Budesonide, Formoterol Fumarate Drug Combination: A pharmaceutical preparation of budesonide and formoterol fumarate that is used as an ANTI-ASTHMATIC AGENT and for the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 56841116 |
| MeSH ID | M000605997 |
| Synonym |
|---|
| budesonide-formoterol mixt |
| formoterol-budesonide mixt |
| budesonide and formoterol fumarate dihydrate |
| formoterol / budesonide |
| inhaled budesonide and formoterol |
| budesonide/formoterol combination |
| budesonide, formoterol fumarate drug combination |
| symbicort inhalation aerosol |
| formamide, n-(2-hydroxy-5-(1-hydroxy-2-((2-(4-methoxyphenyl)-1-methylethyl)amino)ethyl)phenyl)-, (r*,r*)-(+-)-, mixted with 16,17-(butylidenebis(oxy))-11,21-dihydroxypregna-1,4-diene-3,20-dione |
| pregna-1,4-diene-3,20-dione, 16,17-(butylidenebis(oxy))-11,21-dihydroxy-, (11beta,16alpha)-, mixt with (r*,r*)-(+-)-n-(2-hydroxy-5-(1-hydroxy-2-((2-(4-methoxyphenyl)-1-methylethyl)amino)ethyl)phenyl)formamide |
| pregna-1,4-diene-3,20-dione, 16,17-(butylidenebis(oxy))-11,21-dihydroxy-, (11beta,16alpha)-, mixt with rel-n-(2-hydroxy-5-((1r)-1-hydroxy-2-(((1r)-2-(4-methoxyphenyl)-1-methylethyl)amino)ethyl)phenyl)formamide |
| 150693-37-1 |
| symbicort rapihaler |
| Q863389 |
| budesonide/formoterol |
| Excerpt | Reference | Relevance |
|---|---|---|
| " In addition, GR-GRE binding is found to be a valuable pharmacodynamic marker for steroid efficacy in clinical studies." | ( Comparison of Symbicort® versus Pulmicort® on steroid pharmacodynamic markers in asthma patients. Barnes, PJ; Essilfie-Quaye, S; Ito, K; Ito, M; Kharitonov, SA, 2011) | 0.37 |
| " The non-compartmental analysis allowed for an initial characterization of the primary pharmacokinetic (PK) parameters of the two inhaled drugs and subsequently the bioequivalence assessment of the two different dry powder inhalers." | ( On the pharmacokinetics of two inhaled budesonide/formoterol combinations in asthma patients using modeling approaches. Karalis, V; Macheras, P; Soulele, K, 2018) | 0.48 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "The objective of this research was to explore the effect of the treatment regimen of Spiriva combined with Symbicort on the immune function of non-small-cell lung cancer (NSCLC) based on computed tomography (CT) imaging features." | ( Random Walk Algorithm-Based Computer Tomography (CT) Image Segmentation Analysis Effect of Spiriva Combined with Symbicort on Immunologic Function of Non-Small-Cell Lung Cancer. Li, X; Liang, M; Liu, W; Sun, Z, 2022) | 0.72 |
| "The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone)." | ( Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma-COPD overlap syndrome. Jiang, T; Li, P; Wang, Y, 2023) | 0.91 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " For inhaled BUD, the incorporation of two parallel first-order absorption rate constants (fast and slow) for lung absorption in a two-compartment PK model emphasized the importance of pulmonary anatomical features and underlying physiological processes during model development." | ( On the pharmacokinetics of two inhaled budesonide/formoterol combinations in asthma patients using modeling approaches. Karalis, V; Macheras, P; Soulele, K, 2018) | 0.48 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " At present, inhaled corticosteroids (ICS) remain the cornerstone of asthma therapy and optimal treatment strategies must consider total daily dose and dosing frequency." | ( Managing a variable disease. Kips, J, 2002) | 0.31 |
| " Symbicort has a fast onset of effect, which may help patients feel more in control of their condition and improve adherence to their medication, and a long duration of effect that allows twice-daily or even once-daily dosing during periods of good control." | ( Symbicort Turbuhaler: a new concept in asthma management. Kuna, P; Kuprys, I, 2002) | 0.31 |
| "Adjustable maintenance dosing with budesonide/formoterol in a single inhaler (Symbicort, AstraZeneca, Lund, Sweden) may provide a convenient means of maintaining asthma control with the minimum effective medication level." | ( Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Becker, AB; Boulet, LP; Ernst, P; FitzGerald, JM; Lee, JS; McIvor, AR; Sears, MR; Smiljanic-Georgijev, NM, ) | 0.13 |
| "To compare adjustable and fixed maintenance dosing regimens of budesonide/formoterol in asthma." | ( Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Becker, AB; Boulet, LP; Ernst, P; FitzGerald, JM; Lee, JS; McIvor, AR; Sears, MR; Smiljanic-Georgijev, NM, ) | 0.13 |
| " Following a one-month run-in on budesonide/formoterol (100/6 µg or 200/6 µg metered doses, two inhalations twice daily), 995 patients were randomly assigned either to continue on this fixed dosing regimen or to receive budesonide/formoterol adjustable dosing (step down to one inhalation twice daily if symptoms were controlled or temporarily step up to four inhalations twice daily for seven or 14 days if asthma worsened)." | ( Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Becker, AB; Boulet, LP; Ernst, P; FitzGerald, JM; Lee, JS; McIvor, AR; Sears, MR; Smiljanic-Georgijev, NM, ) | 0.13 |
| "With adjustable dosing, significantly fewer patients experienced exacerbations compared with fixed dosing (4." | ( Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Becker, AB; Boulet, LP; Ernst, P; FitzGerald, JM; Lee, JS; McIvor, AR; Sears, MR; Smiljanic-Georgijev, NM, ) | 0.13 |
| "Budesonide/formoterol adjustable maintenance dosing provided more effective asthma control than fixed dosing, with a lower overall drug dose and reduced total cost." | ( Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five-month multicentre Canadian study. Becker, AB; Boulet, LP; Ernst, P; FitzGerald, JM; Lee, JS; McIvor, AR; Sears, MR; Smiljanic-Georgijev, NM, ) | 0.13 |
| "Patient-guided management of asthma using adjustable dosing of budesonide/formoterol in a single inhaler (Symbicort) was compared with fixed dosing in an open-label, multicentre, randomised study." | ( Adjustable and fixed dosing with budesonide/ formoterol via a single inhaler in asthma patients: the ASSURE study. Haughney, J; Ind, PW; Kennelly, J; Price, D; Rosen, JP, 2004) | 0.32 |
| " In order to improve adherence to therapy, the use of combined therapy with an ICS and a long-acting beta2-agonist in a single inhaler should be considered and the dosing frequency should be adjusted according to the severity of asthma symptoms." | ( Budesonide and formoterol in a single inhaler controls asthma in adolescents. Pohunek, P; Tal, A, ) | 0.13 |
| " Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals." | ( Combination therapy in asthma--fixed or variable dosing in different patients? Lötvall, J, 2004) | 0.32 |
| " The results highlight a more significant effect of inspiratory flow on variable dosage emission when using the Symbicort Turbuhaler compared with the Seretide Diskus." | ( Emitted dose estimates from Seretide Diskus and Symbicort Turbuhaler following inhalation by severe asthmatics. Assi, KH; Chrystyn, H; Pearson, SB; Tarsin, WY, 2006) | 0.33 |
| " Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity." | ( Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma. Black, PN; Creemers, JP; Kuna, P; Lindqvist, A; Nihlen, U; Vogelmeier, C; Vondra, V, 2006) | 0.33 |
| " Compared with placebo, tiotropium was additive to budesonide/formoterol after single and chronic dosing measured by FEV(1) (P < ." | ( Paradoxical trough effects of triple therapy with budesonide/formoterol and tiotropium bromide on pulmonary function outcomes in COPD. Clearie, KL; Fardon, TC; Howaniec, LJ; Lipworth, BJ; Short, PM; Vaidyanathan, S; Williamson, PA, 2010) | 0.36 |
| " The Symbicort® SMART dosing regime has been shown to reduce the number of asthma exacerbations." | ( Audit of budesonide/formoterol prescribing for asthma in community pharmacy in the U.K. Boyter, AC; Ford, NH; Zlotos, L, 2011) | 0.37 |
| "The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed." | ( Dose-response relationship of ICS/fast-onset LABA as reliever therapy in asthma. Beasley, R; Bird, G; Dunphy, H; Harper, J; Papi, A; Pavord, ID; Semprini, A; Weatherall, M, 2019) | 0.51 |
| " It also showed rapid onset of bronchodilatory effect with a dose-response relationship that allows patients to utilise it as a Single Maintenance And Reliever Therapy (SMART) regimen." | ( Comparing the efficacy and safety of formoterol/budesonide pMDI versus its mono-components and other LABA/ICS in patients with asthma. Gaur, V; Gogtay, J; Mukhopadhyay, A; Waked, M, ) | 0.13 |
| " A preference of this mode is broader versatility, due to that its straighter dose-response should allow a better adaptation to disease fluctuations, and that its rapid activity enables use as "anti-inflammatory reliever"." | ( May a different kinetic mode explain the high efficacy/safety profile of inhaled budesonide? Brattsand, R; Selroos, O, 2022) | 0.72 |
| " This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies." | ( Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management. Berend, N; Daley-Yates, P; Igea, JM; Macchia, L; Plank, M; Singh, D; Verma, M, 2023) | 0.91 |
| "We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios." | ( Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management. Berend, N; Daley-Yates, P; Igea, JM; Macchia, L; Plank, M; Singh, D; Verma, M, 2023) | 0.91 |
| " Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios." | ( Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management. Berend, N; Daley-Yates, P; Igea, JM; Macchia, L; Plank, M; Singh, D; Verma, M, 2023) | 0.91 |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 44 (22.11) | 29.6817 |
| 2010's | 96 (48.24) | 24.3611 |
| 2020's | 59 (29.65) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (63.46) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 76 (35.68%) | 5.53% |
| Reviews | 42 (19.72%) | 6.00% |
| Case Studies | 5 (2.35%) | 4.05% |
| Observational | 15 (7.04%) | 0.25% |
| Other | 75 (35.21%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Randomized, Double-Blind, Parallel-Group, 28-Week, Chronic-Dosing, Multi-Center, Extension Study to Assess the Safety and Efficacy of PT010, PT003, and PT009 in Japanese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) [NCT03262012] | Phase 3 | 416 participants (Actual) | Interventional | 2016-08-09 | Completed | ||
| A 12-week, Multicentre, Randomised, Double-blind, Double-dummy, 2-arm Parallel Group Study Comparing the Efficacy and Safety of Foster® 100/6 (Beclomethasone Dipropionate 100 µg Plus Formoterol 6 µg/Actuation), 2 Puffs b.i.d., Versus Symbicort® 200/6 (Bud [NCT01351792] | Phase 3 | 113 participants (Actual) | Interventional | 2011-09-30 | Terminated | ||
| [NCT01099722] | Phase 3 | 261 participants (Actual) | Interventional | 2010-04-30 | Completed | ||
| A Randomized, Double-blind, Placebo-controlled, Two Way Cross-over Study to Assess the Particle Deposition and Acute Effects of Formoterol and Budesonide Combination Therapy (Symbicort® Forte Turbohaler®) on the Upper Airway Dimensions in COPD Patients. [NCT01329276] | Phase 4 | 10 participants (Actual) | Interventional | 2010-06-30 | Completed | ||
| A Randomized, Double-Blind, Double Dummy, Parallel Group, Multicenter Variable Length Study to Assess the Efficacy and Safety of PT010 Relative to PT009 and Symbicort® in Adult and Adolescent Participants With Inadequately Controlled Asthma [NCT04609904] | Phase 3 | 2,200 participants (Anticipated) | Interventional | 2021-03-01 | Recruiting | ||
| An Open-label, Low Interventional Clinical Study Investigating Error Rates (Critical and Overall) Prior to Any Retraining in Correct Use of the ELLIPTA Dry Powder Inhaler (DPI) Compared to Other DPIs Including; DISKUS, Turbuhaler, HandiHaler and Breezhale [NCT03114969] | 450 participants (Actual) | Observational | 2017-06-08 | Completed | |||
| A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005, PT008, and Open-label Symbicort® Turbuhaler®, as an Active Control, on Lung Function Over a 24-Week Treatment Period in Subjects W [NCT02766608] | Phase 3 | 2,389 participants (Actual) | Interventional | 2016-05-31 | Completed | ||
| A Randomized, Open-Label, Two Period Crossover, Chronic Dosing, 1-Week, Pilot Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Inhalation Aerosol Administered With a Spacer Compared With Symbicort® Turbuhaler® in Subjects With [NCT04078126] | Phase 3 | 35 participants (Actual) | Interventional | 2019-09-10 | Completed | ||
| A Phase IV, 12-week, Randomised, Double-blind, Triple Dummy Study to Compare Single Inhaler Triple Therapy, Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) With Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) Based on Lung Functi [NCT03478696] | Phase 4 | 732 participants (Actual) | Interventional | 2018-06-25 | Completed | ||
| A Phase III, 12-week, Double-blind, Randomised, Parallel-group, Active-controlled, Multinational, Efficacy and Safety Study of Symbicort® Turbuhaler® 160/4.5 μg 2 Inhalations Twice Daily (Bid) Compared to Oxis® Turbuhaler® 4.5 μg 2 Inhalations Twice Daily [NCT01069289] | Phase 3 | 1,293 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| A Phase I, Randomized, Double-Blind, Single-Dose, Three-Period, Three-Treatment, Cross-Over Study Evaluating the Pharmacokinetics and Safety of a Single Dose of PT010, a Single Dose of PT009, and a Single Dose of Open-Label Symbicort® Turbohaler® in Healt [NCT02189304] | Phase 1 | 59 participants (Actual) | Interventional | 2014-06-01 | Completed | ||
| Study Comparing Bronchodilator Efficacy of Two Dry Powder Inhalers, Budesonide/Formoterol Easyhaler and Symbicort Turbuhaler; a Randomised, Double-blind, Double-dummy, Multicentre, Single Dose, Crossover Study in Asthmatic Subjects [NCT02308098] | Phase 3 | 72 participants (Actual) | Interventional | 2014-12-31 | Completed | ||
| A Retrospective Evaluation of the Effectiveness of Fixed-dose Combination Inhaled Corticosteroid /. Long-acting Beta Agonist (ICS/LABA) Therapy in the Management of Asthma in a Representative UK Primary Care Population [NCT01141465] | 815,377 participants (Actual) | Observational | 2001-01-31 | Completed | |||
| A Phase IV, 12-week, Randomised, Double-blind, Triple Dummy Study to Compare Single Inhaler Triple Therapy, Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) With Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) Based on Lung Functi [NCT03478683] | Phase 4 | 729 participants (Actual) | Interventional | 2018-06-25 | Completed | ||
| Physiological Responses to U-LABA/ICS With Emphasis on Exercise Performance in Well-Trained Individuals, Formoterol [NCT06105671] | 24 participants (Anticipated) | Interventional | 2023-12-15 | Not yet recruiting | |||
| A Multi-centre, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Anti-IgE Monoclonal Antibody to Treat Allergic Asthma Patients Not Adequately Controlled Despite Med/High ICS/LABA. [NCT03468790] | Phase 3 | 393 participants (Actual) | Interventional | 2018-05-09 | Completed | ||
| The Use of an Innovative Device for Therapeutic Adherence in Pediatric Asthma [NCT03788395] | Phase 4 | 18 participants (Actual) | Interventional | 2019-01-10 | Completed | ||
| A Double Blind, Double Dummy, Randomized, Two Way Cross-over Study to Compare the Effects of Z7200 and Symbicort® Turbohaler on Functional Respiratory Imaging Parameters in Asthmatic Patients. [NCT02227394] | Phase 2 | 20 participants (Actual) | Interventional | 2014-08-31 | Completed | ||
| Comparative Study Between Three Therapeutic Options for Treatment of Chronic Obstructive Pulmonary Disease Patients [NCT04520230] | Phase 4 | 45 participants (Actual) | Interventional | 2014-10-31 | Completed | ||
| Effectiveness of Single Inhaler Maintenance and Reliever Therapy With Spiromax® Budesonide/Formoterol (SMART) Versus Fixed Dose Treatment With Diskus® Fluticasone/Salmeterol in Patients With a Chronic Obstructive Pulmonary Disease (COPD) [NCT02477397] | Phase 3 | 201 participants (Actual) | Interventional | 2015-05-01 | Active, not recruiting | ||
| Phase Ⅱ Study of Bosentan in the Treatment of Stable Severe Chronic Obstructive Pulmonary Disease Patients [NCT02093195] | Phase 2 | 40 participants (Anticipated) | Interventional | 2013-12-31 | Recruiting | ||
| A Randomized, Double-Blind, Parallel Group, Multicenter 24 Week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler and Open-Label Symbicort® Turbuhaler® in Partici [NCT05202262] | Phase 3 | 630 participants (Anticipated) | Interventional | 2022-01-12 | Recruiting | ||
| A Double-blind, Randomised, Cross-over, Multi-centre Study, to Evaluate Onset of Effect in the Morning in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort®Turbuhaler® 320/9 μg, Compared With Seretide® Diskus® 50/500 [NCT00542880] | Phase 4 | 442 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy (SMART) in Asthma Patients Across Asia: SMARTASIA [NCT00939341] | Phase 4 | 862 participants (Actual) | Interventional | 2009-07-31 | Completed | ||
| An Open-Label, Randomized, Five-Period Cross-over, Single-dose Study to Compare Pharmacokinetics Profiles of Z7200 Medium Strength and Symbicort Turbohaler, With and Without Charcoal Blockade in Healthy Volunteers. [NCT02631941] | Phase 1 | 91 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| A Randomized, Multicenter, Placebo and Active-Controlled, Single-Dose, 4-Period, Crossover Study to Evaluate the Bronchodilating Effect of SYMBICORT pMDI Versus Advair Diskus and Ventolin HFA. [NCT00646620] | Phase 3 | 48 participants (Actual) | Interventional | 2003-04-30 | Completed | ||
