The Experts below are selected from a list of 6636 Experts worldwide ranked by ideXlab platform

Paul Dorinsky - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of budesonide/glycopyrronium/formoterol metered dose Inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts
    'Springer Science and Business Media LLC', 2021
    Co-Authors: Shigeo Muro, Patrick Darken, Hisatoshi Sugiura, Paul Dorinsky
    Abstract:

    Abstract Background In the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose Inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied. Methods KRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere Inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder Inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported. Results Of 1896 patients analyzed, 948 (50%) were non-reversible and had EOS 

  • pulmonary deposition of budesonide glycopyrronium formoterol fumarate dihydrate metered dose Inhaler formulated using co suspension delivery technology in healthy male subjects
    European Journal of Pharmaceutical Sciences, 2020
    Co-Authors: Samuel Israel, Ashish Kumar, Kiernan Deangelis, Magnus Aurivillius, Paul Dorinsky, Nicolas Roche, Omar S Usmani
    Abstract:

    Abstract This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose Inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 μg per actuation) radiolabelled with 99mTc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.

  • late breaking abstract copd exacerbation benefits relative to pneumonia risk with budesonide glycopyrronium formoterol metered dose Inhaler analyses from ethos
    European Respiratory Journal, 2020
    Co-Authors: Klaus F Rabe, Gary T. Ferguson, Jadwiga A. Wedzicha, Magnus Aurivillius, Colin Reisner, Fernando J Martinez, Dave Singh, Martin Jenkins, Paul Dorinsky
    Abstract:

    Background: In the Phase III, 52-week ETHOS study (NCT02465567), budesonide/glycopyrronium/formoterol metered dose Inhaler (BGF MDI) fixed-dose combination significantly reduced exacerbations vs dual therapies. However, use of inhaled corticosteroids (ICS) may also increase pneumonia risk. Objective: To quantify exacerbation benefits relative to pneumonia risk (expressed as numbers needed to treat [NNT] and numbers needed to harm [NNH], respectively) in ETHOS. Methods: Patients with moderate-to-very severe COPD and ≥1 moderate/severe exacerbation in the prior year received BGF MDI 320/14.4/10 μg or 160/14.4/10 μg, glycopyrronium/formoterol (GFF) MDI 14.4/10 μg or budesonide/formoterol (BFF) MDI 320/10 μg twice-daily via a single Aerosphere Inhaler. Exacerbation and pneumonia rates were used to calculate NNT and NNH. Results: BGF MDI 320 µg reduced exacerbation rates vs GFF MDI (NNT=3 [95% CI 3, 5]) and vs BFF MDI (NNT=7 [95% CI 4, 18]), (mITT, N=8509). Pneumonia rates across treatments were 0.02–0.05 per patient year, and were lower for BGF MDI than BFF MDI; for BGF MDI 320 μg vs GFF MDI, NNH=58 (95% CI 29, 152; Table). Conclusions: In patients with moderate/very severe COPD, BGF MDI 320 µg reduced exacerbation risk vs both dual therapies. For the ICS component, the NNH (BGF MDI 320 μg vs GFF MDI) suggests a low pneumonia risk for BGF MDI relative to its benefits on exacerbations.

  • efficacy and safety of two doses of budesonide formoterol fumarate metered dose Inhaler in copd
    ERJ Open Research, 2020
    Co-Authors: Nicola A Hanania, Jack Nyberg, Elizabeth A Duncan, Fernando J Martinez, Alberto Papi, Antonio Anzueto, K Rossman, C Cappelletti, Paul Dorinsky
    Abstract:

    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, 2020
    Co-Authors: Chen Wang, Kiernan Deangelis, Ting Yang, Jian Kang, Rongchang Chen, Li Zhao, Pryseley Nkouibert Assam, Eric Bourne, Shaila Ballal, Paul Dorinsky
    Abstract:

    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.

Mitchell Goldman - One of the best experts on this subject based on the ideXlab platform.

  • comparison of patient reported outcomes during treatment with adjustable and fixed dose budesonide formoterol pressurized metered dose Inhaler versus fixed dose fluticasone propionate salmeterol dry powder Inhaler in patients with asthma
    Journal of Asthma, 2010
    Co-Authors: Richard D Oconnor, Paula Martin, Bhash Parasuraman, Donald L Patrick, Mitchell Goldman
    Abstract:

    Objective. Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized Metered-Dose Inhaler with fixed-dose fluticasone propionate/salmeterol dry powder Inhaler regimens on patient-reported outcomes in patients aged ≥18 years with moderate to severe asthma. Methods. In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 μg × 2 inhalations (320/9 μg) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 μg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 μg twice daily to 320/9 μg once daily or 640/18 μg twice daily). Results. Mean improveme...

