The Experts below are selected from a list of 1575 Experts worldwide ranked by ideXlab platform
Paul Dorinsky - One of the best experts on this subject based on the ideXlab platform.
-
budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler improves exacerbation outcomes in patients with copd without a recent exacerbation history a subgroup analysis of kronos
International Journal of Chronic Obstructive Pulmonary Disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and Methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.
International journal of chronic obstructive pulmonary disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
efficacy and safety of two doses of budesonide Formoterol Fumarate metered dose inhaler in copd
ERJ Open Research, 2020Co-Authors: Nicola A Hanania, Fernando J Martinez, Alberto Papi, Antonio Anzueto, K Rossman, C Cappelletti, Elizabeth A Duncan, Jack Nyberg, Paul DorinskyAbstract:Inhaled corticosteroid/long-acting β2-agonist combination therapy is a recommended treatment option for patients with chronic obstructive pulmonary disease (COPD) and increased exacerbation risk, particularly those with elevated blood eosinophil levels. SOPHOS (NCT02727660) evaluated the efficacy and safety of two doses of budesonide/Formoterol Fumarate dihydrate metered dose inhaler (BFF MDI) versus Formoterol Fumarate dihydrate (FF) MDI, each delivered using co-suspension delivery technology, in patients with moderate-to-very severe COPD and a history of exacerbations. In this phase 3, randomised, double-blind, parallel-group, 12-52-week, variable length study, patients received twice-daily BFF MDI 320/10 µg or 160/10 µg, or FF MDI 10 µg. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) at week 12. Secondary and other endpoints included assessments of moderate/severe COPD exacerbations and safety. The primary analysis (modified intent-to-treat) population included 1843 patients (BFF MDI 320/10 µg, n=619; BFF MDI 160/10 µg, n=617; and FF MDI, n=607). BFF MDI 320/10 µg and 160/10 µg improved morning pre-dose trough FEV1 at week 12 versus FF MDI (least squares mean differences 34 mL [p=0.0081] and 32 mL [p=0.0134], respectively), increased time to first exacerbation (hazard ratios 0.827 [p=0.0441] and 0.803 [p=0.0198], respectively) and reduced exacerbation rate (rate ratios 0.67 [p=0.0001] and 0.71 [p=0.0010], respectively). Lung function and exacerbation benefits were driven by patients with blood eosinophil counts ≥150 cells·mm-3. The incidence of adverse events was similar, and pneumonia rates were low (≤2.4%) across treatments. SOPHOS demonstrated the efficacy and tolerability of BFF MDI 320/10 µg and 160/10 µg in patients with moderate-to-very severe COPD at increased risk of exacerbations.
-
efficacy and safety of budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler in chinese patients with copd a subgroup analysis of kronos
Advances in Therapy, 2020Co-Authors: Chen Wang, Kiernan Deangelis, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Pryseley Nkouibert Assam, Eric Bourne, Shaila Ballal, Paul DorinskyAbstract:This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12–24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint. In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference − 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated. Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD. ClinicalTrials.gov NCT02497001.
-
Pharmacokinetics of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD.
Pulmonary pharmacology & therapeutics, 2019Co-Authors: Leonard J. Dunn, Kiernan Deangelis, Edward Kerwin, Patrick Darken, Michael Gillen, Paul DorinskyAbstract:Abstract Background Budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, is a triple fixed-dose combination in late-stage clinical development for chronic obstructive pulmonary disease (COPD). Methods We conducted two studies to characterize the pharmacokinetic (PK) profile of BGF MDI in patients with COPD: (i) a phase I, open-label, single and chronic (7-day) dosing study (NCT03250182) with one treatment arm (BGF MDI 320/18/9.6 μg); and (ii) a PK sub-study of KRONOS (NCT02497001), a phase III, randomized, double-blind study in which patients received 24 weeks’ treatment with BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 320/9 μg. PK parameters in both studies included maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from 0 to 12h (AUC0–12). Results In the phase I PK study (30 patients), budesonide and glycopyrronium Cmax were comparable after single and chronic dosing of BGF MDI (accumulation ratio [RAC] 95% and 107%, respectively) whereas Cmax for Formoterol was slightly higher after chronic dosing (RAC 116%). AUC0–12 for budesonide, glycopyrronium, and Formoterol were higher following chronic versus single dosing, with an RAC of 126%, 179%, and 143%, respectively. After 7 days’ dosing, AUC0–12 and Cmax for all three components of BGF MDI were similar to those in the KRONOS PK sub-study (202 patients) at Week 24. In the latter sub-study, Cmax and AUC0–12 at Week 24 were generally comparable across treatments for budesonide (geometric mean ratios [GMR] of 96%–109% for BGF MDI vs BFF MDI or BUD/FORM DPI), glycopyrronium (GMR of 88%–100% for BGF MDI vs GFF MDI), and Formoterol (GMR of 80%–113% for BGF MDI vs GFF MDI or BFF MDI). Conclusions Steady-state PK parameters of budesonide, glycopyrronium, and Formoterol were similar after 7 days’ dosing in the phase I PK study and after 24 weeks in the KRONOS PK sub-study. Systemic exposure to budesonide, glycopyrronium, and Formoterol was generally comparable across treatments in the KRONOS PK sub-study, suggesting no meaningful drug–drug or within-formulation PK interactions.