| A 52 wk Randomized, Doubleblind, Single Dummy, Parallel Group Multicenter Phase 3 Study Comparing the Long Term Safety of Symbicort pMDI 4x160/4.5mcg Bid to SymbicortpMDI 2x160/4.5mcg Bid & Budesonide HFA pMDI 4x160mcg Bid in Adult and Adolescent Subjects [NCT00651768] | Phase 3 | 570 participants (Anticipated) | Interventional | 2003-08-31 | Completed | ||
| STUDY NUMBER: PMC-101-APT Usability and Adherence of Spiromax® Inhaler Device, Turbohaler® and Diskus® Inhaler Devices for Fixed Combination of Corticosteroid/Long-acting beta2- Agonist, in Adults With Asthma or COPD [NCT02757209] | 84 participants (Actual) | Interventional | 2016-04-30 | Completed | |||
| A 6-week, Phase III, Double-blind, Randomized, Multi-centre, Parallel-group Study Evaluating the Efficacy and Safety of 2 Actuations Symbicort®pMDI® 40/2.25 μg Twice Daily Compared With 1 Inhalation Symbicort Turbuhaler® 80/4.5 μg Twice Daily and 1 Inhala [NCT00536731] | Phase 3 | 742 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus as Needed Terbutaline in Mild-Moderate Persistent Asthma [NCT00849095] | Phase 3 | 860 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| The Comparisons of the Efficacy and Safety of Inhaled LAMA or LAMA+LABA or ICS+LABA for Patients in COPD C Group With Bronchiectasis [NCT02546297] | Phase 4 | 90 participants (Anticipated) | Interventional | 2017-09-15 | Enrolling by invitation | ||
| Onset of Action of Advair HFA 115/21 in Comparison to Symbicort pMDI 160/4.5 Measured by Impulse Oscillometry, IOS. [NCT00867737] | Phase 4 | 30 participants (Anticipated) | Interventional | 2008-09-30 | Recruiting | ||
| A 12-week, Randomised, Double Blind, Active-controlled, Multi-centre, Phase IIIB Study Comparing the Efficacy and Safety of SYMBICORT® pMDI 160/4.5 mg x 2 Actuations Twice Daily Versus Budesonide HFA pMDI 160 mg x 2 Actuations Twice Daily, in Adult/Adoles [NCT00419757] | Phase 3 | 558 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| A 12-week, Double-blind, Randomised, Parallel Group, Multi-centre, Study to Evaluate Efficacy and Safety of Budesonide/Formoterol (Symbicort Turbuhaler®) 320/9 µg One Inhalation Twice Daily on Top of Tiotropium (Spiriva®) 18 µg One Inhalation Once Daily [NCT00496470] | Phase 4 | 660 participants (Actual) | Interventional | 2007-05-31 | Completed | ||
| A Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 Micrograms, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults - a 26-week, Randomised, Open-label, Parallel-gr [NCT00385593] | Phase 3 | 654 participants (Actual) | Interventional | 2006-09-30 | Terminated | ||
| Bioequivalence Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 200/6 µg/Inhalation and Symbicort Turbohaler 200 µg/6 µg/Inhalation [NCT00964535] | Phase 1/Phase 2 | 87 participants (Actual) | Interventional | 2009-09-30 | Completed | ||
| A Six Month, Randomized, Open-Label, Safety Study of Symbicort (160/4.5mcg) Compared to Pulmicort Turbuhaler in Asthmatic Children Aged Six to Eleven Years - SAPLING [NCT00646529] | Phase 3 | 175 participants (Anticipated) | Interventional | 2002-07-31 | Completed | ||
| Symbicort Maintenance And Reliever Therapy - Experience in Real Life Setting in Malaysia - SMARTER Study [NCT00576316] | Phase 4 | 201 participants (Actual) | Interventional | 2008-01-31 | Completed | ||
| Yiqi Huoxue Huatan Granule for Reducing Mortality in COPD With Chronic Respiratory Failure: A Randomized, Double-blind, Placebo Controlled Trial [NCT04208581] | Phase 3 | 372 participants (Anticipated) | Interventional | 2019-10-08 | Enrolling by invitation | ||
| A 12 Week, Randomized, Double-Blind, Double-Dummy, Active-Controlled Study of SYMBICORT pMDI Administered Once Daily in Children and Adolescents 6 to 15 Years of Age With Asthma - SPROUT [NCT00646321] | Phase 3 | 540 participants (Anticipated) | Interventional | 2003-04-30 | Completed | ||
| Pharmacokinetic Pilot Study on Budesonide/Formoterol Device-metered Dry Powder Inhaler, Symbicort Turbuhaler; an Open, Single Center, Single Dose Study With 3-way Crossover Design in Healthy Subjects [NCT00868426] | Phase 1 | 12 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| A Comparison of Tolerability of 10 Inhalations of Symbicort® Turbuhaler® 160/4.5 μg and 10 Inhalations of Terbutaline Turbuhaler® 0.4 mg on Top of Symbicort® Turbuhaler® 160/4.5 μg 1 Inhalation Bid, Randomized, Double-blind, Cross Over, Phase III Study in [NCT00837967] | Phase 3 | 25 participants (Actual) | Interventional | 2009-01-31 | Completed | ||
| An Open-label Phase III, Multi-centre 52-week , Parallel-group Study Evaluating the Safety and Efficacy of Symbicort Turbuhaler 320/9 Twice Daily Compared With Standard Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) [NCT01070784] | Phase 3 | 328 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| Pharmacokinetic Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 320/9 Microg/Inhalation and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Single Centre, Single Dose [NCT01386996] | Phase 1 | 74 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| Randomised, Open-label, Parallel-group Study of Therapeutic Effect of Leukotriene Modulator Montelukast Alone or Combined With Inhaled Corticosteroid on Cough Variant Asthma [NCT01404013] | Phase 4 | 99 participants (Anticipated) | Interventional | 2012-02-29 | Recruiting | ||
| Effect of Charcoal on Gastrointestinal Absorption of Budesonide and Formoterol [NCT01423305] | Phase 1 | 20 participants (Actual) | Interventional | 2011-08-31 | Completed | ||
| A Comparison of Symbicort® SMART (160/4.5μg) and Symbicort® Turbuhaler 160/4.5 μg, Plus Terbutaline Turbuhaler 0.4 mg as Needed, for Treatment of Asthma - a 12-month, Randomized, Double-blind, Parallel Group, Active-controlled, Multinational Phase III Stu [NCT00839800] | Phase 3 | 2,091 participants (Actual) | Interventional | 2009-02-28 | Completed | ||
| Physician and Patient Perception of Adjustable Maintenance Dosing of Symbicort Turbuhaler [NCT00812682] | 217 participants (Actual) | Observational | 2006-09-30 | Completed | |||
| A Comparison of Symbicort® Single Inhaler Therapy (Symbicort Turbuhaler® 160/4.5mg, 1 Inhalation Two Times a Day (b.i.d.) Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults a -26-week, Randomized, Open-label, P [NCT00628758] | Phase 3 | 430 participants (Actual) | Interventional | 2005-12-31 | Completed | ||
| A Randomised, Open-Label, Single-Dose, Single-Centre, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of Symbicort pMDI 160/4.5µg Administered With a Spacer (With and Without Charcoal) and Symbicort pMDI 160/4.5µg Administered W [NCT02934607] | Phase 1 | 50 participants (Actual) | Interventional | 2016-11-04 | Completed | ||
| A 52-week, Randomised, Double-blind, Parallel-group, Multi-centre, Phase IIIB Study Comparing the Long Term Safety of SYMBICORT® pMDI 160/4.5 mg x 2 Actuations Twice Daily to Budesonide HFA pMDI 160 mg x 2 Actuations Twice Daily in Adult/Adolescent (≥12 Y [NCT00419952] | Phase 3 | 742 participants (Actual) | Interventional | 2007-02-28 | Completed | ||
| A Phase IIIB, 12-Month, Double-blind, Double-dummy,Randomised, Parallel-group, Multicentre Exacerbation Study of SYMBICORT® pMDI 160/4.5 μg x 2 Actuations Twice-daily and 80/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler® 4.5 μg x 2 I [NCT00419744] | Phase 3 | 1,200 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| Stepping Down of Asthma Medication in Controlled Asthma [NCT01961154] | 56 participants (Actual) | Interventional | 2012-10-31 | Completed | |||
| A Phase I, Randomized, Double-Blind Within Device, Single-Dose, Four-Period, Six-Treatment, Cross-Over Study Evaluating the Safety and Pharmacokinetics of Three Doses of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI), One [NCT01980615] | Phase 1 | 84 participants (Actual) | Interventional | 2013-11-30 | Completed | ||
| A Comparative Study of Efficacy and Safety of Genolar® and Xolar® in Treating Patients With Moderate to Severe Persistent Atopic Bronchial Asthma Inadequately Controlled With Stage 4 GINA (2017) Treatment [NCT04607629] | Phase 3 | 192 participants (Actual) | Interventional | 2018-06-20 | Completed | ||
| Non-interventional Surveillance of Effectiveness of Symbicort® Maintenance And Reliever Therapy (Symbicort® SMART) in the Treatment of Moderate and Severe Asthma [NCT00573222] | 330 participants (Actual) | Observational | 2007-11-30 | Completed | |||
| A Proof Of Concept Study To Evaluate Tiotropium as Add-on Therapy to Inhaled Budesonide/Formoterol Combination in COPD [NCT00996697] | Phase 4 | 23 participants (Actual) | Interventional | 2006-10-31 | Completed | ||
| A Rand, Doubleblind, Activecontrolled, Parallel-grp,Singledummy, Multicenter,12 wk Study to Assess the Effic.&Safety of Symbicort pMDI 2x160/4.5mcg QD Compared to Symb. pMDI 2x80/4.5mcg QD, Symb. pMDI 2x80/4.5mcg Bid and to Budesonide pMDI 2x160 Mcg QD in [NCT00646516] | Phase 3 | 615 participants (Anticipated) | Interventional | 2003-10-31 | Completed | ||
| A Two Stage Randomized, Open-Label, Parallel Group, Phase III, Multicenter, 7 Month Study to Assess the Efficacy & Safety of SYMBICORT pMDI Adminstered Either as Fixed or as an Adjustable Regimen Versus a Fixed Regimen of Advair in Subjects 12 Yrs of Age [NCT00646594] | Phase 3 | 1,200 participants (Anticipated) | Interventional | 2003-11-30 | Completed | ||
| Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study [NCT01432080] | Phase 2 | 12 participants (Actual) | Interventional | 2011-09-30 | Terminated(stopped due to Not meeting recruitment targets) | ||
| An Open-Label, Single-dose, Randomized, Five-Period Cross-over to Compare Pharmacokinetics Profiles of Z7200 and Symbicort Turbohaler, With and Without Charcoal Blockade in Healthy Volunteers. [NCT02237508] | Phase 1 | 90 participants (Actual) | Interventional | 2014-09-30 | Completed | ||
| Real Life Effectiveness in Asthma of Symbicort Single Inhaler Therapy [NCT00319306] | Phase 3 | 550 participants | Interventional | 2005-09-30 | Completed | ||
| A Phase 2, Randomized, Blinded, 5-period Cross-over, Placebo and Active Controlled, Multicenter, Dose-finding Study Comparing Single Doses of Formoterol 2.25 µg, 4.5 µg, and 9 µg Delivered Via Symbicort pMDI and Foradil® 12 µg Evaluating the Relative Bron [NCT01136655] | Phase 2 | 54 participants (Actual) | Interventional | 2010-09-30 | Completed | ||
| A 12-week, Double-blind, Randomized, Multi-centre, Parallel-group Study Evaluating the Efficacy Safety, and Patient Use (User Study) of Symbicort® (Budesonide/Formoterol) Breath Actuated Metered Dose Inhaler (BA MDI) 2x160/4.5 μg Twice Daily Compared With [NCT01360021] | Phase 3 | 214 participants (Actual) | Interventional | 2011-11-30 | Completed | ||
| A Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 µg, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults - a 26-Week, Randomised, Open-Label, Parallel-Group, Mul [NCT00252863] | Phase 3 | 1,600 participants | Interventional | 2004-12-31 | Completed | ||
| A 6-Month, Phase IIIA, Multi-Center,Randomised,Double-Blind, Double-Dummy, Parallel-Group Study of the Efficacy and Safety of Symbicort® Turbuhaler®+ Bricasol® pMDI Compared With Pulmicort® Turbuhaler®+Bricasol® pMDI in Chinese Patients With COPD [NCT00421122] | Phase 3 | 315 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| Pharmacokinetic Study Comparing Budesonide/Formoterol Easyhaler and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Double-dummy, Single Centre, Single Dose, Crossover Study in Healthy Subjects [NCT01627158] | Phase 1 | 72 participants (Actual) | Interventional | 2012-06-30 | Completed | ||
| Pharmacokinetic Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers, Two Batches of Symbicort Turbuhaler and Budesonide/Formoterol Easyhaler: Randomised, Double-blind, Double-dummy, Single Centre, Single Dose, Crossover Study in Healthy Subj [NCT01668121] | Phase 1 | 48 participants (Actual) | Interventional | 2012-08-31 | Completed | ||
| Comparison of the Efficacy and Safety of Budesonide/Formoterol Turbuhaler® Versus Terbutaline Nebulization as Reliever Therapy in Children With Asthma Presenting at the Emergency Room for Moderate Exacerbation [NCT04705727] | Phase 3 | 102 participants (Actual) | Interventional | 2021-08-23 | Terminated(stopped due to Not enough recruitment in th trial) | ||
| A Randomized, Blinded, Single-center Study in Mild to Moderate Asthmatics Over the Age of 12 Years Who Have a Viral-mediated Exacerbation and Are Treated With Symbicort or Pulmicort Flexhaler [NCT01218399] | 10 participants (Actual) | Interventional | 2009-09-30 | Completed | |||
| A 24-week Randomised Exploratory Open-Label Study Aiming To Characterise Changes In Airway Inflammation, Symptoms, Lung Function, And Reliever Use In Asthma Patients Using SABA (Salbutamol) Or Anti-Inflammatory Reliever (SYMBICORT®) As Rescue Medication I [NCT03924635] | Phase 4 | 40 participants (Actual) | Interventional | 2019-08-01 | Completed | ||
| Randomized, Single Blind, Parallel Group, Placebo Controlled, Multidose Study Comparing the Therapeutic Equivalence of a 3M Budesonide/Formoterol Fumarate Inhaler and a Symbicort® Reference Inhaler in Adult Subjects With Asthma [NCT03015259] | Phase 3 | 1,762 participants (Actual) | Interventional | 2016-12-29 | Completed | ||
| A Phase 3, 12-Week, Double-Blind, Randomized, Parallel-Group, Multicenter Study Investigating the Efficacy and Safety of Symbicort pMDI 80/2.25 μg, 2 Actuations Twice Daily, and Symbicort pMDI 80/4.5 μg, 2 Actuations Twice Daily, Compared With Budesonide [NCT02091986] | Phase 3 | 882 participants (Actual) | Interventional | 2014-04-30 | Completed | ||
| A 12-Week, Randomized, Open-Label, Parallel-Group Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® (160/4.5 and 320/9 mcg) as Compared With SYMBICORT® TURBOHALER® (200/6 and 400/12 mcg) as Treatment for Adult Pat [NCT02062463] | Phase 3 | 485 participants (Actual) | Interventional | 2014-05-28 | Completed | ||
| A 26 Week, Randomized, Double-blind, Parallel-group, Active Controlled, Multicenter, Multinational Safety Study Evaluating the Risk of Serious Asthma-related Events During Treatment With Symbicort®, a Fixed Combination of Inhaled Corticosteroid (ICS) (Bud [NCT01444430] | Phase 3 | 12,460 participants (Actual) | Interventional | 2011-12-31 | Completed | ||
| Pharmacokinetic Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 320/9 Microg/Inhalation and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Single Centre, Single Dose [NCT01593826] | Phase 1 | 72 participants (Actual) | Interventional | 2012-05-31 | Completed | ||
| Protective Role of Inhaled Steroids for Covid-19 Infection [NCT04331054] | Phase 3 | 146 participants (Actual) | Interventional | 2020-04-13 | Terminated(stopped due to Insufficient recruitment) | ||
| A Phase III, 24 Week, Randomized, Double Blind, Double Dummy, Parallel Group Study (With an Extension to 52 Weeks in a Subset of Subjects) Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI Administered Once Da [NCT02345161] | Phase 3 | 1,811 participants (Actual) | Interventional | 2015-01-23 | Completed | ||
| A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects With Moderate to Very Severe Chronic [NCT02497001] | Phase 3 | 1,902 participants (Actual) | Interventional | 2015-08-10 | Completed | ||
| A Randomized, Double-Blind, Double Dummy, Parallel Group, Multicenter Variable Length Study to Assess the Efficacy and Safety of PT010 Relative to PT009 and Symbicort® in Adult and Adolescent Participants With Inadequately Controlled Asthma [NCT04609878] | Phase 3 | 2,200 participants (Anticipated) | Interventional | 2020-12-15 | Recruiting | ||
| A 24-week, Double Blind, Double Dummy, Randomized, Multicentre, 2-arm Parallel Group, Active Controlled Clinical Trial of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Administered Via pMDI (CHF 1535) Versus the Fixed Combinatio [NCT03888131] | Phase 3 | 750 participants (Actual) | Interventional | 2018-07-30 | Completed | ||
| THE HCP ELIOT STUDY: Comparing Maintenance of Device Mastery With TURBOHALER© vs. SPIROMAX© in Healthcare Professionals naïve to Both Devices (The Easy Low Instruction Over Time [ELIOT] Study) [NCT02570425] | 516 participants (Actual) | Interventional | 2014-07-31 | Completed | |||
| SHAMAL: A Multicentre, Randomised, Open-Label, Parallel-Group, Active-Controlled, Phase IV Study to Assess the Reduction of Daily Maintenance ICS/LABA Treatment Towards Anti-Inflammatory Reliever Treatment in Patients With Severe Eosinophilic Asthma Treat [NCT04159519] | Phase 4 | 168 participants (Actual) | Interventional | 2020-07-27 | Completed | ||
| Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers [NCT01225913] | Phase 4 | 50 participants (Anticipated) | Interventional | 2007-10-31 | Recruiting | ||
| Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers [NCT00576069] | 60 participants (Anticipated) | Observational | 2007-10-25 | Recruiting | |||
