterol FEV 1 % predicted 42.8). BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved morning pre-dose trough FEV 1 at week 24 versus GFF ( p ⩽ 0.0035 for both). Improvements in trough FEV 1 were also observed at week 52 for BGF 320/18/9.6 µg and 160/18/9.6 µg versus GFF ( p ⩽ 0.0005 for both). For FEV 1 AUC 0–4 at week 24, BGF 320/18/9.6 µg and 160/18/9.6 µg showed significant improvements versus BFF ( p < 0.0001 for both). Improvements were maintained at week 52 ( p < 0.0001). Conclusions: BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved trough FEV 1 versus GFF and FEV 1 AUC 0–4 versus BFF at week 24. The lung function benefits with both doses of BGF were ...

الإتاحة: https://doi.org/10.1177/17534666211034329Test

المؤلفون: Martinez, Fernando J., Rabe, Klaus F., Ferguson, Gary T., Wedzicha, Jadwiga A., Trivedi, Roopa, Jenkins, Martin, Darken, Patrick, Aurivillius, Magnus, Dorinsky, Paul

المصدر: Respiratory Medicine ; volume 185, page 106509 ; ISSN 0954-6111

مصطلحات موضوعية: Pulmonary and Respiratory Medicine

الإتاحة: https://doi.org/10.1016/j.rmed.2021.106509Test
https://api.elsevier.com/content/article/PII:S0954611121002158?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0954611121002158?httpAccept=text/plainTest

المؤلفون: Rabe, Klaus F, Martinez, Fernando J, Ferguson, Gary T, Wang, Chen, Singh, Dave, Wedzicha, Jadwiga A, Trivedi, Roopa, St Rose, Earl, Ballal, Shaila, McLaren, Julie, Darken, Patrick, Aurivillius, Magnus, Reisner, Colin, Dorinsky, Paul, ETHOS Investigators, Martinot, Jean-Benoit

المساهمون: UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie

المصدر: The New England journal of medicine, Vol. 383, no.1, p. 35-48 (2020)

مصطلحات موضوعية: Administration, Inhalation, Adrenergic beta-2 Receptor Agonists, Adult, Aged, 80 and over, Budesonide, Double-Blind Method, Drug Combinations, Female, Forced Expiratory Volume, Formoterol Fumarate, Glucocorticoids, Glycopyrrolate, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Muscarinic Antagonists, Pulmonary Disease, Chronic Obstructive

الوصف: Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking. In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only. The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg-budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg-budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate-formoterol group (2120 patients), and 1.24 in the budesonide-formoterol group (2131 patients). The rate was significantly lower with 320-μg-budesonide triple therapy than with glycopyrrolate-formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide-formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P = 0.003). Similarly, the rate was significantly lower with 160-μg-budesonide triple therapy than with glycopyrrolate-formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide-formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 ...

العلاقة: boreal:283505; http://hdl.handle.net/2078.1/283505Test; info:pmid/32579807; urn:EISSN:1533-4406

الإتاحة: https://doi.org/10.1056/NEJMoa1916046Test
http://hdl.handle.net/2078.1/283505Test

المؤلفون: Dorinsky, Paul, DePetrillo, Paolo, DeAngelis, Kiernan, Trivedi, Roopa, Darken, Patrick, Gillen, Michael

المساهمون: AstraZeneca

المصدر: Clinical Therapeutics ; volume 42, issue 4, page 634-648 ; ISSN 0149-2918

الإتاحة: https://doi.org/10.1016/j.clinthera.2020.02.012Test
https://api.elsevier.com/content/article/PII:S0149291820301144?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0149291820301144?httpAccept=text/plainTest

المؤلفون: Usmani, Omar, Roche, Nicolas, Abd Wahab, Ezanul, Israel, Samuel, Jenkins, Martin, Trivedi, Roopa, Dorinsky, Paul, Aurivillius, Magnus

المصدر: Chest ; volume 158, issue 4, page A2435-A2437 ; ISSN 0012-3692

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, Pulmonary and Respiratory Medicine

الإتاحة: https://doi.org/10.1016/j.chest.2020.09.023Test
https://api.elsevier.com/content/article/PII:S0012369220343890?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0012369220343890?httpAccept=text/plainTest