Gary T. Ferguson - One of the best experts on this subject based on the ideXlab platform.
-
budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler improves exacerbation outcomes in patients with copd without a recent exacerbation history a subgroup analysis of kronos
International Journal of Chronic Obstructive Pulmonary Disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and Methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.
International journal of chronic obstructive pulmonary disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD.
International journal of chronic obstructive pulmonary disease, 2019Co-Authors: Masakazu Ichinose, Gary T. Ferguson, Yasushi Fukushima, Yoshikazu Inoue, Osamu Hataji, Klaus F. Rabe, Nobuya Hayashi, Hiroshi Okada, Mami Takikawa, Eric BourneAbstract:Background Budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) is a triple fixed-dose combination for COPD. The long-term safety of triple therapy for COPD has not been investigated in Japanese patients. In this 28-week extension study (NCT03262012), we investigated the long-term safety and tolerability of BGF MDI in Japanese patients with moderate-to-very severe COPD who completed the 24-week Phase III randomized, double-blind, multicenter KRONOS study (NCT02497001). Materials and methods Patients randomized to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice-daily in KRONOS continued treatment for up to 28 additional weeks. Safety was evaluated over 52 weeks via adverse event (AE) monitoring, electrocardiograms, clinical laboratory testing, and vital sign measurements. Results The safety population included 416 patients who received BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Treatment-emergent AE (TEAE) rates were similar across treatment groups (range: 82.6-82.9%). The most frequent TEAEs overall were nasopharyngitis (32.2%) and bronchitis (9.9%). The incidence of major adverse cardiovascular events was low across groups (range: 0.0-2.9%). Over 52 weeks, the incidence of confirmed pneumonia was 9.4% (BGF MDI), 3.6% (GFF MDI), 5.7% (BFF MDI), and 2.9% (BUD/FORM DPI); in the 28-week extension period, rates were comparable across groups (range: 2.9-5.7%). Six deaths were reported (0.7-2.2% per group); none were considered treatment-related. No clinically meaningful trends were observed in electrocardiograms, laboratory parameters, or vital signs over time in any of the treatment groups. Conclusion All treatments were well tolerated over 52 weeks, and the safety profile of BGF MDI was generally comparable to dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) and inhaled corticosteroid (ICS)/LABA therapies. These findings support the long-term tolerability of BGF MDI in Japanese patients with COPD.