  • comparison of adjustable and fixed dose budesonide formoterol pressurized metered dose Inhaler and fixed dose fluticasone propionate salmeterol dry powder Inhaler in asthma patients
    The Journal of Allergy and Clinical Immunology, 2008
    Co-Authors: William W Busse, Paula Martin, Bhash Parasuraman, Shailen Shah, Laura Somerville, Mitchell Goldman
    Abstract:

    Background The adjustable-dose budesonide/formoterol dry powder Inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. Objective We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized Metered-Dose Inhaler versus the fixed-dose budesonide/formoterol pressurized Metered-Dose Inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. Methods This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 μg × 2 inhalations [320/9 μg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 μg × 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 μg] twice daily to 2 inhalations [320/9 μg] once daily or 4 inhalations [640/18 μg] twice daily) for 6 months (treatment period 2). Results There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P Conclusions Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

William W Busse - One of the best experts on this subject based on the ideXlab platform.

  • comparison of ipratropium bromide and albuterol sulfate chlorofluorocarbon metered dose Inhaler and albuterol hydrofluoroalkane metered dose Inhaler in a crossover trial in patients with moderate to severe asthma
    The Journal of Allergy and Clinical Immunology, 2011
    Co-Authors: Eugene R Bleecker, William W Busse, James F Donohue, S Garfinkel, T Lystig, Raymond C Manuel, Rozsa Schlenkerherceg, Robert A Wise
    Abstract:

    S U N D A Y 309 Comparison of Ipratropium Bromide and Albuterol Sulfate Chlorofluorocarbon Metered-Dose Inhaler and Albuterol Hydrofluoroalkane Metered-Dose Inhaler in a Crossover Trial in Patients with Moderate-to-Severe Asthma E. R. Bleecker, W. W. Busse, J. F. Donohue, S. Garfinkel, T. Lystig, R. C. Manuel, R. Schlenker-Herceg, R. A. Wise; Wake Forest University Center of Genomics and Personalized Medicine, Winston-Salem, NC, University of Wisconsin, Madison, WI, University of North Carolina, Chapel Hill, NC, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Compare the efficacy and safety of Combivent CFC MDI (CVT) to albuterol HFA MDI (ALB) in a multicenter, randomized study including a 4-week, 2-way crossover double-blind treatment phase. We hypothesized that albuterol and ipratropium bromide produce better bronchodilation than albuterol alone in patients with moderate-to-severe asthma. METHODS: Patients were randomized to two treatment sequences: CVT/ ALB or ALB/CVT. OnDays 1 and 29 of each period, serial spirometry was performed after clinic administration of study drug. Between clinic visits patients used studymedication ‘‘as needed’’ for relief. The co-primary endpoints were FEV1 area under the curve (AUC0-6h) above test-day baseline and peak FEV1 response after 4 weeks. Treatment effects were analyzed using repeated measures mixed-effects models. RESULTS: 226 patients were randomized: age 47 years, 43% men, postbronchodilator FEV1 2.56 L (78% predicted), and Asthma Control Questionnaire score 2.5. Estimated changes (mL) in peak FEV1 were 357 for ALB and 434 for CVT (delta577, p<0.0001). Estimated changes (mL) in FEV1 AUC0-6h were 167 for ALB and 252 for CVT (delta585, p<0.0001). Treatment differences favoring CVT were observed at every post-dose timepoint, ranging from 50-115 mL (6h, 4h) [all p<0.01]. 68 patients (29.2%) experienced adverse events. These were generally balanced between groups. More patients reported ‘‘cough’’ related to study drug CVT (11) compared to ALB (1). More asthma exacerbations were reported in CVT (6) than in ALB group (3); none of these were serious. CONCLUSIONS: CVT was safely used to provide improved acute bronchodilation over albuterol alone, after four weeks of ‘‘as-needed’’ use for symptom relief.

  • comparison of adjustable and fixed dose budesonide formoterol pressurized metered dose Inhaler and fixed dose fluticasone propionate salmeterol dry powder Inhaler in asthma patients
    The Journal of Allergy and Clinical Immunology, 2008
    Co-Authors: William W Busse, Paula Martin, Bhash Parasuraman, Shailen Shah, Laura Somerville, Mitchell Goldman
    Abstract:

    Background The adjustable-dose budesonide/formoterol dry powder Inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. Objective We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized Metered-Dose Inhaler versus the fixed-dose budesonide/formoterol pressurized Metered-Dose Inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. Methods This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 μg × 2 inhalations [320/9 μg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 μg × 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 μg] twice daily to 2 inhalations [320/9 μg] once daily or 4 inhalations [640/18 μg] twice daily) for 6 months (treatment period 2). Results There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P Conclusions Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

Bhash Parasuraman - One of the best experts on this subject based on the ideXlab platform.

