18 results on '"Donohue, James"'
Search Results
2. Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)
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Donohue, James F., Kerwin, Edward, Sethi, Sanjay, Haumann, Brett, Pendyala, Srikanth, Dean, Lorna, Barnes, Chris N., Moran, Edmund J., and Crater, Glenn
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- 2019
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3. Weighing the evidence for pharmacological treatment interventions in mild COPD; a narrative perspective
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Singh, Dave, D’Urzo, Anthony D., Donohue, James F., and Kerwin, Edward M.
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- 2019
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4. Dose selection for glycopyrrolate/eFlow® phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies
- Author
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Donohue, James F
- Abstract
Background Long-acting muscarinic antagonists (LAMAs) are recommended for the treatment of chronic obstructive pulmonary disease (COPD). Glycopyrrolate/eFlow® is an investigational drug–device combination of the LAMA glycopyrrolate administered by an eFlow® Closed System (eFlow® CS) nebulizer. The GOLDEN 2 (NCT01706536) and GOLDEN 6 (NCT02038829) Phase II, multicenter studies were conducted to inform dose selection for the GOLDEN Phase III clinical trials. Bronchodilator responses and safety assessments supported dose selection. Methods Subjects with moderate-to-severe COPD were randomized into 28-day parallel-group (GOLDEN 2) or 7-day crossover (GOLDEN 6) studies and received placebo, glycopyrrolate (3, 6.25, 12.5, 25, 50 or 100 μg twice daily [BID]) or aclidinium bromide 400 μg BID. The primary endpoint of both studies was change from baseline in trough forced expiratory volume in 1 s (FEV1). Safety assessments included the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events, and discontinuation due to TEAE. Lung function data collected in both studies were pooled. Results The combined GOLDEN 2 (n = 282) and GOLDEN 6 (n = 96) studies included 378 subjects. On Days 7 and 28 there were dose-ordered, statistically significant and clinically important lung function improvements in glycopyrrolate treatment groups. Specifically, on Day 7, glycopyrrolate produced >0.100 L placebo-adjusted changes from baseline in trough FEV1 (12.5 μg BID: 0.122 L; 25 μg BID: 0.123 L; 50 μg BID: 0.137 L) and FEV1 AUC0–12 (12.5 μg BID: 0.145 L; 25 μg BID: 0.178 L; 50 μg BID: 0.180 L). The improvements in lung function for the glycopyrrolate 25 and 50 μg BID doses were comparable to those with aclidinium bromide 400 μg BID (FEV1: 0.149 L; FEV1 AUC0−12: 0.172 L). Acceptable safety profiles were observed across all groups in both studies. Conclusions The efficacy and safety findings supported selection of glycopyrrolate 25 and 50 μg BID doses for the Phase III GOLDEN studies and provided preliminary evidence for the use of nebulized glycopyrrolate as a maintenance therapy for COPD.
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- 2017
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5. Comparative efficacy of long-acting bronchodilators for COPD - a network meta-analysis
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Donohue, James F
- Subjects
respiratory tract diseases - Abstract
Background Clinicians are faced with an increasingly difficult choice regarding the optimal bronchodilator for patients with chronic obstructive pulmonary disease (COPD) given the number of new treatments. The objective of this study is to evaluate the comparative efficacy of indacaterol 75/150/300 μg once daily (OD), glycopyrronium bromide 50 μg OD, tiotropium bromide 18 μg/5 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for moderate to severe COPD. Methods Forty randomized controlled trials were combined in a Bayesian network meta-analysis. Outcomes of interest were trough and post-dose forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) score and responders (≥4 points), and Transition Dyspnea Index (TDI) score and responders (≥1 point) at 6 months. Results Indacaterol was associated with a higher trough FEV1 than other active treatments (difference for indacaterol 150 μg and 300 μg versus placebo: 152 mL (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the greatest improvement in SGRQ score (difference for indacaterol 150 μg and 300 μg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)). Glycopyrronium and tiotropium 18 μg resulted in the next best estimates for both outcomes with minor differences (difference for glycopyrronium versus tiotropium for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92). Conclusion In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium, and tiotropium are expected to be the most effective bronchodilators.
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- 2013
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6. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease
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Donohue, James F
- Subjects
respiratory tract diseases - Abstract
Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1
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- 2011
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7. Dose selection for glycopyrrolate/eFlow® phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies.