-
long term safety and efficacy of budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler formulated using co suspension delivery technology in japanese patients with copd
International Journal of Chronic Obstructive Pulmonary Disease, 2019Co-Authors: Masakazu Ichinose, Gary T. Ferguson, Yasushi Fukushima, Yoshikazu Inoue, Osamu Hataji, Klaus F. Rabe, Nobuya Hayashi, Hiroshi Okada, Mami Takikawa, Eric BourneAbstract:Background Budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) is a triple fixed-dose combination for COPD. The long-term safety of triple therapy for COPD has not been investigated in Japanese patients. In this 28-week extension study (NCT03262012), we investigated the long-term safety and tolerability of BGF MDI in Japanese patients with moderate-to-very severe COPD who completed the 24-week Phase III randomized, double-blind, multicenter KRONOS study (NCT02497001). Materials and methods Patients randomized to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice-daily in KRONOS continued treatment for up to 28 additional weeks. Safety was evaluated over 52 weeks via adverse event (AE) monitoring, electrocardiograms, clinical laboratory testing, and vital sign measurements. Results The safety population included 416 patients who received BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Treatment-emergent AE (TEAE) rates were similar across treatment groups (range: 82.6-82.9%). The most frequent TEAEs overall were nasopharyngitis (32.2%) and bronchitis (9.9%). The incidence of major adverse cardiovascular events was low across groups (range: 0.0-2.9%). Over 52 weeks, the incidence of confirmed pneumonia was 9.4% (BGF MDI), 3.6% (GFF MDI), 5.7% (BFF MDI), and 2.9% (BUD/FORM DPI); in the 28-week extension period, rates were comparable across groups (range: 2.9-5.7%). Six deaths were reported (0.7-2.2% per group); none were considered treatment-related. No clinically meaningful trends were observed in electrocardiograms, laboratory parameters, or vital signs over time in any of the treatment groups. Conclusion All treatments were well tolerated over 52 weeks, and the safety profile of BGF MDI was generally comparable to dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) and inhaled corticosteroid (ICS)/LABA therapies. These findings support the long-term tolerability of BGF MDI in Japanese patients with COPD.
-
Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD: A Subgroup Analysis of the KRONOS Study.
International journal of chronic obstructive pulmonary disease, 2019Co-Authors: Masakazu Ichinose, Gary T. Ferguson, Yasushi Fukushima, Yoshikazu Inoue, Osamu Hataji, Klaus F. Rabe, Nobuya Hayashi, Hiroshi Okada, Mami Takikawa, Eric BourneAbstract:Background KRONOS, a Phase III, multicenter, randomized, double-blind study (NCT02497001) conducted in Canada, China, Japan, and the USA, assessed the efficacy and safety of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI), a triple fixed-dose combination therapy, relative to dual therapies in patients with moderate-to-very severe COPD. Here we present findings from the Japanese subgroup of KRONOS. Methods Patients received BGF MDI 320/18/9.6μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12μg twice-daily for 24 weeks. The primary endpoint was the change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over Weeks 12-24. Symptoms, quality of life, exacerbations, and safety were also assessed. Results In total, 416 Japanese patients (21.9% of the global KRONOS population) were randomized and treated with BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Nominally significant improvements in the change from baseline in morning pre-dose trough FEV1 over Weeks 12-24 were observed for BGF MDI vs GFF MDI (least squares mean [LSM] difference 37 mL, 95% confidence interval [CI] 3, 72; P=0.0337) and BFF MDI (67 mL; 95% CI 25, 109; P=0.0020). Treatment with BGF MDI led to a nominally significant reduction in the rate of moderate/severe exacerbations vs GFF MDI (rate ratio 0.40, 95% CI 0.19, 0.83; P=0.0142). Compared with dual therapies, numerical improvements were observed with BGF MDI for Transition Dyspnea Index focal score and the change from baseline in Evaluating Respiratory Symptoms in COPD total score (P≤0.3899). All treatments were generally well tolerated. Conclusion BGF MDI nominally significantly improved lung function and numerically improved symptoms vs GFF MDI and BFF MDI. BGF MDI nominally significantly reduced exacerbations vs GFF MDI in Japanese patients with COPD. Efficacy and safety findings were generally comparable to those in the global KRONOS population.
Eric Bourne - One of the best experts on this subject based on the ideXlab platform.
-
budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler improves exacerbation outcomes in patients with copd without a recent exacerbation history a subgroup analysis of kronos
International Journal of Chronic Obstructive Pulmonary Disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and Methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.
International journal of chronic obstructive pulmonary disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in Chinese Patients with COPD: A Subgroup Analysis of KRONOS
Advances in therapy, 2020Co-Authors: Chen Wang, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Pryseley Nkouibert Assam, Eric Bourne, Shaila BallalAbstract:This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12–24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint. In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference − 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated. Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD. ClinicalTrials.gov NCT02497001.
-
efficacy and safety of budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler in chinese patients with copd a subgroup analysis of kronos
Advances in Therapy, 2020Co-Authors: Chen Wang, Kiernan Deangelis, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Pryseley Nkouibert Assam, Eric Bourne, Shaila Ballal, Paul DorinskyAbstract:This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12–24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint. In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference − 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated. Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD. ClinicalTrials.gov NCT02497001.