| A 4-week, Open-label, Randomized, Multi-centre, Parallel-group Study Evaluating the Safety and Efficacy of 4 Actuations Symbicort® (Budesonide/Formoterol) HFA pMDI 40/2.25 μg Twice Daily, With and Without Spacer, in Children (6-11 Years) With Asthma [NCT00536913] | Phase 3 | 107 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| Multicenter Randomized Parallel-Group 6-Week Treatment Clinical Study to Assess BE of Budesonide 80 μg and Formoterol Fumarate Dihydrate 4.5 μg Inhalation Product in Comparison With Reference Product, Symbicort® in Adult Asthma Patients [NCT05322707] | Phase 3 | 1,485 participants (Actual) | Interventional | 2022-04-15 | Completed | ||
| A Comparison of the Bronchodilating Activity of Symbicort Pressure Metered Dose Inhaler (pMDI) 160/4.5 Used in the Conventional Manner and With a Valved Spacer Holding Chamber (Aerochamber Plus) [NCT00915538] | Phase 4 | 16 participants (Actual) | Interventional | 2009-07-31 | Completed | ||
| A 12-Week Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX(R) 160/4.5 mcg Inhalation Powder Versus SYMBICORT(R) TURBOHALER(R) 200/6 mcg in Adult and Adolescent Patients With Persistent Asthma [NCT01803555] | Phase 3 | 605 participants (Actual) | Interventional | 2013-07-04 | Completed | ||
| Pharmacokinetic Pilot Study Comparing Three Formulations of Budesonide/Formoterol Easyhaler 160/4.5 Microg/Inhalation and Symbicort Turbuhaler: A Randomised, Open, Single Centre, Single Dose, Crossover Study in Healthy Subjects [NCT03073057] | Phase 1 | 20 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| Efficacy and Tolerability Study of Symbicort Turbuhaler(160/4.5µg/Inhalation,2inhalations Twice Daily) Added to Atrovent (20µg/Inhalation, 2 Inhalations 4 Times Daily)+Theophylline SR(0.1g/Tablet,1 Tablet p.o. Twice Daily) Compared With Atrovent+Theophyll [NCT01415518] | Phase 4 | 581 participants (Actual) | Interventional | 2011-09-01 | Completed | ||
| GR Activity in Induced Sputum Macrophages, and a Change in Inflammatory Biomarkers 2-hours After a Single Dose of Either Symbicort®/Budesonide/Formoterol or in Chronic Obstructive Pulmonary Disease (COPD) [NCT01787097] | Phase 4 | 31 participants (Actual) | Interventional | 2013-01-31 | Completed | ||
| A Randomised, Parallel-group, Open-label, Multicentre, 3-month Phase IV, Efficacy and Tolerability Study of Budesonide/Formoterol (Symbicort® Turbuhaler® 160/4.5μg/Inhalation, 2 Inhalations Twice Daily) Added to Tiotropium (SpirivaTM 18 μg/Inhalation, 1 I [NCT01397890] | Phase 4 | 793 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| A Randomized, Blinded, Parallel Group, Placebo-Controlled, Multiple Dose, Multicenter, Multinational Study to Compare the Therapeutic Equivalence of a Budesonide 80 μg/Formoterol Fumarate Dihydrate 4.5 μg Inhalation Aerosol (Manufactured by Catalent for W [NCT02495168] | Phase 3 | 1,714 participants (Actual) | Interventional | 2017-01-13 | Completed | ||
| A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® Pressurized Metered-Dose Inhaler (pMDI) 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalati [NCT02157935] | Phase 3 | 2,026 participants (Actual) | Interventional | 2014-06-27 | Completed | ||
| A 12-wk, Rand., Double-blind, Double Dummy, Multi-ctr., Phase IV Study Comparing Efficacy and Safety of SYMBICORT® pMDI 160/4.5 ug x 2 Actuations Twice Daily Versus Pulmicort® (Budesonide Inhalation Powder DPI) 180 ug x 2 Inhalations Twice Daily, in Adult [NCT00702325] | Phase 4 | 311 participants (Actual) | Interventional | 2008-06-30 | Completed | ||
| Multicenter, Randomized, Double-blind, Double-dummy, National, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Flamboyant 200/12 Association in the Treatment of Adults With Severe Asthma . [NCT04191447] | Phase 3 | 134 participants (Anticipated) | Interventional | 2022-07-22 | Recruiting | ||
| A Randomised, Multi-centre, Open Label, Cross-over Non-inferiority Study to Evaluate Efficacy, Safety and Tolerability of Neumoterol 400 and Symbicort Forte in Adults With Asthma [NCT02233803] | Phase 4 | 239 participants (Actual) | Interventional | 2014-11-14 | Completed | ||
| Investigating the Effects of Symbicort on the Ventilatory Kinematics in Patients With Obstructive Disease With Optoelectronic Plethysmography [NCT01712854] | Phase 4 | 9 participants (Actual) | Interventional | 2012-03-31 | Terminated(stopped due to Closed by study sponsor; PI left the institution; responsible party changed to Columbia) | ||
| Multicenter, Randomized, Double-blind, Double-dummy, National, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Flamboyant 125/12 Association in the Treatment of Adults With Moderate Asthma . [NCT04191434] | Phase 3 | 134 participants (Anticipated) | Interventional | 2022-07-22 | Recruiting | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
Mean use of as needed medication during the treatment period (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Inhalations (Mean) |
|---|---|
| SMART | 1.03 |
| Conv. Best Practice | 1.02 |
Peak expiratory flow (PEF) (NCT00385593)
Timeframe: 6 months (end of the study)
| Intervention | L/min (Mean) |
|---|---|
| SMART | 405.9 |
| Conv. Best Practice | 400.6 |
Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral Glucocorticosteroids (GCS) treatment for at least 3 days. (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Days (Mean) |
|---|---|
| SMART | 174.39 |
| Conv. Best Practice | 178.97 |
Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral (GCS) treatment for at least 3 days. (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Exacerbations (Number) |
|---|---|
| SMART | 24 |
| Conv. Best Practice | 34 |
Mean micrograms/day of inhaled steroids (beclomethasone dipropionate equivalents) (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | micrograms (Mean) |
|---|---|
| SMART | 799 |
| Conv. Best Practice | 1184 |
The ACQ is a 7-point scale with scores ranging from 0 (very well controlled) to 6 (very badly controlled) (NCT00385593)
Timeframe: Daily 14 days prior to each of visit 2-4
| Intervention | Scores on a scale (Mean) |
|---|---|
| SMART | 0.99 |
| Conv. Best Practice | 1.08 |
Rate of exacerbations per subject-year (NCT00419744)
Timeframe: 12 months
| Intervention | Rate (Number) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.639 |
| SYM 80/4.5 X 2 BID | 0.745 |
| FOR 4.5 X 2 BID | 1.029 |
Change from baseline of Dyspnea symptoms evaluated using the breathlessness diary, a 5-point Likert-type scale, ranging from 0 to 4 with higher scores indicating a more severe manifestation of the Dyspnea symptom. Change from baseline was calculated by averaging treatment period Dyspnea scores and subtracting the baseline Dyspnea scores. (NCT00419744)
Timeframe: 12 months
| Intervention | Scores on a scale (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -0.30 |
| SYM 80/4.5 X 2 BID | -0.29 |
| FOR 4.5 X 2 BID | -0.24 |
Change in evening PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline evening PEF value. (NCT00419744)
Timeframe: 12 months
| Intervention | L/min (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 17.62 |
| SYM 80/4.5 X 2 BID | 17.77 |
| FOR 4.5 X 2 BID | 14.08 |
Change in morning PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline morning PEF value. (NCT00419744)
Timeframe: 12 months
| Intervention | L/min (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 19.82 |
| SYM 80/4.5 X 2 BID | 19.61 |
| FOR 4.5 X 2 BID | 15.81 |
Change in pre-dose FEV1 from baseline to the average of the randomized treatment period, as calculated by averaging treatment period FEV1 values and subtracting the pre-dose value. (NCT00419744)
Timeframe: 12 months
| Intervention | Liters (L) (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.07 |
| SYM 80/4.5 X 2 BID | 0.07 |
| FOR 4.5 X 2 BID | 0.04 |
Change from baseline in the SGRQ overall score, as calculated by averaging treatment period SGRQ scores and subtracting the baseline SGRQ scores. The SGRQ contains 3 domains: Symptoms (distress due to respiratory symptoms, 8 questions), Activity (disturbance of physical activity, 16 questions), and Impacts (overall impact on daily life and well-being, 26 questions). Lower scores are associated with less severe symptoms. (NCT00419744)
Timeframe: 12 months
| Intervention | Scores on a scale (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -6.23 |
| SYM 80/4.5 X 2 BID | -5.00 |
| FOR 4.5 X 2 BID | -5.71 |
Number of COPD-related exacerbations per patient-treatment year. COPD-related exacerbation was defined as worsening COPD that required a course of oral steriods for treatment and/or hospitalization. (NCT00419744)
Timeframe: 12 months
| Intervention | Exacerbations (Number) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.75 |
| SYM 80/4.5 X 2 BID | 0.84 |
| FOR 4.5 X 2 BID | 1.14 |
Change from baseline in the use of beta-2 agonists, as calculated by averaging treatment period inhalations per day and subtracting the baseline number of inhalations per day. (NCT00419744)
Timeframe: 12 months
| Intervention | Number of inhalations (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -1.21 |
| SYM 80/4.5 X 2 BID | -1.03 |
| FOR 4.5 X 2 BID | -0.28 |
"Change from baseline in average of daily scores for daytime asthma over 12 weeks of treatment, with baseline value as covariate.~Daily scale:~0 = No symptoms~1 = Mild symptoms~2 = Moderate symptoms~3 = Severe symptoms" (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | -0.40 |
| Budesonide | -0.30 |
"The assessment was made using a 5-point Likert scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1 and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses." (NCT00419757)
Timeframe: Baseline and week 12
| Intervention | Percent of Participants (Number) |
|---|---|
| Symbicort | 88.70 |
| Budesonide | 86.30 |
"Change from baseline in average of daily scores for nighttime asthma over 12 weeks of treatment, with baseline value as covariate.~Daily scale:~0 = No symptoms~1 = Mild symptoms~2 = Moderate symptoms~3 = Severe symptoms" (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | -0.40 |
| Budesonide | -0.30 |
Change from baseline in percentage of rescue-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 19.70 |
| Budesonide | 17.70 |
Changes in pre-dose FEV1 from baseline to the average value over the treatment period, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline, 2, 6 and 12 weeks
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort | 0.16 |
| Budesonide | 0.11 |
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Liters/minutes (Least Squares Mean) |
|---|---|
| Symbicort | 25.40 |
| Budesonide | 19.90 |
Mean scores (5-points scale, where 1-means the most positive opinion and 5-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 88.45 |
| Budesonide | 80.60 |
Mean scores (6-points scale, where 1-means the most positive opinion and 6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 87.20 |
| Budesonide | 82.50 |
Asthma Events, defined as any of: decrease in lung function (FEV1 or AM PEF), use of rescue medication over maximum allowed per day, night awakening requiring use of rescue medication, exacerbation of asthma requiring medical assistance, use of not allowed asthma medication (NCT00419757)
Timeframe: 12 weeks
| Intervention | Percentage of Participants (Number) |
|---|---|
| Symbicort | 25.20 |
| Budesonide | 31.70 |
"The assessment was made using a 5-point scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses." (NCT00419757)
Timeframe: Baseline and week 12
| Intervention | Perscentage of Participants (Number) |
|---|---|
| Symbicort | 92.00 |
| Budesonide | 84.60 |
Change from baseline in percentage of symptom-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 24.40 |
| Budesonide | 21.00 |
Mean scores (6 or 5-points scale, where 1-means the most positive opinion and 5/6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 90.67 |
| Budesonide | 86.66 |
"Percentage of participants with Withdrawals Due to Pre-defined Asthma Events as recorded in CRF. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated." (NCT00419757)
Timeframe: 12 weeks
| Intervention | Percentage of Participants (Number) |
|---|---|
| Symbicort | 2.10 |
| Budesonide | 6.50 |
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks with baseline as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Liters/minutes (Least Squares Mean) |
|---|---|
| Symbicort | 20.60 |
| Budesonide | 15.80 |
Change from baseline in rescue medication use over 12 weeks of treatment with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | puffs/day (Least Squares Mean) |
|---|---|
| Symbicort | -0.80 |
| Budesonide | -0.60 |
Change from baseline in percentage of nights with awakenings due to asthma over 12 weeks of treatment, with baseline value as covariate. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of nights (Least Squares Mean) |
|---|---|
| Symbicort | 5.40 |
| Budesonide | 5.50 |
"Number of participants with positive response to Item 5 in questionnaire During the past week, you were satisfied with how quickly you felt your study medication begin to work. The scale was scored on a 5-point Likert scale from strongly agree to strongly disagree. A positive response was defined as a response of strongly agree or somewhat agree" (NCT00419952)
Timeframe: 1 week
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 165 |
| Budesonide | 157 |
Change in pre-dose FEV1 from baseline (end of run-in, visit 3) to the average of the randomized treatment period (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Symbicort | 0.08 |
| Budesonide | -0.01 |
"Calculated as the number of rescue-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % rescue-free days in the baseline period and the active treatment period. A rescue-free day was one in which the patient answered no to having used rescue medication that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Percentage of Rescue Free Day (Least Squares Mean) |
|---|---|
| Symbicort | 15.88 |
| Budesonide | 10.62 |
"Calculated as the number of asthma control days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % asthma control days in the baseline period and the active treatment period. An asthma control day was one in which the patient answered no to having symptoms and 0 to the use of rescue medication that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | percentage of Asthma-control day (Least Squares Mean) |
|---|---|
| Symbicort | 16.68 |
| Budesonide | 11.62 |
Overall score - change from baseline to end of treatment. For 11 individual attributes, expectations were subtracted from the outcomes. This difference and the importance rating were combined in a weighted average which was then multiplied by the raw satisfaction measure. The final derived satisfaction measure was transformed to a 0 to 100 scale, with higher scores representing greater satisfaction. (NCT00419952)
Timeframe: Baseline and 52 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 47.99 |
| Budesonide | 45.64 |
Number of participants with at least 1 exacerbation (NCT00419952)
Timeframe: 52 Weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 29 |
| Budesonide | 51 |
Total ventricular runs - number of participants with shift normal (<1) to high (≥1) from baseline to week 2. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 2 |
| Budesonide | 1 |
An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization. (NCT00419952)
Timeframe: 52 Weeks
| Intervention | Exacerbations (Number) |
|---|---|
| Symbicort | 36 |
| Budesonide | 61 |
QT interval corrected using the Fridericia formula [QTc (Frid)] - Change from baseline to end of treatment (NCT00419952)
Timeframe: Baseline and 52 weeks
| Intervention | msec (Least Squares Mean) |
|---|---|
| Symbicort | -0.11 |
| Budesonide | -0.31 |
Change in AM PEF from baseline (mean over the 2 weeks run-in) to the average of the randomized treatment period. (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Liters/minute (Least Squares Mean) |
|---|---|
| Symbicort | 30.13 |
| Budesonide | 19.73 |
"Calculated as the number of symptom-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % symptom-free days in the baseline period and the active treatment period. A symptom-free day was one in which the patient answered no to having symptoms that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | percentage of Symptom-free day (Least Squares Mean) |
|---|---|
| Symbicort | 9.46 |
| Budesonide | 7.58 |
Total ectopic ventricular (VE) beats - number of participants with shift from normal (<50) to high (≥50) from baseline to visit 4. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 4 |
| Budesonide | 3 |
Total ectopic supraventricular (VE) beats - number of participants with shift normal (<50) to high (≥50) from baseline to visit 4. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 4 |
| Budesonide | 3 |
"Number of participants with positive response to Item 2 in questionnaire During the past week,you could feel your study medication begin to work right away. A positive response was defined as a response of strongly agree or somewhat agree" (NCT00419952)
Timeframe: 1 week
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 172 |
| Budesonide | 158 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.325 |
| Placebo+Tiotropium | -0.202 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.143 |
| Placebo+Tiotropium | -0.006 |
Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.266 |
| Placebo+Tiotropium | 0.106 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 not performed to 1performed) and rank the difficulty of performing each of those activities (score ranging from 0 so difficult that the activity could not be carried out by the patient on their own to 5 activity was not at all difficult to carry out. Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.202 |
| Placebo+Tiotropium | 0.07 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.177 |
| Placebo+Tiotropium | -0.049 |
Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.26 |
| Placebo+Tiotropium | 0.149 |
Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12 (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.353 |
| Placebo+Tiotropium | 0.19 |
Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.07 |
| Placebo+Tiotropium | 0.014 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 2.82 |
| Placebo+Tiotropium | -5.54 |
Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.165 |
| Placebo+Tiotropium | 0.042 |
Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.214 |
| Placebo+Tiotropium | 0.083 |
Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.064 |
| Placebo+Tiotropium | -0.001 |
Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.078 |
| Placebo+Tiotropium | 0.014 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.184 |
| Placebo+Tiotropium | -0.061 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.246 |
| Placebo+Tiotropium | -0.079 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.197 |
| Placebo+Tiotropium | -0.045 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.012 |
| Placebo+Tiotropium | -0.065 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.404 |
| Placebo+Tiotropium | -0.28 |
Daily diary record - Total, 24 hours, during the night, and during the day. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -1.024 |
| Placebo+Tiotropium | -0.347 |
Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.279 |
| Placebo+Tiotropium | 0.022 |
Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.417 |
| Placebo+Tiotropium | -0.124 |
Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.745 |
| Placebo+Tiotropium | -0.371 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.054 |
| Placebo+Tiotropium | -0.046 |
"Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit).~SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life." (NCT00496470)
Timeframe: Baseline and 12 weeks
| Intervention | Score on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -4.12 |
| Placebo+Tiotropium | -1.99 |
Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation (NCT00496470)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort+Tiotropium | 25 |
| Placebo+Tiotropium | 61 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.96 |
| Placebo+Tiotropium | 0.99 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.97 |
| Placebo+Tiotropium | 0.98 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.95 |
| Placebo+Tiotropium | 0.95 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.91 |
| Placebo+Tiotropium | 0.97 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 5.12 |
| Placebo+Tiotropium | -3.52 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 16.71 |
| Placebo+Tiotropium | 1.1 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 20.4 |
| Placebo+Tiotropium | 5.2 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.169 |
| Placebo+Tiotropium | -0.018 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.209 |
| Placebo+Tiotropium | 0.014 |
Change in the Morning PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| Symbicort pMDI | 12.88 |
| Symbicort Turbuhaler | 13.78 |
| Pulmicort Turbuhaler | 4.59 |
"Change in the Percentage of Nights With Awakenings Due to Asthma from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. The participants answered Yes or No whether she/he woke up during the night due to asthma." (NCT00536731)
Timeframe: Baseline and 6 weeks
| Intervention | Percentage of night (Mean) |
|---|---|
| Symbicort pMDI | -14.0 |
| Symbicort Turbuhaler | -14.0 |
| Pulmicort Turbuhaler | -8.3 |
Change in the Percentage of Rescue Free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Rescue-free Day defined as day and night with no use of rescue medication. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort pMDI | 24.0 |
| Symbicort Turbuhaler | 26.2 |
| Pulmicort Turbuhaler | 17.2 |
Change in the Percentage of Symptom-free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Symptom-free Day: no symptoms (asthma symptom score=0) night and day, and no awakenings due to asthma. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort pMDI | 12.5 |
| Symbicort Turbuhaler | 15.3 |
| Pulmicort Turbuhaler | 9.1 |
Change in the Use of Rescue Medication (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort pMDI | -0.21 |
| Symbicort Turbuhaler | -0.20 |
| Pulmicort Turbuhaler | -0.13 |
Change in the Use of Rescue Medication (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort pMDI | -0.41 |
| Symbicort Turbuhaler | -0.39 |
| Pulmicort Turbuhaler | -0.19 |
Change in the Use of Rescue Medication (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort pMDI | -0.62 |
| Symbicort Turbuhaler | -0.58 |
| Pulmicort Turbuhaler | -0.32 |
Change in the Percentage of Symptom Control Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Asthma Control Day: no symptoms (asthma symptom score=0) night and day, no awakenings due to asthma, no rescue medication. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort pMDI | 12.7 |
| Symbicort Turbuhaler | 15.1 |
| Pulmicort Turbuhaler | 9.1 |
Change in the Asthma Symptom Score (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort pMDI | -0.21 |
| Symbicort Turbuhaler | -0.24 |
| Pulmicort Turbuhaler | -0.15 |
Change in the Asthma Symptom Score (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort pMDI | -0.24 |
| Symbicort Turbuhaler | -0.27 |
| Pulmicort Turbuhaler | -0.15 |
Change in the Asthma Symptom Score (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort pMDI | -0.45 |
| Symbicort Turbuhaler | -0.51 |
| Pulmicort Turbuhaler | -0.30 |
Change in the Evening PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| Symbicort pMDI | 12.34 |
| Symbicort Turbuhaler | 10.80 |
| Pulmicort Turbuhaler | 1.43 |
Change in the FEV1from baseline to week 6 (calculated as a mean using all available data after randomization) (NCT00536731)
Timeframe: Baseline to 6 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort pMDI | 0.095 |
| Symbicort Turbuhaler | 0.147 |
| Pulmicort Turbuhaler | 0.112 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| With Spacer | -0.21 |
| Without Spacer | -0.14 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| With Spacer | -0.30 |
| Without Spacer | -0.19 |
Ratio between the value at the end of treatment and the value at start of treatment, including only patients with values at both baseline and end of treatment (NCT00536913)
Timeframe: At baseline and 4 weeks
| Intervention | Ratio (Geometric Mean) |
|---|---|
| With Spacer | 0.86 |
| Without Spacer | 1.03 |
Change in average value from the run-in to the treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation. Missing data between the first and last entry were estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| With Spacer | 27.00 |
| Without Spacer | 15.30 |
Changes in FEV1 from baseline to the mean value at 2 weeks to 4 weeks with the baseline value as a covariate. (NCT00536913)
Timeframe: At baseline, at 2 weeks and 4 weeks
| Intervention | Liters (Mean) |
|---|---|
| With Spacer | 0.17 |
| Without Spacer | 0.14 |
Change in average value from the run-in to the treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry were estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| With Spacer | 28.70 |
| Without Spacer | 19.50 |
Change in Percentage of nights with awakenings, average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Percentage of nights (Mean) |
|---|---|
| With Spacer | -13.80 |
| Without Spacer | -8.20 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| With Spacer | -0.25 |
| Without Spacer | -0.28 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| With Spacer | -0.20 |
| Without Spacer | -0.21 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0930 |
| Seretide Diskus | 0.0280 |
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (run-in, and washout) and day 1 of treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1120 |
| Seretide Diskus | 0.0440 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 15.8 |
| Seretide Diskus | 9.6 |
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (run-in, and washout) and day 1 of treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0950 |
| Seretide Diskus | 0.0490 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 11.6 |
| Seretide Diskus | 6.1 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0160 |
| Seretide Diskus | 0.0030 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.21 |
| Seretide Diskus | 0.14 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1220 |
| Seretide Diskus | 0.1030 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1470 |
| Seretide Diskus | 0.1060 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0310 |
| Seretide Diskus | 0.0590 |
The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 15.1 |
| Seretide Diskus | 13.4 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 19.9 |
| Seretide Diskus | 16.7 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 4 |
| Seretide Diskus | 1.8 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minutes (Mean) |
|---|---|
| Symbicort Turbuhaler | 4.8 |
| Seretide Diskus | 7.9 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1920 |
| Seretide Diskus First | 0.1240 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 6 with 0=worst and 6 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.24 |
| Seretide Diskus | 0.19 |
Difference/change in ACQ-5 scores between baseline and mean of 3 months and 6 months after SMART treatment. ACQ-5 is a 5 question patient reported outcome measuring level of asthma control during the past 7 days and it is scored on scale of 0-6. 0 indicates no symptoms and 6 represents severe symptoms (NCT00576316)
Timeframe: 6 months after each patient was initially treated with Symbicort SMART
| Intervention | scores on a scale (Mean) |
|---|---|
| Symbicort 160/4.5 Turbuhaler | -0.97 |
Difference/change in SATQ score between baseline and mean of 3 months and 6 months after SMART treatment as analysed by paired t-test. SATQ is a patient reported questionnaire which consists of 26 questions and scored to a scale of 1-7, the higher score indicating a greater level of satisfaction (NCT00576316)
Timeframe: 6 months after each patient was initially treated with Symbicort SMART
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort 160/4.5 Turbuhaler | 0.37 |
Quality-of-Life assessment; grouped in four domains;activity limitation, symptoms, emotional function and exposure to environmental stimuli, using with a scale from 1 to 7 where 1 represents the greatest possible impairment and 7 represents the least impairment. (NCT00628758)
Timeframe: Baseline and 26 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort | 3.98 |
| Conventional BP | 3.97 |
Time to severe exacerbation among patients (NCT00628758)
Timeframe: 26 weeks
| Intervention | days (Mean) |
|---|---|
| Symbicort | 120.3 |
| Conventional Best Practice (BP) | 103.7 |
Mean use of as-needed medication per day during treatment period (NCT00628758)
Timeframe: Daily recording during the treatment period of 26 weeks
| Intervention | inhalations per day (Mean) |
|---|---|
| Symbicort | 0.91 |
| Conventional BP | 0.68 |
Total number of severe asthma exacerbations per treatment group (NCT00628758)
Timeframe: 26 weeks
| Intervention | Severe Exacerbations (Number) |
|---|---|
| Symbicort | 10 |
| Conventional BP | 10 |
Diary assessment of total (percent) days free from rescue medication use for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 29.31 |
| Budesonide | 17.70 |
Diary assessment of total daily puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -1.27 |
| Budesonide | -0.62 |
Total number of participants with any first predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma medication) (NCT00702325)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 57 |
| Budesonide | 67 |
Total number of participants who withdrew due to a predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma meds) (NCT00702325)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 18 |
| Budesonide | 28 |
There are 5 questions in the survey, and each question has 5 responses (total score for each question can range from 1 to 5). To score the survey, responses to the 5 questions are added to yield a total score that ranges from 5 (poor control of asthma control) to 25 (complete control of asthma). Score of 20 or higher was indicative of well-controlled asthma. (NCT00702325)
Timeframe: 12 weeks
| Intervention | Proportion of Participants (Number) |
|---|---|
| Symbicort | 0.524 |
| Budesonide | 0.518 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at first week of treatment - During the past week, you could feel your medication begin to work right away (NCT00702325)
Timeframe: 1 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 95 | 81 |
| Symbicort | 113 | 101 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at first week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work. (NCT00702325)
Timeframe: 1 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 83 | 70 |
| Symbicort | 96 | 86 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at last week of treatment - During the past week, you could feel your medication begin to work right away (NCT00702325)
Timeframe: 12 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 112 | 95 |
| Symbicort | 123 | 109 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at last week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work. (NCT00702325)
Timeframe: 12 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 99 | 81 |
| Symbicort | 112 | 100 |
Diary assessment of number (percent) of days free from asthma symptoms by ICS dose at entry; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 23.99 |
| Budesonide | 17.55 |
Diary assessment of number of nights free from awakenings due to asthma; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Number of nights (Mean) |
|---|---|
| Symbicort | 17.51 |
| Budesonide | 11.85 |
Diary assessment of daytime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS) (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.33 |
| Budesonide | -0.24 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort | 21.61 |
| Budesonide | 7.67 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort | 25.34 |
| Budesonide | 7.53 |
Diary assessment of nighttime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS) (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.38 |
| Budesonide | -0.26 |
Mean change of the FEF (25-75%) value at the baseline (Visit 3) compared to average value of the FEF (25-75%) recorded at visits during treatment period (to week 12). The mean change was calculated. (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/second (Mean) |
|---|---|
| Symbicort | 0.21 |
| Budesonide | 0.12 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.16 |
| Budesonide | 0.07 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.14 |
| Budesonide | 0.07 |
Diary assessment of total asthma symptoms score (treatment average) by Inhaled Corticosteroid (ICS) dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.35 |
| Budesonide | -0.23 |
Mean change in overall score at end of treatment for participants age 17 years and older (scores ranged from 1 to 7, with higher scores indicating better quality of life); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 0.55 |
| Budesonide | 0.33 |
There are 6 questions in the survey, and each question has 5 responses (total score for each question can range from 6 to 13). Responses to the 6 questions were added to yield a total score that ranged from 36 to 78. Scoring is based on a norm-based method. Higher AIS scores indicated more asthma impact and poorer quality of life; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period. (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -4.05 |
| Budesonide | -2.72 |
Diary assessment of number (percent) of asthma-control days (defined as days that were free of symptoms and nighttime and daytime rescue medication use); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 21.89 |
| Budesonide | 15.12 |
Diary assessment of total daytime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -0.48 |
| Budesonide | -0.27 |
Diary assessment of total nighttime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -0.79 |
| Budesonide | -0.35 |
The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period. (NCT00837967)
Timeframe: up to 740 min after start dosing for each treatment day
| Intervention | mEq/L (Mean) |
|---|---|
| Symbicort | 4.01 |
| Terbutaline | 3.88 |
The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period. (NCT00837967)
Timeframe: up to 740 min after start dosing for each treatment day