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Donohue, James F., Goodin, Thomas, Tosiello, Robert, and Wheeler, Alistair
- Subjects
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OBSTRUCTIVE lung disease treatment , *GLYCOPYRROLATE , *MUSCARINIC antagonists , *DATA , *RANDOMIZED controlled trials - Abstract
Background: Long-acting muscarinic antagonists (LAMAs) are recommended for the treatment of chronic obstructive pulmonary disease (COPD). Glycopyrrolate/eFlow® is an investigational drug-device combination of the LAMA glycopyrrolate administered by an eFlow® Closed System (eFlow® CS) nebulizer. The GOLDEN 2 (NCT01706536) and GOLDEN 6 (NCT02038829) Phase II, multicenter studies were conducted to inform dose selection for the GOLDEN Phase III clinical trials. Bronchodilator responses and safety assessments supported dose selection.Methods: Subjects with moderate-to-severe COPD were randomized into 28-day parallel-group (GOLDEN 2) or 7-day crossover (GOLDEN 6) studies and received placebo, glycopyrrolate (3, 6.25, 12.5, 25, 50 or 100 μg twice daily [BID]) or aclidinium bromide 400 μg BID. The primary endpoint of both studies was change from baseline in trough forced expiratory volume in 1 s (FEV1). Safety assessments included the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events, and discontinuation due to TEAE. Lung function data collected in both studies were pooled.Results: The combined GOLDEN 2 (n = 282) and GOLDEN 6 (n = 96) studies included 378 subjects. On Days 7 and 28 there were dose-ordered, statistically significant and clinically important lung function improvements in glycopyrrolate treatment groups. Specifically, on Day 7, glycopyrrolate produced >0.100 L placebo-adjusted changes from baseline in trough FEV1 (12.5 μg BID: 0.122 L; 25 μg BID: 0.123 L; 50 μg BID: 0.137 L) and FEV1 AUC0-12 (12.5 μg BID: 0.145 L; 25 μg BID: 0.178 L; 50 μg BID: 0.180 L). The improvements in lung function for the glycopyrrolate 25 and 50 μg BID doses were comparable to those with aclidinium bromide 400 μg BID (FEV1: 0.149 L; FEV1 AUC0-12: 0.172 L). Acceptable safety profiles were observed across all groups in both studies.Conclusions: The efficacy and safety findings supported selection of glycopyrrolate 25 and 50 μg BID doses for the Phase III GOLDEN studies and provided preliminary evidence for the use of nebulized glycopyrrolate as a maintenance therapy for COPD. [ABSTRACT FROM AUTHOR]- Published
- 2017
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- View/download PDF
8. A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease.
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Reisner, Colin, Fabbri, Leonardo M., Kerwin, Edward M., Fogarty, Charles, Spangenthal, Selwyn, Rabe, Klaus F., Ferguson, Gary T., Martinez, Fernando J., Donohue, James F., Darken, Patrick, St. Rose, Earl, Orevillo, Chad, Strom, Shannon, Fischer, Tracy, Golden, Michael, and Dwivedi, Sarvajna
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OBSTRUCTIVE lung disease diagnosis ,MUSCARINIC agonists ,GLYCOPYRROLATE ,BISOPROLOL ,METERED-dose inhalers ,ADRENERGIC beta agonists ,COMBINATION drug therapy ,COMPARATIVE studies ,OBSTRUCTIVE lung diseases ,RESEARCH methodology ,MEDICAL cooperation ,PLACEBOS ,RESEARCH ,RESPIRATORY therapy equipment ,PRODUCT design ,EVALUATION research ,RANDOMIZED controlled trials ,TREATMENT effectiveness ,BLIND experiment ,SEVERITY of illness index ,MEDICAL equipment reliability ,MUSCARINIC antagonists ,INHALATION administration - Abstract
Background: Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI).Methods: This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD ( NCT01085045 ). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 7 relative to baseline FEV1. Secondary endpoints included pharmacokinetics and safety.Results: GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV1 AUC0-12 after 7 days' treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated.Conclusions: GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.Trial Registration: ClinicalTrials.gov NCT01085045 . Registered 9 March 2010. [ABSTRACT FROM AUTHOR]- Published
- 2017
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9. A retrospective study of two populations to test a simple rule for spirometry.