-
Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD.
International journal of chronic obstructive pulmonary disease, 2019Co-Authors: Masakazu Ichinose, Gary T. Ferguson, Yasushi Fukushima, Yoshikazu Inoue, Osamu Hataji, Klaus F. Rabe, Nobuya Hayashi, Hiroshi Okada, Mami Takikawa, Eric BourneAbstract:Background Budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) is a triple fixed-dose combination for COPD. The long-term safety of triple therapy for COPD has not been investigated in Japanese patients. In this 28-week extension study (NCT03262012), we investigated the long-term safety and tolerability of BGF MDI in Japanese patients with moderate-to-very severe COPD who completed the 24-week Phase III randomized, double-blind, multicenter KRONOS study (NCT02497001). Materials and methods Patients randomized to BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice-daily in KRONOS continued treatment for up to 28 additional weeks. Safety was evaluated over 52 weeks via adverse event (AE) monitoring, electrocardiograms, clinical laboratory testing, and vital sign measurements. Results The safety population included 416 patients who received BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Treatment-emergent AE (TEAE) rates were similar across treatment groups (range: 82.6-82.9%). The most frequent TEAEs overall were nasopharyngitis (32.2%) and bronchitis (9.9%). The incidence of major adverse cardiovascular events was low across groups (range: 0.0-2.9%). Over 52 weeks, the incidence of confirmed pneumonia was 9.4% (BGF MDI), 3.6% (GFF MDI), 5.7% (BFF MDI), and 2.9% (BUD/FORM DPI); in the 28-week extension period, rates were comparable across groups (range: 2.9-5.7%). Six deaths were reported (0.7-2.2% per group); none were considered treatment-related. No clinically meaningful trends were observed in electrocardiograms, laboratory parameters, or vital signs over time in any of the treatment groups. Conclusion All treatments were well tolerated over 52 weeks, and the safety profile of BGF MDI was generally comparable to dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) and inhaled corticosteroid (ICS)/LABA therapies. These findings support the long-term tolerability of BGF MDI in Japanese patients with COPD.
Edward Kerwin - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacokinetics of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD.
Pulmonary pharmacology & therapeutics, 2019Co-Authors: Leonard J. Dunn, Kiernan Deangelis, Edward Kerwin, Patrick Darken, Michael Gillen, Paul DorinskyAbstract:Abstract Background Budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, is a triple fixed-dose combination in late-stage clinical development for chronic obstructive pulmonary disease (COPD). Methods We conducted two studies to characterize the pharmacokinetic (PK) profile of BGF MDI in patients with COPD: (i) a phase I, open-label, single and chronic (7-day) dosing study (NCT03250182) with one treatment arm (BGF MDI 320/18/9.6 μg); and (ii) a PK sub-study of KRONOS (NCT02497001), a phase III, randomized, double-blind study in which patients received 24 weeks’ treatment with BGF MDI 320/18/9.6 μg, glycopyrrolate/Formoterol Fumarate (GFF) MDI 18/9.6 μg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 μg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 320/9 μg. PK parameters in both studies included maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from 0 to 12h (AUC0–12). Results In the phase I PK study (30 patients), budesonide and glycopyrronium Cmax were comparable after single and chronic dosing of BGF MDI (accumulation ratio [RAC] 95% and 107%, respectively) whereas Cmax for Formoterol was slightly higher after chronic dosing (RAC 116%). AUC0–12 for budesonide, glycopyrronium, and Formoterol were higher following chronic versus single dosing, with an RAC of 126%, 179%, and 143%, respectively. After 7 days’ dosing, AUC0–12 and Cmax for all three components of BGF MDI were similar to those in the KRONOS PK sub-study (202 patients) at Week 24. In the latter sub-study, Cmax and AUC0–12 at Week 24 were generally comparable across treatments for budesonide (geometric mean ratios [GMR] of 96%–109% for BGF MDI vs BFF MDI or BUD/FORM DPI), glycopyrronium (GMR of 88%–100% for BGF MDI vs GFF MDI), and Formoterol (GMR of 80%–113% for BGF MDI vs GFF MDI or BFF MDI). Conclusions Steady-state PK parameters of budesonide, glycopyrronium, and Formoterol were similar after 7 days’ dosing in the phase I PK study and after 24 weeks in the KRONOS PK sub-study. Systemic exposure to budesonide, glycopyrronium, and Formoterol was generally comparable across treatments in the KRONOS PK sub-study, suggesting no meaningful drug–drug or within-formulation PK interactions.