| Intervention | beats/min (Mean) |
|---|---|
| Symbicort | 70.0 |
| Terbutaline | 74.1 |
The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period. (NCT00837967)
Timeframe: up to 740 min after start dosing for each treatment day
| Intervention | mmHg (Mean) |
|---|---|
| Symbicort | 115.3 |
| Terbutaline | 114.9 |
The mean AUC of QTcF (ECG interval measured from the beginning of the Q wave to the end of the T wave, corrected for heart rate using Fridericia's formula)was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period. (NCT00837967)
Timeframe: up to 740 min after start dosing for each treatment day
| Intervention | ms (Mean) |
|---|---|
| Symbicort | 411.71 |
| Terbutaline | 414.33 |
The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period. (NCT00837967)
Timeframe: up to 140 min after start dosing for each treatment day
| Intervention | mg/dLiters (Mean) |
|---|---|
| Symbicort | 121.1 |
| Terbutaline | 129.5 |
Total number of adverse events (NCT00837967)
Timeframe: 3 days
| Intervention | adverse events (Number) |
|---|---|
| Symbicort | 14 |
| Terbutaline | 24 |
The mean value from the treatment period was presented here. (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | Nights With Awakening(s) (Mean) |
|---|---|
| Symbicort SMART | 15.7 |
| Symbicort+Terbutaline As Needed | 17.5 |
The mean value of total daily number of inhalations from the treatment period for use of as-needed medication (daytime, night-time). (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | inhalations/day (Mean) |
|---|---|
| Symbicort SMART | 1.21 |
| Symbicort+Terbutaline As Needed | 1.46 |
Mild asthma exacerbation was defined as morning PEF ≥20% below baseline, daily as-needed medication use ≥2 inhalations above baseline, or a night with awakening due to asthma symptoms. The percentage of participants who had experienced mild asthma exacerbation(s) at the end of the study was presented here. (NCT00839800)
Timeframe: up to 52 weeks
| Intervention | percentage of participants (Number) |
|---|---|
| Symbicort SMART | 71 |
| Symbicort+Terbutaline As Needed | 80 |
The mean value for Weeks 4, 12, 24, 36 and 52 was analysed. (NCT00839800)
Timeframe: 4, 12, 24, 36 and 52 weeks after randomization
| Intervention | Liter (L) (Geometric Mean) |
|---|---|
| Symbicort SMART | 2.258 |
| Symbicort+Terbutaline As Needed | 2.222 |
Asthma exacerbation was defined as deterioration in asthma leading to oral glucocorticosteroid [GCS] treatment, hospitalization, or emergency room [ER] treatment. (NCT00839800)
Timeframe: week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Symbicort SMART | 16 |
| Symbicort+Terbutaline As Needed | 22 |
A symptom-free day was defined as a day without daytime or night-time symptoms and without night-time awakenings due to asthma symptoms. The mean value was presented here. (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | symptom-free days (Mean) |
|---|---|
| Symbicort SMART | 45.5 |
| Symbicort+Terbutaline As Needed | 41.6 |
An asthma-control day was defined as a a night and day with no asthma symptoms, no awakenings due to asthma symptoms, and no as-needed medication use. The mean value from the treatment period was presented here. (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | percentage of asthma-control days (Mean) |
|---|---|
| Symbicort SMART | 41.7 |
| Symbicort+Terbutaline As Needed | 37.9 |
The ACQ developed by Juniper and colleagues (Juniper et al 1999) was used without the FEV1 and Beta 2-agonist questions. The Asthma Control Questionnaire has 5 questions that are assessed on a 7-point scale from 0 to 6 where 0 represents good control and 6 represents poor control. The overall score is the mean of the five responses. At least 4 out of the 5 questions must have been answered to provide a value. The mean of the overall score for Weeks 4 to 52 was presented here. (NCT00839800)
Timeframe: 4, 12, 24, 36 and 52 weeks after randomization
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort SMART | 1.162 |
| Symbicort+Terbutaline As Needed | 1.289 |
The mean value from the treatment period for Total Asthma Symptom Score (total score: 0 is best - no asthma symptoms; 6 is worst). (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort SMART | 1.12 |
| Symbicort+Terbutaline As Needed | 1.22 |
The mean value from a 52-week treatment period. (NCT00839800)
Timeframe: 2-week run-in period (14 - 18 days before randomization - week 0) and a 52-week treatment period
| Intervention | L/min (Mean) |
|---|---|
| Symbicort SMART | 334.2 |
| Symbicort+Terbutaline As Needed | 327.8 |
The mean value from a 52-week treatment period. (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Symbicort SMART | 331.8 |
| Symbicort+Terbutaline As Needed | 324.7 |
An as-needed-free day is defined as a night and day with no use of as-needed medication. The mean value from the treatment period was presented here. (NCT00839800)
Timeframe: 52-week treatment period
| Intervention | percentage of as-needed-free days (Mean) |
|---|---|
| Symbicort SMART | 51.4 |
| Symbicort+Terbutaline As Needed | 47.2 |
Asthma exacerbation was defined as deterioration in asthma leading to oral GCS treatment, hospitalization, or ER treatment. Number of asthma exacerbations during 52 weeks treatment was presented here. (NCT00839800)
Timeframe: up to 52 weeks
| Intervention | Asthma exacerbations (Number) |
|---|---|
| Symbicort SMART | 259 |
| Symbicort+Terbutaline As Needed | 363 |
The ratio of the volumes in liters of FEV-1 to Forced vital capacity (FVC). This is reported as percent for each time point., Each time point will be compared.for the two interventions. This expressed as a percentage. (NCT00915538)
Timeframe: 0,5,10,15,30,60,120,240,480,720 minutes
| Intervention | percentage of fev1/fvc (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0 time | 5 minutes | 10 minutes | 15 minutes | 30 minutes | 60 minutes | 120 minutes | 240 minutes | 480 minutes | 720 minutes | |
| Non-Spacer (Conventional) | 75.58 | 79.91 | 81.16 | 80.29 | 80.55 | 81.63 | 81.40 | 82.42 | 80.56 | 80.33 |
| Spacer | 76.13 | 79.08 | 78.55 | 79.08 | 80.17 | 78.05 | 80.94 | 81.56 | 79.95 | 79.93 |
The mean FEV-1 (Forced Expiratory Volume 1 second) for each of the treatments (with and without valved holding chamber) in this crossover design were recorded at BL, 5, 10, 15, 30, 60, 120, 240. 480, 720 minutes (12 hrs) were plotted as a curve and the area under the curve was calculated. The measured results was mean liters/12 hours. (NCT00915538)
Timeframe: BL, 5, 10,15,30,60,120,240,480,720 minutes (12 hrs)
| Intervention | Liters X hours (Mean) |
|---|---|
| Group 1 | 2.77 |
| Group 2 | 2.79 |
Change in the number of as-needed day-time inhalations of medication, defined as the difference in mean value of all available data obtained during treatment period and mean value in run-in period. (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.30 |
Change in the number of as-needed night-time inhalations of medication, calculated as difference in mean value of all available data obtained during treatment period and mean value in run-in period. (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.30 |
The mean percentage of days during treatment period participants used ≥ 3 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 28.25 |
The mean percentage of days during treatment period participants used ≥ 9 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.19 |
Total number of inhalations of Symbicort® 160µg/4.5µg per day during treatment period, defined as the sum of maintenance medication and as-needed medication during night and day time (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | 2.51 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.58 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.74 |
The mean percentage of days during treatment period participants used ≥ 5 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 6.21 |
Participants' emotional functions were scored on a scale of decreasing impairment to emotional function from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) emotion function score were calculated as change from baseline (Week 0) to the treatment period (mean of the scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.77 |
Participants ' responses to environmental stimuli were scored on a scale of decreasing response to environmental stimuli from 1 to 7, in which 1 = maximum response. The change in overall mean AQLQ(S) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.67 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) symptom score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.77 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.58 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) score from baseline were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.70 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -1.18 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) symptom score from baseline were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.59 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.22 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.36 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.24 |
| Oxis Turbuhaler (Active Comparator) | -0.24 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter (L) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 0.0176 |
| Oxis Turbuhaler (Active Comparator) | -0.0324 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 2.55 |
| Oxis Turbuhaler (Active Comparator) | -5.13 |
The change from Run-in period average to Treatment period average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -4.37 |
| Oxis Turbuhaler (Active Comparator) | -2.90 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter (L) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 0.0244 |
| Oxis Turbuhaler (Active Comparator) | -0.0312 |
Scored 0 to 1 (0 = no awakening and 1 = awakening). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Nights with symptoms (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.20 |
| Oxis Turbuhaler (Active Comparator) | -0.15 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 12-week randomization treatment (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | event (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 93 |
| Oxis Turbuhaler (Active Comparator) | 151 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | percentage of participants (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 11.9 |
| Oxis Turbuhaler (Active Comparator) | 16.9 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 104.6 |
| Oxis Turbuhaler (Active Comparator) | 101.5 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 102.2 |
| Oxis Turbuhaler (Active Comparator) | 100.9 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 113.9 |
| Oxis Turbuhaler (Active Comparator) | 111.2 |
The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group. (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.78 |
| Oxis Turbuhaler (Active Comparator) | -0.61 |
Total number of days with COPD exacerbation for each treatment group (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | days (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 653 |
| Oxis Turbuhaler (Active Comparator) | 1098 |
The change from Run-in period average to Treatment period average for each treatment group. (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | inhalations/day (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.51 |
| Oxis Turbuhaler (Active Comparator) | -0.26 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 110.1 |
| Oxis Turbuhaler (Active Comparator) | 108.7 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.34 |
| Oxis Turbuhaler (Active Comparator) | -0.23 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 4.29 |
| Oxis Turbuhaler (Active Comparator) | -4.78 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -3.2 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -1.3 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | beats/minute (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.2 |
| Arm 2 - COPD Standard Therapy | 3.1 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | Percentage of participants (Number) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 20.0 |
| Arm 2 - COPD Standard Therapy | 31.5 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | innhalation/day (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | 0.0 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | event (Number) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 41 |
| Arm 2 - COPD Standard Therapy | 105 |
The change from Run-in period average to 52-week randomization Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter/minute(L/min) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 5.9 |
| Arm 2 - COPD Standard Therapy | 5.7 |
There are 5 alternatives (scored 0 to 4, 0= unaware of any difficulty and 4 =almost constant, present even when resting). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | -0.1 |
There are 5 alternatives (scored 0 to 4, 0= unaware of coughing, 4= never free of cough or need to cough). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | -0.2 |
There are 5 alternatives (scored 0 to 4, 0= no awakening and 4 =did not sleep at all). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.0 |
| Arm 2 - COPD Standard Therapy | -0.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.02 |
| Arm 2 - COPD Standard Therapy | 0.01 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.5 |
| Arm 2 - COPD Standard Therapy | 1.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.03 |
| Arm 2 - COPD Standard Therapy | 0.04 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 1.3 |
| Arm 2 - COPD Standard Therapy | 8.2 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.0 |
| Arm 2 - COPD Standard Therapy | 1.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.243 |
| Arm 2 - COPD Standard Therapy | 0.224 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mEq/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.11 |
| Arm 2 - COPD Standard Therapy | -0.08 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.01 |
| Arm 2 - COPD Standard Therapy | 0.02 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mEq/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -0.6 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.05 |
| Arm 2 - COPD Standard Therapy | 0.00 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.51 |
| Arm 2 - COPD Standard Therapy | -0.64 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Basophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.06 |
| Arm 2 - COPD Standard Therapy | -0.06 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Eosinophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.52 |
| Arm 2 - COPD Standard Therapy | 0.14 |
Mean change from Baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | *10000/μl (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -7.6 |
| Arm 2 - COPD Standard Therapy | -0.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.22 |
| Arm 2 - COPD Standard Therapy | -0.05 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | /microliter(mcl) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 160.8 |
| Arm 2 - COPD Standard Therapy | -184.8 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Lymphocytes (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -5.47 |
| Arm 2 - COPD Standard Therapy | -3.24 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Monocytes (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.29 |
| Arm 2 - COPD Standard Therapy | -0.03 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.003 |
| Arm 2 - COPD Standard Therapy | -0.017 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | *10000/μl (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.86 |
| Arm 2 - COPD Standard Therapy | 0.12 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | beats/minute (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.6 |
| Arm 2 - COPD Standard Therapy | 3.4 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -4.5 |
| Arm 2 - COPD Standard Therapy | -7.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.6 |
| Arm 2 - COPD Standard Therapy | 2.4 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.7 |
| Arm 2 - COPD Standard Therapy | -1.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -30.9 |
| Arm 2 - COPD Standard Therapy | -43.8 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter(L) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.006 |
| Arm 2 - COPD Standard Therapy | 0.010 |
The change from Run-in period average to 52-week randomization Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter/minute(L/min) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 2.7 |
| Arm 2 - COPD Standard Therapy | 5.2 |
The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. (NCT01070784)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 104.25 |
| Arm 2 - COPD Standard Therapy | 98.43 |
The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. (NCT01070784)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 102.51 |
| Arm 2 - COPD Standard Therapy | 100.04 |
The change from run-in period and daily during 52-week randomization treatment average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -2.03 |