  • comparison of patient reported outcomes during treatment with adjustable and fixed dose budesonide formoterol pressurized metered dose Inhaler versus fixed dose fluticasone propionate salmeterol dry powder Inhaler in patients with asthma
    Journal of Asthma, 2010
    Co-Authors: Richard D Oconnor, Paula Martin, Bhash Parasuraman, Donald L Patrick, Mitchell Goldman
    Abstract:

    Objective. Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized Metered-Dose Inhaler with fixed-dose fluticasone propionate/salmeterol dry powder Inhaler regimens on patient-reported outcomes in patients aged ≥18 years with moderate to severe asthma. Methods. In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 μg × 2 inhalations (320/9 μg) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 μg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 μg twice daily to 320/9 μg once daily or 640/18 μg twice daily). Results. Mean improveme...

  • comparison of adjustable and fixed dose budesonide formoterol pressurized metered dose Inhaler and fixed dose fluticasone propionate salmeterol dry powder Inhaler in asthma patients
    The Journal of Allergy and Clinical Immunology, 2008
    Co-Authors: William W Busse, Paula Martin, Bhash Parasuraman, Shailen Shah, Laura Somerville, Mitchell Goldman
    Abstract:

    Background The adjustable-dose budesonide/formoterol dry powder Inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. Objective We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized Metered-Dose Inhaler versus the fixed-dose budesonide/formoterol pressurized Metered-Dose Inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. Methods This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 μg × 2 inhalations [320/9 μg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 μg × 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 μg] twice daily to 2 inhalations [320/9 μg] once daily or 4 inhalations [640/18 μg] twice daily) for 6 months (treatment period 2). Results There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P Conclusions Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

  • the effect of budesonide and formoterol in one pressurized metered dose Inhaler on patient reported outcomes in adults with mild to moderate persistent asthma
    Current Medical Research and Opinion, 2008
    Co-Authors: Kevin R Murphy, Bhash Parasuraman, Christopher J. Miller, Harold S Nelson, Robert Boggs, L Odowd
    Abstract:

    ABSTRACTObjective: To determine the effects of budesonide and formoterol administered via one pressurized Metered-Dose Inhaler (budesonide/formoterol pMDI) on patient-reported outcomes (PROs) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma.Research design and methods: A 12-week, random­ized, double-blind, double-dummy, placebo-controlled, multicenter study was conducted in 480 patients aged ≥ 12 years with mild-to-moderate persistent asthma. After a 2-week run-in period during which current asthma therapy was discontinued, patients were randomized to receive two inhalations twice daily of budesonide/formo­terol pMDI 80/4.5 μg (160/9 μg), budesonide pMDI 80 μg (160 μg), formoterol via dry powder Inhaler (DPI) 4.5 μg (9 μg), or placebo.Main outcome measures: Analyses included a subpopulation of 405 patients aged ≥ 18 years. PROs included the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), the Medical Outcomes Study (MOS) Sleep Scale, the Pa...

Colin Reisner - One of the best experts on this subject based on the ideXlab platform.

  • late breaking abstract copd exacerbation benefits relative to pneumonia risk with budesonide glycopyrronium formoterol metered dose Inhaler analyses from ethos
    European Respiratory Journal, 2020
    Co-Authors: Klaus F Rabe, Gary T. Ferguson, Jadwiga A. Wedzicha, Magnus Aurivillius, Colin Reisner, Fernando J Martinez, Dave Singh, Martin Jenkins, Paul Dorinsky
    Abstract:

    Background: In the Phase III, 52-week ETHOS study (NCT02465567), budesonide/glycopyrronium/formoterol metered dose Inhaler (BGF MDI) fixed-dose combination significantly reduced exacerbations vs dual therapies. However, use of inhaled corticosteroids (ICS) may also increase pneumonia risk. Objective: To quantify exacerbation benefits relative to pneumonia risk (expressed as numbers needed to treat [NNT] and numbers needed to harm [NNH], respectively) in ETHOS. Methods: Patients with moderate-to-very severe COPD and ≥1 moderate/severe exacerbation in the prior year received BGF MDI 320/14.4/10 μg or 160/14.4/10 μg, glycopyrronium/formoterol (GFF) MDI 14.4/10 μg or budesonide/formoterol (BFF) MDI 320/10 μg twice-daily via a single Aerosphere Inhaler. Exacerbation and pneumonia rates were used to calculate NNT and NNH. Results: BGF MDI 320 µg reduced exacerbation rates vs GFF MDI (NNT=3 [95% CI 3, 5]) and vs BFF MDI (NNT=7 [95% CI 4, 18]), (mITT, N=8509). Pneumonia rates across treatments were 0.02–0.05 per patient year, and were lower for BGF MDI than BFF MDI; for BGF MDI 320 μg vs GFF MDI, NNH=58 (95% CI 29, 152; Table). Conclusions: In patients with moderate/very severe COPD, BGF MDI 320 µg reduced exacerbation risk vs both dual therapies. For the ICS component, the NNH (BGF MDI 320 μg vs GFF MDI) suggests a low pneumonia risk for BGF MDI relative to its benefits on exacerbations.

  • safety and pharmacokinetics of budesonide glycopyrronium formoterol fumarate dihydrate metered dose Inhaler bgf mdi in healthy adult subjects of japanese descent
    Pulmonary Pharmacology & Therapeutics, 2018
    Co-Authors: Paul Dorinsky, Andrea Maes, Shahid Siddiqui, Paolo Depetrillo, Colin Reisner
    Abstract:

    Abstract Introduction BGF MDI, a budesonide, glycopyrronium, and formoterol fumarate dihydrate triple fixed-dose combination metered dose Inhaler formulated using co-suspension delivery technology, is currently in Phase III global development for chronic obstructive pulmonary disease. Methods This was a Phase I, randomized, double-blind, placebo-controlled, ascending-dose, crossover study to assess the safety and pharmacokinetic profiles of two doses of BGF MDI in healthy adult subjects of Japanese descent (NCT02197975). Safety assessments included monitoring for adverse events (AEs). Pharmacokinetic parameters were assessed following a single dose and 7-days chronic dosing with BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg. Results Twenty subjects were randomized and included in the safety and pharmacokinetic populations; mean age 29.7 years; 65% male; and mean body mass index of 21.9 kg/m2. The incidences of treatment-emergent AEs (TEAEs) were similar between treatments. All the TEAEs were mild to moderate in severity. Budesonide area under the plasma concentration-time curve from 0 to 12 h (AUC0–12) and maximum observed plasma concentration (Cmax) values were approximately double for the higher dose of BGF MDI compared with the lower dose on Day 1 and also following chronic dosing on Day 8. Glycopyrronium and formoterol AUC0–12 and Cmax values on Day 8 were comparable between the two doses of BGF MDI. Discussion Both doses of BGF MDI were well tolerated in healthy subjects of Japanese descent and the systemic exposure to budesonide was dose proportional for BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg. The safety and pharmacokinetics for BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg in Japanese subjects were comparable to data from previous studies in Western populations, which suggests that the safety and efficacy profile of BGF MDI should be similar in Western and Japanese subjects.

  • efficacy safety and dose response of glycopyrronium administered by metered dose Inhaler using co suspension delivery technology in subjects with intermittent or mild to moderate persistent asthma a randomized controlled trial
    Respiratory Medicine, 2018
    Co-Authors: Edward Kerwin, Shahid Siddiqui, Andrew Wachtel, Lawrence Sher, Jack Nyberg, Patrick Darken, Elizabeth A Duncan, Colin Reisner, Paul Dorinsky
    Abstract:

    Abstract Objectives This randomized, double-blind, placebo-controlled, cross-over, Phase II dose-ranging study investigated the efficacy and safety of GP MDI (glycopyrronium administered by metered dose Inhaler formulated using co-suspension delivery technology) compared with an open-label active comparator, salmeterol dry powder Inhaler (SAL DPI), in subjects with intermittent or mild-to-moderate persistent asthma. Methods Subjects were randomized to receive five of seven treatments (GP MDI 28.8, 14.4, 7.2, 3.6, and 1.9 μg, placebo MDI, and SAL DPI 50 μg), each for a 14-day period. The primary endpoint was peak change from baseline in forced expiratory volume in 1 s (FEV1) on Day 15. Secondary endpoints included additional lung function parameters and symptoms (Asthma Control Questionnaire-5). Safety was monitored throughout. Results Of 248 subjects randomized, 211 completed the study. All doses of GP MDI resulted in significant improvements in the primary endpoint compared with placebo MDI in a dose-ordered fashion (range 85–155 mL, p  Conclusions The results of this study suggest that GP MDI could offer an important treatment option for maintenance therapy of asthma, and warrants further investigation in Phase III clinical trials.