-
Bone and ocular safety of budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler in COPD: a 52-week randomized study
Respiratory research, 2019Co-Authors: Edward Kerwin, Kiernan Deangelis, Gary T. Ferguson, Paul DorinskyAbstract:Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/Formoterol Fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/Formoterol Fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed. In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02–0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24. In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings. ClinicalTrials.gov NCT02536508. Registered 27 August 2015.
-
bone and ocular safety of budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler in copd a 52 week randomized study
Respiratory Research, 2019Co-Authors: Edward Kerwin, Kiernan Deangelis, Gary T. Ferguson, Paul DorinskyAbstract:Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/Formoterol Fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/Formoterol Fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed. In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02–0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24. In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings. ClinicalTrials.gov NCT02536508. Registered 27 August 2015.
-
Dual bronchodilator therapy with aclidinium bromide/Formoterol Fumarate for chronic obstructive pulmonary disease
Expert review of respiratory medicine, 2015Co-Authors: Tony D’urzo, James F. Donohue, David Price, Marc Miravitlles, Edward KerwinAbstract: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.
-
dual bronchodilator therapy with aclidinium bromide Formoterol Fumarate for chronic obstructive pulmonary disease
Expert Review of Respiratory Medicine, 2015Co-Authors: Tony Durzo, David Price, James F. Donohue, Marc Miravitlles, Edward KerwinAbstract: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.
Colin Reisner - One of the best experts on this subject based on the ideXlab platform.
-
budesonide glycopyrrolate Formoterol Fumarate metered dose inhaler improves exacerbation outcomes in patients with copd without a recent exacerbation history a subgroup analysis of kronos
International Journal of Chronic Obstructive Pulmonary Disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and Methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.
International journal of chronic obstructive pulmonary disease, 2021Co-Authors: Fernando J Martinez, Paul Dorinsky, Gary T. Ferguson, Eric Bourne, Shaila Ballal, Patrick Darken, Magnus Aurivillius, Colin ReisnerAbstract:Purpose In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/Formoterol Fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study. Patients and methods Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/Formoterol Fumarate (BFF) MDI 320/9.6 µg, or budesonide/Formoterol Fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily. Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study. Results Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study. BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups. The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI. In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results. The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count. Conclusion In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations.
-
pharmacokinetics of co suspension delivery technology budesonide glycopyrronium Formoterol Fumarate dihydrate bgf mdi and budesonide Formoterol Fumarate dihydrate bff mdi fixed dose combinations compared with an active control a phase 1 randomized si
Clinical pharmacology in drug development, 2019Co-Authors: Andrea Maes, Paolo Depetrillo, Shahid Siddiqui, Colin Reisner, Paul DorinskyAbstract:This randomized, phase 1, single-dose, crossover study (NCT02189304) compared the 12-hour pharmacokinetic (PK) and safety profiles of budesonide/glycopyrronium/Formoterol Fumarate dihydrate metered dose inhaler (BGF MDI) 320/14.4/10 μg and budesonide/Formoterol Fumarate dihydrate (BFF) MDI 320/10 μg (both formulated using innovative co-suspension delivery technology) to an active comparator (budesonide/Formoterol Fumarate dihydrate dry powder inhaler [BUD/FORM DPI] 320/9-μg delivered dose) in healthy adults. The potential for PK interaction between glycopyrronium and budesonide/Formoterol within BGF MDI was assessed. Of 72 subjects randomized, 59 completed treatment. Systemic budesonide exposure (primary objective) based on area under the plasma drug concentration-time curve 0-12 hours (AUC0-12 ; % coefficient of variation) was 1598.38 (49.7), 1657.09 (50.4), and 1276.75 (70.4) pg·h/mL for BGF MDI, BFF MDI, and BUD/FORM DPI, respectively; and Formoterol exposure (AUC0-12 [% coefficient of variation]) was 39.16 (45.9), 39.53 (40.5), and 23.24 (59.2) pg·h/mL, respectively. BGF MDI and BFF MDI were bioequivalent for budesonide and Formoterol. All treatments were well tolerated. While systemic exposure to budesonide and Formoterol was higher for BGF MDI and BFF MDI than for BUD/FORM DPI, there were no appreciable differences in the incidence of pharmacologically predictable adverse events. This, coupled with the absence of PK interactions, suggests the BGF MDI safety profile will be comparable to BUD/FORM DPI.