| Arm 2 - COPD Standard Therapy | -0.42 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter(L) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.017 |
| Arm 2 - COPD Standard Therapy | 0.006 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Neutrophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 5.78 |
| Arm 2 - COPD Standard Therapy | 2.92 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. The maximum FEV1 value was defined as the largest observed FEV1 value recorded during each 12-hour serial spirometry procedure. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.833 |
| BUD 160/FM 4.5 | 1.889 |
| BUD 160/FM 9.0 | 1.884 |
| BUD 160 | 1.777 |
| BUD 160/ Foradil 12.0 | 1.892 |
The amount of formoterol excreted unchanged in urine over the 12-hour period after administration [Ae(0-12h)] was calculated from the concentration of formoterol in urine multiplied by the total volume of urine collected. Volume was determined from the weight of the collected urine times an assumed urine density of 1020 g/L. The data for six patients who did not have measurable formoterol in their urine on the Foradil 12 μg treatment day was excluded from the analysis. All other urine concentrations below the lower limit of quantification were set to zero. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: 0 to 12 hours
| Intervention | pmol (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 192.0 |
| BUD 160/FM 4.5 | 366.3 |
| BUD 160/FM 9.0 | 740.6 |
| BUD 160/ Foradil 12.0 | 658.7 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was obtained from the full expiratory flow-volume-time curve. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. Twelve-hour serial FEV1 was calculated through an AUC determination and then divided by time, so that the final value is expressed in liters. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.546 |
| BUD 160/FM 4.5 | 1.594 |
| BUD 160/FM 9.0 | 1.603 |
| BUD 160 | 1.489 |
| BUD 160/ Foradil 12.0 | 1.603 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. The FEV1 value at 12 hours after dosing was taken as the 12-hour measurement (720 minutes) from the serial spirometry. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: 12 hours after dosing
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.641 |
| BUD 160/FM 4.5 | 1.692 |
| BUD 160/FM 9.0 | 1.731 |
| BUD 160 | 1.626 |
| BUD 160/ Foradil 12.0 | 1.709 |
"Asthma symptoms scores reported as measure of FEV1 - Forced Expiratory Volume in one second~FEV1 is given which is a standard outcome in asthma studies and is validated by the NIH (NHLBI)~FEV1 of less than 80 is indicative of severe asthma, 80-90 is moderate asthma, over 90 is mild asthma~http://www.med.umich.edu/1info/FHP/practiceguides/asthma/EPR-3_pocket_guide.pdf" (NCT01218399)
Timeframe: 1 week
| Intervention | % FEV1 (Mean) |
|---|---|
| Symbicort | 90 |
| Budesonide | 88 |
Number of adverse events as per MEDRA terms (NCT01218399)
Timeframe: 1 week
| Intervention | Number adverse events (Number) |
|---|---|
| Symbicort | 0 |
| Budesonide | 0 |
The total score is calculated as sum of the morning and evening scores of each day and the treatment period mean score is defined as the mean of all total score recorded during the 12-week treatment period. Trt Avg=Mean total score of double-blind period values.(day/night score ranges from 0 to 3; 0=no asthma symptoms; 3= unable to do normal activities (or to sleep) due to asthma). Higher score represents worse outcome. (NCT01360021)
Timeframe: Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks
| Intervention | Asthma score on a scale of 0 to 3 (Mean) | |
|---|---|---|
| Baseline | Treatment Average (Trt Avg) | |
| Budesonide | 2.12 | 2.02 |
| Symbicort BA MDI | 2.04 | 1.68 |
| Symbicort pMDI | 1.92 | 1.45 |
Descriptive statistics for post-dose FEV1 (L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization. (NCT01360021)
Timeframe: 60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg
| Intervention | Liter (Geometric Mean) | |||||
|---|---|---|---|---|---|---|
| Baseline | Week 0 | Week 3 | Week 7 | Week 12 | Treatment Average | |
| Budesonide | 2.12 | 2.28 | 2.30 | 2.33 | 2.30 | 2.30 |
| Symbicort BA MDI | 2.09 | 2.49 | 2.52 | 2.59 | 2.52 | 2.53 |
| Symbicort pMDI | 1.97 | 2.35 | 2.34 | 2.35 | 2.39 | 2.37 |
Descriptive statistics for predose FEV1(L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization. (NCT01360021)
Timeframe: Pre AM dose in clinic visits at baseline, and week 3, 7, 12 and Trt Avg
| Intervention | Liters (Geometric Mean) | ||||
|---|---|---|---|---|---|
| Baseline | Week 3 | Week 7 | Week 12 | Average of treatment period | |
| Budesonide | 2.12 | 2.22 | 2.25 | 2.23 | 2.23 |
| Symbicort BA MDI | 2.09 | 2.32 | 2.40 | 2.34 | 2.34 |
| Symbicort pMDI | 1.97 | 2.12 | 2.11 | 2.17 | 2.15 |
The percentage of days with no awakenings due to asthma. Baseline= Mean % awakening-free nights during run-in period ; Trt Avg=Mean % awakening-free nights during double-blind period. (NCT01360021)
Timeframe: Recorded 6:00 - 11:00 AM for 14 weeks
| Intervention | Percentage of days with no awakenings (Mean) | |
|---|---|---|
| Baseline | Treatment Average (Trt Avg) | |
| Budesonide | 81.59 | 84.62 |
| Symbicort BA MDI | 78.54 | 83.73 |
| Symbicort pMDI | 78.76 | 89.93 |
(NCT01360021)
Timeframe: Recorded morning upon rising and evening before sleep for 14 weeks
| Intervention | L/Min (Mean) | |||
|---|---|---|---|---|
| Morning Peak expiratory flow (Baseline) | Evening Peak expiratory flow (Baseline) | Evening Peak expiratory flow (Treatment Average) | Morning Peak expiratory flow (Treatment Average) | |
| Budesonide | 360.46 | 367.64 | 348.94 | 343.59 |
| Symbicort BA MDI | 357.95 | 364.61 | 379.96 | 376.28 |
| Symbicort pMDI | 335.70 | 347.86 | 362.99 | 353.69 |
Total daily rescue medication use is calculated as the sum of morning and evening use each day and averaged over the 12 weeks treatment periods to calculate the treatment period mean. Baseline= Mean rescue medication used during run-in period ; Trt Avg=Mean rescue medication used during double-blind period. (NCT01360021)
Timeframe: Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks
| Intervention | Inhalations/24 hrs (Mean) | |
|---|---|---|
| Baseline | Treatment Average (Trt Avg) | |
| Budesonide | 2.65 | 2.34 |
| Symbicort BA MDI | 2.55 | 1.81 |
| Symbicort pMDI | 2.19 | 1.26 |
Change in Cough symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.311 |
| Spiriva | -0.169 |
Change in Sputum symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.216 |
| Spiriva | -0.094 |
Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms (NCT01397890)
Timeframe: Whole treatment period of 12 weeks
| Intervention | exacerbations/participant/12 weeks (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 0.182 |
| Spiriva | 0.307 |
Ratio of post-dose FEV1 at 5 minutes to baseline value (NCT01397890)
Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.128 |
| Spiriva | 1.045 |
Ratio of post-dose FEV1 at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.164 |
| Spiriva | 1.072 |
Ratio of post-dose FVC at 5 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.096 |
| Spiriva | 1.044 |
Ratio of post-dose FVC at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.116 |
| Spiriva | 1.059 |
Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 17.412 |
| Spiriva | 0.220 |
Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment, up to 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 23.379 |
| Spiriva | -3.049 |
Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period of 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 15.880 |
| Spiriva | -2.591 |
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.050 |
| Spiriva | 1.006 |
Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.032 |
| Spiriva | 1.013 |
Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.042 |
| Spiriva | 1.022 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 13.405 |
| Spiriva | -0.182 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment, up to 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 15.753 |
| Spiriva | -4.550 |
Change in pre-dose morning PEF from run-in period to whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period of 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 12.271 |
| Spiriva | -5.198 |
Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.457 |
| Spiriva | -0.082 |
Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.750 |
| Spiriva | -0.082 |
Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.685 |
| Spiriva | -0.134 |
Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.113 |
| Spiriva | 0.011 |
Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.174 |
| Spiriva | 0.062 |
Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.241 |
| Spiriva | -0.010 |
Ratio of post-dose IC at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.154 |
| Spiriva | 1.087 |
Change in breathing symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.372 |
| Spiriva | -0.110 |
Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms (NCT01415518)
Timeframe: Whole treatment period (12 weeks)
| Intervention | exacerbations/12 weeks (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 0.069 |
| Ipratropium + Theophylline SR | 0.121 |
Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.441 |
| Ipratropium + Theophylline SR | -0.248 |
Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.332 |
| Ipratropium + Theophylline SR | -0.124 |
Ratio of post-dose FEV1 at 5 minutes to baseline value (NCT01415518)
Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.179 |
| Ipratropium + Theophylline SR | 1.106 |
Ratio of post-dose FEV1 at 60 minutes to baseline value (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.219 |
| Ipratropium + Theophylline SR | 1.142 |
Ratio of post-dose FVC at 5 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.170 |
| Ipratropium + Theophylline SR | 1.120 |
Ratio of post-dose FVC at 60 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.192 |
| Ipratropium + Theophylline SR | 1.148 |
Ratio of post-dose IC at 60 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.163 |
| Ipratropium + Theophylline SR | 1.120 |
Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 25.993 |
| Ipratropium + Theophylline SR | 1.670 |
Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 36.612 |
| Ipratropium + Theophylline SR | 5.100 |
Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 26.507 |
| Ipratropium + Theophylline SR | -0.662 |
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value (NCT01415518)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.079 |
| Ipratropium + Theophylline SR | 1.009 |
Ratio of pre-dose FVC (Forced Vital Capacity) to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.072 |
| Ipratropium + Theophylline SR | 1.030 |
Ratio of pre-dose IC (Inspiratory Capacity) to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.068 |
| Ipratropium + Theophylline SR | 1.032 |
Change in pre-dose morning PEF from run-in period to first week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 24.393 |
| Ipratropium + Theophylline SR | 3.257 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 23.135 |
| Ipratropium + Theophylline SR | -2.038 |
Change in pre-dose morning PEF from run-in period to whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 21.021 |
| Ipratropium + Theophylline SR | -2.023 |
Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.440 |
| Ipratropium + Theophylline SR | -0.097 |
Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.398 |
| Ipratropium + Theophylline SR | -0.101 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks)
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.404 |
| Ipratropium + Theophylline SR | -0.061 |
change in the number of inhalations of reliever medication during day from run-in to the first week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.124 |
| Ipratropium + Theophylline SR | -0.002 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks)
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.086 |
| Ipratropium + Theophylline SR | 0.020 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.078 |
| Ipratropium + Theophylline SR | -0.023 |
Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.507 |
| Ipratropium + Theophylline SR | -0.229 |
Percent of days with no asthma symptoms during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. (NCT01444430)
Timeframe: Daily up to 26 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 81.1 |
| Budesonide | 76.8 |
Percent of days with activity limitation due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. (NCT01444430)
Timeframe: Daily up to 26 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 19.7 |
| Budesonide | 19.1 |
Number of participants experiencing discontinuation of investigational product due to a protocol defined asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. (NCT01444430)
Timeframe: Up to 26 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 53 |
| Budesonide | 71 |
Number of participants experiencing an event in the composite endpoint (asthma-related death, asthma-related intubation or asthma-related hospitalization), using events adjudicated and confirmed by the Joint Adjudication Committee. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. (NCT01444430)
Timeframe: Up to 27 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 43 |
| Budesonide | 40 |
"The outcome variable for ACQ6 was the difference between the average of values recorded during the treatment period (day 28, day 84 and day 182) and the baseline measure. Analysis of covariance (ANCOVA) model, including the fixed factors of treatment and strata by incoming control/asthma treatment and baseline ACQ6 as covariate was used to compare Symbicort and budesonide.~The asthma control questionnaire, ACQ6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions." (NCT01444430)
Timeframe: baseline, day 28, day 84, day 182
| Intervention | ACQ6 overall score change from baseline (Least Squares Mean) |
|---|---|
| Symbicort | -0.70 |
| Budesonide | -0.62 |
Mean number of puffs of rescue medication per day (24 hours) during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. (NCT01444430)
Timeframe: Daily up to 26 weeks
| Intervention | Inhalations/day (Least Squares Mean) |
|---|---|
| Symbicort | 0.8 |
| Budesonide | 0.9 |
Percent of nights with awakening(s) due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide. (NCT01444430)
Timeframe: Daily up to 26 weeks
| Intervention | Percentage of nights (Least Squares Mean) |
|---|---|
| Symbicort | 4.0 |
| Budesonide | 4.7 |
Number of participants experiencing an event included in the definition of asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated. (NCT01444430)
Timeframe: Up to 26 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 539 |
| Budesonide | 633 |
Improvement in FEV1 compared to baseline levels. (NCT01787097)
Timeframe: Baseline and 2 hours post inhalation
| Intervention | mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | 160 |
| Symbicort® Total Dose 400ug/12ug | 120 |
| Symbicort® Total Dose 800ug/24ug: | 200 |
| Pulmicort 800ug | 52 |
Sputum TNF-alpha levels obtained from induced sputum compared to screening visit. (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -4.8 |
| Symbicort® Total Dose 400ug/12ug | -5.7 |
| Symbicort® Total Dose 800ug/24ug | -7.8 |
| Pulmicort 800ug | -9.4 |
Enzyme immunosorbent assay system (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | Fold activation (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | 1.1 |
| Symbicort® Total Dose 400ug/12ug | 1.8 |
| Symbicort® Total Dose 800ug/24ug | 2.3 |
| Pulmicort 800ug | 2.1 |
Changes in CXCL8 concentrations in sputum compared to screening visit. (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | ng/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -0.04 |
| Symbicort® Total Dose 400ug/12ug | -2.1 |
| Symbicort® Total Dose 800ug/24ug | -2.2 |
| Pulmicort 800 | -1.5 |
Changes in IL-6 Levels in the sputum supernatant compared to screening visit (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -29 |
| Symbicort® Total Dose 400ug/12ug | -14 |
| Symbicort® Total Dose 800ug/24ug | -28 |
| Pulmicort 800 | -29 |
Swab samples were collected by a qualified professional. (NCT01803555)
Timeframe: Baseline, Week 4, Week 8, Week 12
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Baseline | Week 4 | Week 8 | Week 12 | |
| BF Spiromax | 1 | 0 | 0 | 1 |
| Symbicort Turbohaler | 0 | 0 | 0 | 1 |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline was defined as the average value of the recorded (nonmissing) assessments over the 7 days prior to randomization. For postdose weekly average of evening PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of evening PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. (NCT01803555)
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| BF Spiromax | 18.661 |
| Symbicort Turbohaler | 21.740 |
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. (NCT01803555)
Timeframe: Baseline up to Week 12
| Intervention | Participants (Count of Participants) |
|---|---|
| BF Spiromax | 117 |
| Symbicort Turbohaler | 106 |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. (NCT01803555)