- Author
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Ohar, Jill A., Yawn, Barbara P., Ruppel, Gregg L., and Donohue, James F.
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LUNG disease diagnosis ,AGE distribution ,CHI-squared test ,COMPARATIVE studies ,CONFIDENCE intervals ,CORONARY disease ,DECISION making ,FAMILY medicine ,LUNG diseases ,OCCUPATIONAL health services ,PREOPERATIVE care ,PROBABILITY theory ,RESEARCH funding ,RESPIRATORY measurements ,SMOKING ,SPIROMETRY ,SURVIVAL analysis (Biometry) ,LOGISTIC regression analysis ,PREDICTIVE tests ,VITAL capacity (Respiration) ,PROPORTIONAL hazards models ,RETROSPECTIVE studies ,PATIENT selection ,RECEIVER operating characteristic curves ,DATA analysis software ,ODDS ratio ,ONE-way analysis of variance ,SYMPTOMS - Abstract
Background: Chronic lung disease is common and often under-diagnosed. Methods: To test a simple rule for conducting spirometry we reviewed spirograms from two populations, occupational medicine evaluations (OME) conducted by Saint Louis and Wake Forest Universities at 3 sites (n = 3260, mean age 64.14 years, 95 % CI 58.94-69.34, 97 % men) and conducted by Wake Forest University preop clinic (POC) at one site (n = 845, mean age 62.10 years, 95 % CI 50.46-73.74, 57 % men). This retrospective review of database information that the first author collected prospectively identified rates, types, sensitivity, specificity and positive and negative predictive value for lung function abnormalities and associated mortality rate found when conducting spirometry based on the 20/40 rule (≥20 years of smoking in those aged ≥ 40 years) in the OME population. To determine the reproducibility of the 20/40 rule for conducting spirometry, the rule was applied to the POC population. Results: A lung function abnormality was found in 74 % of the OME population and 67 % of the POC population. Sensitivity of the rule was 85 % for an obstructive pattern and 77 % for any abnormality on spirometry. Positive and negative predictive values of the rule for a spirometric abnormality were 74 and 55 %, respectively. Patients with an obstructive pattern were at greater risk of coronary heart disease (odds ratio (OR) 1.39 [confidence interval (CI) 1.00-1. 93] vs. normal) and death (hazard ratio (HR) 1.53, 95 % CI 1.20-1.84) than subjects with normal spirometry. Restricted spirometry patterns were also associated with greater risk of coronary disease (odds ratio (OR) 1.7 [CI 1.23-2.35]) and death (Hazard ratio 1.40, 95 % CI 1.08-1.72). Conclusions: Smokers (≥ 20 pack years) age ≥ 40 years are at an increased risk for lung function abnormalities and those abnormalities are associated with greater presence of coronary heart disease and increased all-cause mortality. Use of the 20/40 rule could provide a simple method to enhance selection of candidates for spirometry evaluation in the primary care setting. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial.
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Donohue, James F., Wise, Robert, Busse, William W., Garfinkel, Sandra, Zubek, Valentina B., Mo Ghafouri, Manuel, Raymond C., Schlenker-Herceg, Rozsa, Bleecker, Eugene R., and Ghafouri, Mo
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IPRATROPIUM (Drug) ,ALBUTEROL ,ASTHMA treatment ,BRONCHIAL spasm ,RANDOMIZED controlled trials ,DRUG therapy for asthma ,ADRENERGIC beta agonists ,ASTHMA ,BRONCHODILATOR agents ,COMBINATION drug therapy ,COMPARATIVE studies ,CROSSOVER trials ,DOSE-effect relationship in pharmacology ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESPIRATORY therapy equipment ,STATISTICAL sampling ,SPIROMETRY ,TIME ,EVALUATION research ,TREATMENT effectiveness ,VITAL capacity (Respiration) ,BLIND experiment ,RETROSPECTIVE studies ,INHALATION administration - Abstract
Background: Many patients with asthma require frequent rescue medication for acute symptoms despite appropriate controller therapies. Thus, determining the most effective relief regimen is important in the management of more severe asthma. This study's objective was to evaluate whether ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI) provides more effective acute relief of bronchospasm in moderate-to-severe asthma than albuterol hydrofluoroalkaline (ALB-HFA) alone after 4 weeks.Methods: In this double-blind, crossover study, patients who had been diagnosed with asthma for ≥1 year were randomized to two sequences of study medication "as needed" for symptom relief (1-7 day washout before second 4-week treatment period): CVT-MDI/ALB-HFA or ALB-HFA/CVT-MDI. On days 1 and 29 of each sequence, 6-hour serial spirometry was performed after administration