-
Pharmacokinetics of Co-Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed-Dose Combinations Compared With an Active Control: A Phase 1, Randomi
Clinical pharmacology in drug development, 2018Co-Authors: Andrea Maes, Paolo Depetrillo, Shahid Siddiqui, Colin Reisner, Paul DorinskyAbstract:This randomized, phase 1, single-dose, crossover study (NCT02189304) compared the 12-hour pharmacokinetic (PK) and safety profiles of budesonide/glycopyrronium/Formoterol Fumarate dihydrate metered dose inhaler (BGF MDI) 320/14.4/10 μg and budesonide/Formoterol Fumarate dihydrate (BFF) MDI 320/10 μg (both formulated using innovative co-suspension delivery technology) to an active comparator (budesonide/Formoterol Fumarate dihydrate dry powder inhaler [BUD/FORM DPI] 320/9-μg delivered dose) in healthy adults. The potential for PK interaction between glycopyrronium and budesonide/Formoterol within BGF MDI was assessed. Of 72 subjects randomized, 59 completed treatment. Systemic budesonide exposure (primary objective) based on area under the plasma drug concentration-time curve 0-12 hours (AUC0-12 ; % coefficient of variation) was 1598.38 (49.7), 1657.09 (50.4), and 1276.75 (70.4) pg·h/mL for BGF MDI, BFF MDI, and BUD/FORM DPI, respectively; and Formoterol exposure (AUC0-12 [% coefficient of variation]) was 39.16 (45.9), 39.53 (40.5), and 23.24 (59.2) pg·h/mL, respectively. BGF MDI and BFF MDI were bioequivalent for budesonide and Formoterol. All treatments were well tolerated. While systemic exposure to budesonide and Formoterol was higher for BGF MDI and BFF MDI than for BUD/FORM DPI, there were no appreciable differences in the incidence of pharmacologically predictable adverse events. This, coupled with the absence of PK interactions, suggests the BGF MDI safety profile will be comparable to BUD/FORM DPI.
-
the pharmacokinetics of three doses of budesonide glycopyrronium Formoterol Fumarate dihydrate metered dose inhaler compared with active controls a phase i randomized single dose crossover study in healthy adults
Pulmonary Pharmacology & Therapeutics, 2018Co-Authors: Patrick Darken, Colin Reisner, Paolo Depetrillo, Earl St Rose, Paul DorinskyAbstract:The budesonide/glycopyrronium/Formoterol Fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14.4/10 μg [equivalent to budesonide/glycopyrrolate/Formoterol Fumarate 320/18/9.6 μg], 160/14.4/10 μg and 80/14.4/10 μg), two doses of a budesonide/Formoterol Fumarate dihydrate fixed-dose combination (BUD/FORM MDI 320/9 μg and 160/9 μg; not using co-suspension delivery technology) and a glycopyrronium/Formoterol Fumarate dihydrate co-suspension delivery technology MDI (GFF MDI 14.4/10 μg) in healthy volunteers (18-45 years of age). PK parameters included area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), AUC up to the last measurable concentration (AUC0-t), maximum plasma concentration (Cmax) and time to maximum plasma concentration (tmax). Safety was monitored throughout the study. Of 84 subjects randomized, 76 completed the study. BGF MDI 320/14.4/10 μg was bioequivalent to BUD/FORM MDI 320/9 μg for budesonide for Cmax, AUC0-12 and AUC0-t (primary objective). Dose proportionality was observed for the budesonide component between BGF MDI 80/14.4/10 μg and BGF MDI 160/14.4/10 μg, and between BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg. Systemic exposure to glycopyrronium and Formoterol after BGF MDI 320/14.4/10 μg treatment was similar to GFF MDI 14.4/10 μg. The rate of adverse events was 3.7-17.9% across treatments without any serious adverse events. In conclusion, BGF MDI 320/14.4/10 μg had a similar budesonide PK profile to BUD/FORM MDI 320/9 μg. No PK drug-drug interactions were observed when budesonide was added to glycopyrronium and Formoterol Fumarate dihydrate. These data support the use of budesonide 320 μg and 160 μg in future clinical trials of BGF MDI in COPD.