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)
| Intervention | liters (L)/minute (min) (Least Squares Mean) |
|---|---|
| BF Spiromax | 18.839 |
| Symbicort Turbohaler | 21.796 |
Examinations were performed by a qualified professional. (NCT01803555)
Timeframe: Baseline, Week 4, Week 8, Week 12
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Baseline | Week 4 | Week 8 | Week 12 | |
| BF Spiromax | 0 | 1 | 1 | 2 |
| Symbicort Turbohaler | 0 | 0 | 2 | 3 |
End of study average is defined as the average of available records from 7 days before up to and including the day prior to withdrawal from study or Week 12, minus the baseline measurement at randomization, for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Number of reliever medication use (Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | -0.7 |
| Symbicort pMDI 80/2.25 ug | -1.1 |
| Budesonide pMDI 80 ug | -0.7 |
"Study period average is defined as the average of the post-baseline values during the study taken after first dose of investigational product up to and including withdrawal from study or Week 12, minus the baseline assessment at randomization, for patients who remain in the study (irrespective of whether IP has been discontinued).~The PAQLQ(S) is a 23-item patient-reported questionnaire, each one reported on a 7-point scale (e.g. 1 = extremely bothered/all of the time; 7 = not bothered/none of the time). The PAQLQ(S) generates an overall score, as well as 3 domain scores: activity limitations (5 items), symptoms (10 items) and emotional function (8 items). The overall score will be calculated as the mean of the responses to each of the 23 questions (ie the range of 1-7, where higher scores indicate better quality of life). If any of the domain scores are missing, no total score will be calculated." (NCT02091986)
Timeframe: Week 0 (baseline), week 4, week 8, week 12
| Intervention | unit on a scale (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.46 |
| Symbicort pMDI 80/2.25 ug | 0.53 |
| Budesonide pMDI 80 ug | 0.62 |
15 min Post-dose FEV1 is defined as the 15 min post-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.25 |
| Symbicort pMDI 80/2.25 ug | 0.19 |
| Budesonide pMDI 80 ug | 0.15 |
1h post-dose FEV1 is defined as the 1-hour post-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.28 |
| Symbicort pMDI 80/2.25 ug | 0.24 |
| Budesonide pMDI 80 ug | 0.17 |
1h post-dose FVC is defined as the 1-hour post-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.22 |
| Symbicort pMDI 80/2.25 ug | 0.16 |
| Budesonide pMDI 80 ug | 0.17 |
1h post-dose PEF is defined as the 1-hour post-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters per minute (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 57.04 |
| Symbicort pMDI 80/2.25 ug | 41.14 |
| Budesonide pMDI 80 ug | 31.57 |
Pre-dose FEF25-75 is defined as the pre-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters per minute (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.12 |
| Symbicort pMDI 80/2.25 ug | 0.13 |
| Budesonide pMDI 80 ug | 0.09 |
Pre-dose FEV1 is defined as the pre-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.11 |
| Symbicort pMDI 80/2.25 ug | 0.10 |
| Budesonide pMDI 80 ug | 0.09 |
Pre-dose FVC is defined as the pre-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.11 |
| Symbicort pMDI 80/2.25 ug | 0.11 |
| Budesonide pMDI 80 ug | 0.13 |
Pre-dose PEF is defined as the pre-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters per minute (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 27.73 |
| Symbicort pMDI 80/2.25 ug | 15.86 |
| Budesonide pMDI 80 ug | 16.01 |
Number of patients that experienced an asthma exacerbation that required either emergency room treatment, hospitalization, systemic steroids, or an increase in, or additional asthma maintenance medication, during the study. (NCT02091986)
Timeframe: Week 0 (baseline) up to Week 12
| Intervention | Partcicipants (Number) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 9 |
| Symbicort pMDI 80/2.25 ug | 12 |
| Budesonide pMDI 80 ug | 12 |
"End of study average is defined as the average of available records from 7 days before up to and including the day prior to withdrawal from study or Week 12, minus the baseline measurement at randomization, for patients who remain in the study (irrespective of whether IP has been discontinued).~Patient to record his/her asthma symptom score twice daily. The following rating scales are to be used: 0 = None; no symptoms of asthma~= Mild symptoms; awareness of asthma symptoms and/or signs that are easily tolerated~= Moderate symptoms, asthma symptoms with some discomfort, causing some interference with daily activities or sleep~= Severe symptoms; incapacitating asthma symptoms and/or signs, with inability to perform daily activities or to sleep~Total asthma symptom score is derived as the sum of the daytime score plus the score from the previous nighttime, ie possible range (0 to 6)." (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | -0.5 |
| Symbicort pMDI 80/2.25 ug | -0.6 |
| Budesonide pMDI 80 ug | -0.4 |
1h post-dose FEF25-75 is defined as the 1-hour post-dose measurement taken at Week 12 minus the pre dose measurement taken at randomization for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Liters per second (Least Squares Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | 0.55 |
| Symbicort pMDI 80/2.25 ug | 0.47 |
| Budesonide pMDI 80 ug | 0.23 |
End of study average is defined as the percentage of nighttime awakenings due to asthma symptoms from 6 days before up to and additionally including the morning of withdrawal from study or Week 12, minus the baseline measurement at randomization, for patients who remain in the study (irrespective of whether IP has been discontinued). (NCT02091986)
Timeframe: Week 0 (baseline), Week 12
| Intervention | Percentage of nighttime awakenings (Mean) |
|---|---|
| Symbicort pMDI 80/4.5 ug | -14.0 |
| Symbicort pMDI 80/2.25 ug | -17.3 |
| Budesonide pMDI 80 ug | -13.0 |
"Use of rescue medication is a measure of symptoms that need to be treated with a short-acting bronchodilator.~The average daily use across the observation period was used for analysis. Change from baseline was summarized and compared between two arms using a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | puffs/day (Mean) |
|---|---|
| Symbicort pMDI | 0.135 |
| Formoterol Turbuhaler | 0.343 |
"Nighttime awakening due to COPD symptoms correspond to the severity of nocturnal symptoms from COPD.~The average number of awakening per night over the treatment period was analyzed. It was derived as the number of night with awakening divided by the total number of nights with data in the recording period. Change from baseline period on awakening was summarized and compared between two arms using a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | awakening/night (Mean) |
|---|---|
| Symbicort pMDI | -0.007 |
| Formoterol Turbuhaler | 0.021 |
"The number of patients who developed moderate or severe COPD exacerbation during treatment period were reported. Cox proportional hazards regression model was fitted to data to compare the two treatment arms .~The hazard ratio and 95% CI were estimated." (NCT02157935)
Timeframe: From randomzation to EoT W 26
| Intervention | Participants (Number) |
|---|---|
| Symbicort pMDI | 171 |
| Formoterol Turbuhaler | 204 |
FEV1 from pre-dose spirometry is a measurement of lung function. The change from baseline on pre-dose FEV1 was summarized and compared between Symbicort and Formoterol groups using a mixed model. (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | L (Mean) |
|---|---|
| Symbicort pMDI | 0.008 |
| Formoterol Turbuhaler | -0.025 |
"The annual COPD exacerbation rate was analyzed and compared between two arms.~Annual exacerbation rate for each subject is defined as number of exacerbations divided by duration of randomized treatment period in years.~The annual COPD exacerbation rate of Symbicort group was compared with annual rate of Formoterol group. The rate ratio of Symbicort vs. Formoteroal was assessed by a negative binomial model.~Exacerbations, that met the modified Anthonisen criteria and duration ≥2 days were classified as moderate and severe exacerbations.~Moderate exacerbation: treatment of symptoms with systemic corticosteroids (≥3 days) and/or antibiotics.~Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting)." (NCT02157935)
Timeframe: Randomization at Week 0 to End of Treatment (EoT) W 26
| Intervention | COPD exacerbations per year (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.85 |
| Formoterol Turbuhaler | 1.12 |
"SGRQ is a standardized, self-administered tool for measuring impaired health and perceived wellbeing in respiratory diseases; a validated electronic version of the questionnaire in the relevant validated languages was used in this study.~The questionnaire contains 50 items divided into three dimensions (Symptoms, Activity and Impact).~Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100:~zero (0) score indicating no impairment of quality of life.~The total SGRQ score ranging from 0 to 100 is a summary score utilizing responses to all items calculated using weights attached to each item of the questionnaire.~Higher scores indicate poorer health and change of 4 units in the SGRQ has been determined to be the threshold for a clinically relevant change in health status.~The change from baseline was statistically summarized and compared between two arms in a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | scores on a scale (Mean) |
|---|---|
| Symbicort pMDI | -0.855 |
| Formoterol Turbuhaler | 0.442 |
"SRaw = Specific airway resistance: also called volumic airway resistance. sRaw is a corrected index (Raw multiplied by thoracic gas volume) that describes airway behaviour regardless of lung volume. Normal values of sRaw in adult subjects have never been formally defined.~sRaw is the product of Functional Residual Capacity (FRC) and Airways Resistance (Raw) and can be calculated from the relationship of plethysmographic box pressure (Pbox) to flow during spontaneous breathing.~sRaw can be derived from the tangent of the slope of box Pressure/Flow. Since Raw has a strong inverse relationship to lung volume, sRaw provides a relatively stable index with which to distinguish effects of disease from those of growth and development. sRaw is significantly increased in asthmatic patients, in those with wheezing disorders, and cystic fibrosis. It has also been shown to be a useful outcome measure for bronchodilator responsiveness studies." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | kPas (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 1.668 | 1.223 | -0.445 |
| Z7200 | 1.656 | 1.137 | -0.519 |
"Raw = Airway resistance. It is defined as the change in transpulmonary pressure (proximal airway pressure minus the alveolar pressure) required to produce a unit flow of gas through the airways of the lung.~Are considered as normal all values up to 2.8 kPas/L" (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | kPas/L (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 0.411 | 0.276 | -0.135 |
| Z7200 | 0.398 | 0.292 | -0.106 |
FRC = Functional Residual Capacity. It is the volume in the lungs at the end of passive expiration. It is determined by opposing forces of the expanding chest wall and the elastic recoil of the lung. A normal FRC = 1.7 to 3.5 L. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Liters (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 3.685 | 3.498 | -0.187 |
| Z7200 | 3.661 | 3.485 | -0.176 |
MEF25 = Maximal Expiratory Flow at 25% of Forced Vital Capacity (FVC). This parameter is linked to the pathology/obstruction of small airways. Patients with airway obstruction frequently exhibit a marked decrease in MEF25. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | L/s (Mean) | ||
|---|---|---|---|
| predose | postdose | change from pre-dose to postdose | |
| Symbicort Turbohaler | 0.653 | 0.818 | 0.164 |
| Z7200 | 0.700 | 0.873 | 0.173 |
The patients' inhalation profile was assessed using a respiration belt. The inhalation profile through device was to be recorded at the moment of study drug administration. Respiratory belts are useful in measuring changes in thoracic or abdominal circumference during respiration. These measurements can indicate inhalation, expiration and breathing strength and can be used to derive breathing rate and characterize breathing patterns (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Liters (Mean) |
|---|---|
| Z7200 | 2.565 |
| Symbicort Turbohaler | 2.366 |
"VAS = Visual Analogue Scale. A VAS is typically scored by measuring the distance from the bottom of the scale (or left side if oriented horizontally) (in this case after the walk test) to the level indicated by the subject. VAS is typically represented as a vertical or horizontal line, usually 100 millimeters (mm) in length, with descriptors positioned at the extremes of the scale. These extremes go from not breathless at all/no shortness of breath at the bottom or at the far left of the line, to shortness of breath as bad as can be on the top or on the right of the line, depending on the patient's opinion." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | percentage of value (Mean) |
|---|---|
| Z7200 | 21.450 |
| Symbicort Turbohaler | 15.850 |
6MWT = 6 Minutes Walk Test (in meters). The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The longer the walk in that timespan, the better the outcome. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | meters (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 583.789 | 598.158 | 14.368 |
| Z7200 | 577.789 | 581.789 | 4.000 |
"The Total Airway Resistance refers to degree of resistance to the flow of air through the respiratory tract during inspiration and expiration. The degree of resistance depends on many things, particularly the diameter of the airway and whether flow is laminar or turbulent. The higher the resistance, the worse the outcome.~In healthy men and women values range between 0.22 to 0.25 kPa/l." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | kPas/L (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 0.037 | 0.026 | -0.011 |
| Z7200 | 0.034 | 0.025 | -0.008 |
"PEF = Peak Expiratory Flow: is the maximum flow rate generated during a forceful exhalation, starting from full lung inflation.~PEF rate primarily reflects large airway flow and depends on the voluntary effort and muscular strength of the patient.~Normal adult peak expiratory flow ranges between around 400 and 700 liters per minute, although in older it can be lower." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | L/s (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 7.465 | 7.883 | 0.419 |
| Z7200 | 7.593 | 7.912 | 0.319 |
"VAS = Visual Analogue Scale. A VAS is typically scored by measuring the distance from the bottom of the scale (or left side if oriented horizontally) (In this case before the walk test) to the level indicated by the subject. VAS is typically represented as a vertical or horizontal line, usually 100 millimeters (mm) in length, with descriptors positioned at the extremes of the scale. These extremes go from not breathless at all/no shortness of breath at the bottom or at the far left of the line, to shortness of breath as bad as can be on the top or on the right of the line, depending on the patient's opinion.~measure of the difference in dyspnoea before and after treatment" (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | units on a scale (Mean) |
|---|---|
| Z7200 | 19.550 |
| Symbicort Turbohaler | 8.150 |
"FVC = Forced Vital Capacity: is the total amount of air exhaled during the FEV test.~Values of between 80% and 120% of the average value are considered normal." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Liters (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 4.311 | 4.328 | 0.018 |
| Z7200 | 4.317 | 4.384 | 0.066 |
To evaluate the particle deposition in the lungs, the Computational Fluid Dynamic (CFD) was used. With CFD, based on the computed tomography (CT) derived geometries of the airways, it is possible to measure the resistance of all airways or subdivisions such as the smaller airways starting from the 3rd bifurcation onwards. The three-dimensional (3D) reconstruction in this CT-based imaging technique allows for an accurate measurement of local volume changes in the central and peripheral airways after the administration of the product. The increased sensitivity of this technique makes it possible to detect changes in airway caliber in early stages of asthma. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Count of Particles (Mean) | |
|---|---|---|
| Budesonide | Formoterol | |
| Symbicort Turbohaler | 17306552 | 425671 |
| Z7200 | 776339324 | 80448811 |
"FEV1/FVC ratio = Tiffeneau Index. It is a calculated ratio use to diagnose obstructive and restrictive lung disease. It represents the proportion of a patient's vital capacity that he/she is able to expire in the first second of forced expiration to the full forced vital capacity. The result of this ratio is expressed as FEV1%.~Normal values are approximately 75%." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | FEV1% (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 66.800 | 70.600 | 3.800 |