of the study drug. Co-primary endpoints were FEV1 area under the curve (AUC0-6) and peak (post-dose) forced expiratory volume in 1 s (FEV1) response (change from test day baseline) after 4 weeks. The effects of "as needed" treatment with ALB-HFA/CVT-MDI were analyzed using mixed effect model repeated measures (MMRM).Results: A total of 226 patients, ≥18 years old, with inadequately controlled, moderate-to-severe asthma were randomized. The study met both co-primary endpoints demonstrating a statistically significant treatment benefit of CVT-MDI versus ALB-HFA. FEV1 AUC0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI (p <0.0001); peak FEV1 response was 357 ml for ALB-HFA, 434 ml for CVT-MDI (p <0.0001). Adverse events were comparable across groups.Conclusions: CVT-MDI significantly improved acute bronchodilation over ALB-HFA alone after 4 weeks of "as-needed" use for symptom relief, with a similar safety profile. This suggests additive bronchodilator effects of β2-agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma.Trial Registration: ClinicalTrials.gov No.: NCT00818454 ; Registered November 16, 2009. [ABSTRACT FROM AUTHOR]- Published
- 2016
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11. The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis.
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Martin, Amber L., Marvel, Jessica, Fahrbach, Kyle, Cadarette, Sarah M., Wilcox, Teresa K., and Donohue, James F.
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DISEASE exacerbation ,OBSTRUCTIVE lung diseases patients ,REGRESSION analysis ,HOSPITAL care ,LONGITUDINAL method - Abstract
Background: This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George's Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations.Methods: A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance.Results: Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant.Conclusions: The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships, results were in the expected direction with few exceptions. The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies. [ABSTRACT FROM AUTHOR]- Published
- 2016
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12. Erratum to: A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease.
- Author
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Reisner, Colin, Fabbri, Leonardo M, Kerwin, Edward M, Fogarty, Charles, Spangenthal, Selwyn, Rabe, Klaus F, Ferguson, Gary T, Martinez, Fernando J, Donohue, James F, Darken, Patrick, St Rose, Earl, Orevillo, Chad, Strom, Shannon, Fischer, Tracy, Golden, Michael, and Dwivedi, Sarvajna
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GLYCOPYRROLATE ,OBSTRUCTIVE lung disease treatment ,DRUG efficacy - Abstract
A correction is presented to the article regarding the safety and efficacy of formoterol fumarate and glycopyrrolate in patients who suffered from chronic obstructive pulmonary disease, which published online in the August 21, 2017 issue.
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- 2017
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13. Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study.
- Author
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Donohue, James F., Niewoehner, Dennis, Brooks, Jean, O'Dell, Dianne, and Church, Alison
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- *
OBSTRUCTIVE lung diseases , *MUSCARINIC antagonists , *ATRIAL arrhythmias , *SUPRAVENTRICULAR tachycardia , *RANDOMIZED controlled trials , *PLACEBOS - Abstract
Background: The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU. They are not indicated for the treatment of asthma. Methods: In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo. Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms. COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated. Results: The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%). Headache was the most common AE in each treatment group (8-11%). AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups. No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo. The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ⩾2% greater than placebo. With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ⩾1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ⩾1 exacerbation, 2.6 puffs/day). Both active treatments improved lung function versus placebo. Conclusion: UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. [ABSTRACT FROM AUTHOR]
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- 2014
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14. Comparative efficacy of long-acting bronchodilators for COPD - a network meta-analysis.