  • cardiovascular safety profile of a fixed dose combination of glycopyrrolate and formoterol fumarate delivered via metered dose Inhaler using co suspension delivery technology
    Pulmonary Pharmacology & Therapeutics, 2018
    Co-Authors: Gary T. Ferguson, Andrea Maes, Colin Reisner, James Pearle, Paolo Depetrillo, Ubaldo J Martin
    Abstract:

    Abstract Background Glycopyrrolate/formoterol fumarate (GFF) metered dose Inhaler (MDI) is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA), glycopyrrolate (GP), and the long-acting β 2 -agonist (LABA), formoterol fumarate (FF), delivered via metered dose Inhaler using innovative co-suspension delivery technology. Here we report the results of two studies that examined the cardiovascular safety of GFF MDI. Methods The thorough QT (TQT) study was a Phase I, randomized, double-blind, single-dose, crossover study to assess GFF MDI 18/9.6 (Bevespi Aerosphere® ), GFF MDI 144/38.4 and GP MDI 144 μg, compared with placebo MDI and open-label moxifloxacin 400 mg (active control) in healthy volunteers (PT003009). The cardiovascular safety study in patients with chronic obstructive pulmonary disease (COPD) was a Phase IIb, randomized, multicenter, double-blind, 14-day dosing, parallel-group study to evaluate GFF MDI 36/9.6, GP MDI 36 and FF MDI 9.6 μg compared with open-label FF dry powder Inhaler (DPI; Foradil ® Aerolizer®) 12 μg, in patients with moderate-to-severe COPD (PT003003 [NCT01349803]). Results Seventy healthy volunteers were randomized in the TQT study. GFF MDI 144/38.4, GFF MDI 18/9.6 and GP MDI 144 μg all met the confidence interval-based criteria for negative QT prolongation potential. In the study in patients with COPD, 237 subjects were randomized and treated. GFF MDI 36/9.6, GP MDI 36, and FF MDI 9.6 μg did not result in clinically meaningful changes from baseline in 24-h mean heart rate at Day 14 (primary endpoint) or in any of the other Holter monitoring endpoints at Day 14, compared with FF DPI 12 μg. Conclusions No clinically significant effects on cardiovascular safety occurred at therapeutic or supratherapeutic doses of GFF MDI, apart from a small and transient increase in heart rate following supratherapeutic dose of GFF MDI 144/38.4 μg. Furthermore, there were no unexpected safety findings reported in either healthy volunteers or patients with COPD.

  • baseline symptom score impact on benefits of glycopyrrolate formoterol metered dose Inhaler in copd
    Chest, 2017
    Co-Authors: Fernando J Martinez, Gary T. Ferguson, Chad Orevillo, Ubaldo J Martin, Patrick Darken, Leonardo M Fabbri, Colin Reisner
    Abstract:

    Background The clinical severity of COPD is currently categorized by symptom burden and exacerbation risk. Previous 24-week phase III trials (NCT01854645 and NCT01854658) that demonstrated better improvement of lung function with glycopyrrolate/formoterol fumarate (GFF) metered dose Inhaler (MDI) (an MDI fixed-dose of GFF 18/9.6 μg) over individual monocomponent MDIs included a cross-section of patients with moderate to very severe airflow limitation and a broad range of COPD symptoms. Methods These post hoc analyses of pooled data investigated whether baseline symptom burden, assessed using the COPD Assessment Test (CAT) score, impacted GFF MDI-associated improvements in lung function, health status, rescue medication use, and exacerbation risk. Results In 3,699 patients, improvement in FEV1 at week 24 between the GFF MDI and monocomponent MDIs and a placebo MDI was similar in magnitude regardless of baseline CAT score. In contrast, the magnitude of mean difference in the St. George's Respiratory Questionnaire total score for GFF MDI vs monocomponent MDIs and the placebo MDI increased with increasing baseline CAT scores. Likewise, reduced rescue medication use and lower exacerbation risk were more pronounced in GFF MDI groups with a higher baseline symptom burden. Conclusions Beneficial effects of GFF MDI on health status, rescue medication use, and exacerbation risk in symptomatic patients with COPD increased as a function of baseline symptom burden, whereas lung function benefits were independent. These data suggest a greater clinical benefit from dual bronchodilators in symptomatic patients than in patients without symptoms. Trial Registry ClinicalTrials.gov; No.: NCT01854645 and NCT01854658; URL: www.clinicaltrials.gov.