- Author
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Cope, Shannon, Donohue, James F., Jansen, Jeroen P., Kraemer, Matthias, Capkun-Niggli, Gorana, Baldwin, Michael, Buckley, Felicity, Ellis, Alexandra, and Jones, Paul
- Subjects
- *
BRONCHODILATOR agents , *OBSTRUCTIVE lung diseases , *INDACATEROL , *FORMOTEROL , *SALMETEROL , *META-analysis , *GENETICS - Abstract
Background: Clinicians are faced with an increasingly difficult choice regarding the optimal bronchodilator for patients with chronic obstructive pulmonary disease (COPD) given the number of new treatments. The objective of this study is to evaluate the comparative efficacy of indacaterol 75/150/300 μg once daily (OD), glycopyrronium bromide 50 μg OD, tiotropium bromide 18 μg/5 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for moderate to severe COPD. Methods: Forty randomized controlled trials were combined in a Bayesian network meta-analysis. Outcomes of interest were trough and post-dose forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score and responders (⩾4 points), and Transition Dyspnea Index (TDI) score and responders (⩾1 point) at 6 months. Results: Indacaterol was associated with a higher trough FEV1 than other active treatments (difference for indacaterol 150 μg and 300 μg versus placebo: 152 mL (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the greatest improvement in SGRQ score (difference for indacaterol 150 μg and 300 μg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)). Glycopyrronium and tiotropium 18 μg resulted in the next best estimates for both outcomes with minor differences (difference for glycopyrronium versus tiotropium for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92). Conclusion: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium, and tiotropium are expected to be the most effective bronchodilators. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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15. Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium.
- Author
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Kai-Michael Beeh, Beier, Jutta, and Donohue, James F.
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OBSTRUCTIVE lung diseases ,RANDOMIZED controlled trials ,BLIND experiment ,INHALERS ,DYSPNEA ,INDACATEROL - Abstract
Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias. However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers. In such cases, open-label studies can be employed instead. Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables. Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited. Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator. The clinical trial programme for indacaterol, a once-daily, long-acting β
2 -agonist, used tiotropium as a comparator either in an open-label or blinded fashion. Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies. The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias. The effect of tiotropium on subjective measures (St George's Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using openlabel tiotropium. Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding. In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is openlabel, additional efforts must be made to minimise risk of bias. If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy. [ABSTRACT FROM AUTHOR]- Published
- 2012
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16. Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis.
- Author
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Jones, Paul W., Donohue, James F., Nedelman, Jerry, Pascoe, Steve, Pinault, Gregory, and Lassen, Cheryl
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OBSTRUCTIVE lung diseases patients , *LUNG diseases , *QUESTIONNAIRES , *SEVERITY of illness index , *INDACATEROL , *DISEASE exacerbation , *PATIENTS - Abstract
Background: Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes. Methods: Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use. Results: With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes. Conclusions: These results suggest that larger improvements in FEV1 are likely to be associated with larger patientreported benefits across a range of clinical outcomes. Trial Registration: ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
17. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease.
- Author
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Jones, Paul W., Rennard, Stephen I., Agusti, Alvar, Chanez, Pascal, Magnussen, Helgo, Fabbri, Leonardo, Donohue, James F., Bateman, Eric D., Gross, Nicholas J., Lamarca, Rosa, Caracta, Cynthia, and Gil, Esther Garcia
- Subjects
BROMIDES ,DRUG efficacy ,OBSTRUCTIVE lung disease treatment ,HEALTH outcome assessment ,PLACEBOS ,OBSTRUCTIVE lung disease diagnosis ,ALKALOIDS ,BRONCHODILATOR agents ,COMPARATIVE studies ,DRUG administration ,DYSPNEA ,HEALTH status indicators ,LUNGS ,OBSTRUCTIVE lung diseases ,RESEARCH methodology ,MEDICAL cooperation ,QUALITY of life ,QUESTIONNAIRES ,RESEARCH ,RESPIRATORY therapy equipment ,TIME ,LOGISTIC regression analysis ,EVALUATION research ,RANDOMIZED controlled trials ,TREATMENT effectiveness ,VITAL capacity (Respiration) ,BLIND experiment ,SEVERITY of illness index ,MUSCARINIC antagonists ,INHALATION administration - Abstract
Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p<0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p<0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD.Trial Registration: ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II). [ABSTRACT FROM AUTHOR]- Published
- 2011
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18. Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium.
- Author
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Beeh, Kai-Michael, Beier, Jutta, and Donohue, James F
- Abstract
Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias. However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers. In such cases, open-label studies can be employed instead. Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables. Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited. Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator. The clinical trial programme for indacaterol, a once-daily, long-acting β2-agonist, used tiotropium as a comparator either in an open-label or blinded fashion. Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies. The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias. The effect of tiotropium on subjective measures (St George's Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using open-label tiotropium. Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding. In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is open-label, additional efforts must be made to minimise risk of bias. If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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