| Z7200 | 67.200 | 70.600 | 3.400 |
"FEV1 = Forced Expiratory Volume in one second. Forced expiratory volume is the most important measurement of lung function. It measures how much air a person can exhale during a forced breath. The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath.~Values of between 80% and 120% of the average value are considered normal." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Liters (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 2.905 | 3.058 | 0.153 |
| Z7200 | 2.935 | 3.112 | 0.178 |
"Borg category (C) ratio (R) 10 scale = The original Borg CR10 Scale is used to measure the intensity of dyspnoea and fatigue during an exercise (in this case before the walk test). The original one was referred to as a numerical category scale going from 0 to 10. The top of the scale, 0 or nothing at all, means no breathlessness at all.~The bottom of the scale, 10 or maximal, means the most severe breathlessness that patients have ever experienced or could imagine experiencing." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | score on a scale (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 0.670 | 0.820 | 0.150 |
| Z7200 | 0.805 | 0.935 | 0.130 |
"Borg category (C) ratio (R) 10 scale = The original Borg CR10 Scale is used to measure the intensity of dyspnoea and fatigue during an exercise (in this case after the walk test). The original one was referred to as a numerical category scale going from 0 to 10. The top of the scale, 0 or nothing at all, means no breathlessness at all.~The bottom of the scale, 10 or maximal, means the most severe breathlessness that patients have ever experienced or could imagine experiencing." (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | score on a scale (Mean) | ||
|---|---|---|---|
| predose | postdose | change from pre-dose | |
| Symbicort Turbohaler | 1.580 | 1.375 | -0.205 |
| Z7200 | 1.945 | 1.820 | -0.125 |
TLC = Total Lung Capacity. It is the volume of air in the lungs upon the maximum effort of inspiration. Among healthy adults, the average lung capacity is about 6 liters. Age, gender, body composition, and ethnicity are factors affecting the different ranges of lung capacity among individuals. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | Liters (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 7.008 | 6.957 | -0.051 |
| Z7200 | 7.003 | 7.007 | 0.004 |
MEF50 = Maximal Expiratory Flow at 50% of Forced Vital Capacity (FVC). MEF50 is the flow where half of forced vital capacity (FVC) remains to be exhaled. Also this parameter is linked to the pathology/obstruction of small airways. Patients with airway obstruction frequently exhibit a marked decrease in MEF50. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | L/s (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose and postdose | |
| Symbicort Turbohaler | 2.350 | 2.767 | 0.416 |
| Z7200 | 2.439 | 2.878 | 0.440 |
The Total Airway Volume is the amount of air that can be inhaled or exhaled during one respiratory cycle. This depicts the functions of the respiratory centers, respiratory muscles and the mechanics of the lung and chest wall. The higher the volume, the better the outcome. (NCT02227394)
Timeframe: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
| Intervention | mL (Mean) | ||
|---|---|---|---|
| predose | postdose | change from predose to postdose | |
| Symbicort Turbohaler | 48.577 | 50.831 | 2.255 |
| Z7200 | 49.033 | 51.101 | 2.068 |
FEV1 is the maximal amount of air that can be forcefully exhaled in one second. FEV1 AUC (0 to 10h) was measured at beginning of each TP. AUC was derived using values observed at the following timepoints: 0 minute (pre-morning dosing), 5 minutes (m), 15m, 30m, 1, 2, 5, and 10h; post morning dosing FEV1 values on D1 of each TP. Pre-dose was taken as, 0h timepoint on the visit of interest, and all subsequent timepoints were calculated relative to that timepoint. FEV1 AUC was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific(PS) BL, treatment group and period, with participant as random effect. (NCT02233803)
Timeframe: (0-10 h) at D1 (each TP)
| Intervention | L*hrs (Least Squares Mean) |
|---|---|
| NEUMOTEROL 400 | 24.573 |
| SYMBICORT FORTE | 23.593 |
FEV1 is maximal amount of air, forcefully exhaled in one second. Trough FEV1 is defined as morning prebronchodilator and predose: 12 hours (h) after last evening dose D28 at end of each TP. Measured by spirometer in morning, before using bronchodilator and pre-dosing at wk1 D1 and wk4 D29 of each TP and test was performed within 30 minutes prior to dosing. Change from BL was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific (PS) BL, treatment group and period, with participant as random effect. PS BL value is pre-dose assessment collected on D1 of each TP. SL BL is arithmetic mean of PS BL values of participant. If only one of PS BL value is missing for participant, SL BL took value of other BL. If both PS BL values were missing, SL BL was set to missing. Period level BL=PS BL - associated SL BL. (NCT02233803)
Timeframe: BL (D1) and D29 (each TP)
| Intervention | Litre (L) (Least Squares Mean) |
|---|---|
| NEUMOTEROL 400 | 0.194 |
| SYMBICORT FORTE | 0.150 |
ACT was basically a five item questionnaire, to measure participant's asthma control. It comprised of five possible answers to each question, associated with a score of 1 to 5 (1=poor control and 5=good control), wherein the scores from each question were summed to give an overall score (5=poor control and 25=complete control). ACT was recommended during each visit and was completed by the participant before any procedures were performed, avoiding any influence of the participants response. Change from BL was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific(PS) BL, treatment group and period, with participant as random effect. PS BL value, is pre-dose assessment collected on D1 of each TP. SL BL, is arithmetic mean of PS BL values of participant. Participants with an ACT below 15 were excluded from the study. (NCT02233803)
Timeframe: BL up to W4 (each TP)
| Intervention | units on scale (Least Squares Mean) |
|---|---|
| NEUMOTEROL 400 | 1.6 |
| SYMBICORT FORTE | 1.0 |
"Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1980 |
| Treatment B | 1450 |
| Treatment C | 1900 |
| Treatment D | 1410 |
"Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 324 |
| Treatment B | 174 |
| Treatment C | 342 |
| Treatment D | 193 |
"Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.08 |
| Treatment B | 0.08 |
| Treatment C | 0.08 |
| Treatment D | 0.08 |
"Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.08 |
| Treatment B | 0.25 |
| Treatment C | 0.08 |
| Treatment D | 0.25 |
"Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 9.57 |
| Treatment B | 9.33 |
| Treatment C | 10.09 |
| Treatment D | 9.15 |
"Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 2.90 |
| Treatment B | 2.94 |
| Treatment C | 2.79 |
| Treatment D | 2.80 |
Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 11.9 |
| Treatment B | 9.53 |
| Treatment C | 12.4 |
| Treatment D | 10.6 |
Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 1040 |
| Treatment B | 482 |
| Treatment C | 1090 |
| Treatment D | 542 |
"FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath.~FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.~Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.~But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | ratio (Mean) |
|---|---|
| Treatment A | 3.7 |
| Treatment B | 3.6 |
| Treatment C | 3.2 |
| Treatment D | 3.8 |
"PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together. But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | L/min (Mean) |
|---|---|
| Treatment A | 22.2 |
| Treatment B | 20.5 |
| Treatment C | 24.8 |
| Treatment D | 19.2 |
"FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.~and Symbicort 2, together. Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.~But some subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | liters (Mean) |
|---|---|
| Treatment A | 0.2 |
| Treatment B | 0.2 |
| Treatment C | 0.2 |
| Treatment D | 0.2 |
"Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 47.4 |
| Treatment B | 40.1 |
| Treatment C | 44.7 |
| Treatment D | 34.5 |
"Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 56.0 |
| Treatment B | 49.8 |
| Treatment C | 54.5 |
| Treatment D | 45.2 |
"Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1870 |
| Treatment B | 1360 |
| Treatment C | 1810 |
| Treatment D | 1330 |
"Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Least Squares Mean) |
|---|---|
| Treatment A | 3.85 |
| Treatment B | 3.12 |
| Treatment C | 4.00 |
| Treatment D | 3.35 |
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12 and Week 24. Change from Baseline (BL) was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). The maximum post BL values have been presented. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | g/L (Mean) | |||
|---|---|---|---|---|
| Week 24, Albumin, n=839,787 | Maximum post BL, Albumin, n=888,866 | Week 24, Protein, n=839,787 | Maximum post BL, Protein, n=888,866 | |
| BUD/FOR 400/12 µg | -0.5 | 0.2 | -1.0 | 0.1 |
| FF/UMEC/VI 100/62.5/25 µg | -0.7 | 0.1 | -0.6 | 0.4 |
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | g/L (Mean) | |||
|---|---|---|---|---|
| Week 52, Albumin, n=181,174 | Maximum post BL,Albumin, n=207,214 | Week 52, Protein, n=181,174 | Maximum post BL, Protein, n=207,214 | |
| BUD/FOR 400/12 µg | -0.7 | 0.2 | -1.6 | 0.0 |
| FF/UMEC/VI 100/62.5/25 µg | -0.8 | 0.4 | -1.1 | 0.6 |
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12, Week 24 and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | International units per liter (IU/L) (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, ALT, n=181,173 | Maximum post BL, ALT, n=207,212 | Week 52, AST, n=180,174 | Maximum post BL, AST, n=207,214 | Week 52, ALP, n=181,174 | Maximum post BL, ALP, n=207,214 | Week 52, GGT, n=181,174 | Maximum post BL, GGT, n=207,214 | Week 52, Creatine Kinase, n=181,174 | Maximum post BL, Creatine Kinase, n=207,214 | |
| BUD/FOR 400/12 µg | 1.3 | 4.5 | 0.8 | 3.7 | -2.7 | 1.2 | 0.2 | 8.9 | 16.7 | 46.9 |
| FF/UMEC/VI 100/62.5/25 µg | 1.7 | 5.4 | 1.7 | 5.5 | 1.7 | 6.7 | 0.2 | 7.7 | 6.1 | 39.9 |
Hematology laboratory assessments included basophils, eosinophils, lymphocytes, monocytes, neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a repeat test). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | 10^9 cells/Liter(L) (Mean) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, Basophils, n=817,761 | Maximum post BL, Basophils, n=876,853 | Week 24, Eosinophils, n=817, 761 | Maxmium post BL, Eosinophils, n=876,853 | Category title 5. Week 24, Monocytes, n=817,761 | Maximum post BL, Monocytes, n=876,853 | Week 24, Neutrophils, n=817,761 | Maximum post BL, Neutrophils, n=876,853 | Week 24, Leukocytes, n=819,761 | Maximum post BL, Leukocytes, n=877,853 | Week 24, Platelets, n=810,759 | Maximum post BL, Platelets, n=871,846 | Week 24, Lymphocytes, n=817,761 | Maximum post BL, Lymphocytes, n=876,853 | |
| BUD/FOR 400/12 µg | -0.001 | 0.005 | -0.015 | 0.019 | 0.004 | 0.048 | 0.142 | 0.649 | 0.11 | 0.64 | -0.7 | 10.2 | -0.023 | 0.150 |
| FF/UMEC/VI 100/62.5/25 µg | -0.001 | 0.005 | -0.008 | 0.034 | -0.006 | 0.040 | 0.071 | 0.481 | 0.06 | 0.52 | -0.7 | 10.8 | 0.002 | 0.187 |
Hematology laboratory assessments included Basophils, eosinophils, lymphocytes, monocytes,neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | 10^9 cells/L (Mean) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, Basophils, n=168,166 | Maximum post BL, Basophils, n=205,212 | Week 52, Eosinophils, n=168,166 | Maximum post BL, Eosinophils, n=205,212 | Week 52, Monocytes, n=168,166 | Maximum post BL, Monocytes, n=205,212 | Week 52, Neutrophils, n=168,166 | Maximum post BL, Neutrophils, n=205,212 | Week 52, Leukocytes, n=168,166 | Maximum post BL, Leukocytes, n=205,212 | Week 52, Platelets, n=170,166 | Maximum post BL, Platelets, n=203,210 | Week 52, Lymphocytes, n=168,166 | Maximum post BL, Lymphocytes, n=202,212 | |
| BUD/FOR 400/12 µg | 0.003 | 0.010 | -0.011 | 0.057 | 0.028 | 0.072 | -0.163 | 0.835 | -0.17 | 0.87 | -2.7 | 13.9 | -0.027 | 0.295 |
| FF/UMEC/VI 100/62.5/25 µg | 0.002 | 0.011 | 0.002 | 0.074 | 0.025 | 0.075 | 0.246 | 0.923 | 0.33 | 0.97 | -1.8 | 13.6 | 0.060 | 0.325 |
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Micromoles per liter (Mean) | |||||
|---|---|---|---|---|---|---|
| Week 24, Bilirubin, n=839,786 | Maximum post BL, Bilirubin, n=888,865 | Week 24, Creatinine, n=839,787 | Maximum post BL, Creatinine, n=888,866 | Week 24, Urate, n=839,787 | Maximum post BL, Urate, n=888,866 | |
| BUD/FOR 400/12 µg | 0.1 | 1.2 | 1.14 | 3.99 | 1.7 | 21.9 |
| FF/UMEC/VI 100/62.5/25 µg | -0.2 | 1.1 | 1.05 | 4.12 | 2.8 | 23.7 |
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, Week 24, and Week 52 of the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Micromoles per liter (Mean) | |||||
|---|---|---|---|---|---|---|
| Week 52, Bilirubin, n=181,174 | Maximum post BL, Bilirubin, n=207,214 | Week 52, Creatinine, n=181,174 | Maximum post BL, Creatinine, n=207,214 | Week 52, Urate, n=181,174 | Maximum post BL, Urate, n=207,214 | |
| BUD/FOR 400/12 µg | 0.1 | 2.3 | 1.28 | 6.00 | 3.9 | 40.0 |
| FF/UMEC/VI 100/62.5/25 µg | 0.3 | 2.0 | 2.95 | 6.99 | 3.6 | 42.0 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Milliseconds (msec) (Least Squares Mean) | |
|---|---|---|
| QTcF, n=840,787 | PR, n=812,766 | |
| BUD/FOR 400/12 µg | 0.6 | 0.5 |
| FF/UMEC/VI 100/62.5/25 µg | 2.5 | -0.1 |
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | 10^12 cells/L (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | -0.04 | 0.04 |
| FF/UMEC/VI 100/62.5/25 µg | -0.02 | 0.06 |
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | 10^12 cells/L (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | 0.00 | 0.07 |
| FF/UMEC/VI 100/62.5/25 µg | 0.02 | 0.11 |
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, phophate, potassium, sodium, and urea at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Millimoles per liter (mmol/L) (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, Calcium, n=835,785 | Maximum post BL, Calcium, n=887,866 | Week 24, Chloride, n=838,787 | Maximum post BL, Chloride, n=888,866 | Week 24, CO2, n=835,785 | Maximum post BL, CO2, n=835,785 | Week 24, Glucose, n=839,787 | Maximum post BL, Glucose, n=887,866 | Week 24, Potassium, n=834,785 | Maximum post BL, Potassium, n=887,866 | Week 24, Phosphate, n=839,787 | Maximum post BL, Phosphate, n=888,866 | Week 24, Sodium, n=837,787 | Maximum post BL, Sodium, n=888,866 | Week 24, Urea, n=839,787 | Maximum post BL, Urea, n=888,866 | |
| BUD/FOR 400/12 µg | -0.014 | 0.012 | -0.7 | 0.6 | -0.0 | 0.5 | -0.00 | 0.37 | -0.03 | 0.13 | -0.029 | 0.043 | -0.2 | 0.7 | 0.04 | 0.64 |
| FF/UMEC/VI 100/62.5/25 µg | -0.016 | 0.013 | -0.4 | 0.9 | -0.6 | 0.0 | 0.12 | 0.53 | 0.04 | 0.18 | -0.028 | 0.039 | -0.3 | 0.6 | 0.08 | 0.68 |
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, magnesium, phophate, potassium, sodium, and urea at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Mmol/L (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, Calcium, n=180,174 | Maximum post BL,Calcium, n=207,214 | Week 52, Chloride, n=181,174 | Maximum post BL,Chloride, n=207,214 | Week 52, CO2, n=180,174 | Maximum post BL,CO2, n=207,214 | Week 52, Glucose, n=181,174 | Maximum post BL,Glucose, n=207,214 | Week 52, Potassium, n=180,174 | Maximum post BL,Potassium, n=207,214 | Week 52, Phosphate, n=181,174 | Maximum post BL,Phosphate, n=207,214 | Week 52, Sodium, n=181,174 | Maximum post BL,Sodium, n=207,214 | Week 52, Urea, n=181,174 | Maximum post BL, Urea, n=207,214 | |
| BUD/FOR 400/12 µg | -0.040 | 0.008 | -0.2 | 1.3 | -1.0 | 0.3 | 0.22 | 0.63 | -0.10 | 0.20 | 0.005 | 0.110 | -0.1 | 1.1 | 0.12 | 1.08 |
| FF/UMEC/VI 100/62.5/25 µg | -0.033 | 0.026 | -0.1 | 1.4 | -1.2 | -0.2 | 0.31 | 0.92 | -0.02 | 0.29 | -0.003 | 0.109 | -0.2 | 1.1 | 0.16 | 1.06 |
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Fraction of 1 (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | 0.0024 | 0.0123 |
| FF/UMEC/VI 100/62.5/25 µg | 0.0024 | 0.0115 |
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as Most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Fraction of 1 (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | -0.0056 | 0.0149 |
| FF/UMEC/VI 100/62.5/25 µg | -0.0056 | 0.0153 |
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Grams per liter (g/L) (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | -1.0 | 1.5 |
| FF/UMEC/VI 100/62.5/25 µg | -0.9 | 1.5 |
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | g/L (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | -2.5 | 1.9 |
| FF/UMEC/VI 100/62.5/25 µg | -2.5 | 2.2 |
Single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Msec (Least Squares Mean) | |
|---|---|---|
| QTcF, n=181,169 | PR, n=174,160 | |
| BUD/FOR 400/12 µg | 2.4 | 1.4 |
| FF/UMEC/VI 100/62.5/25 µg | 1.4 | 1.6 |
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were collected taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Millimeter of mercury (mmHg) (Least Squares Mean) | |
|---|---|---|
| SBP | DBP | |
| BUD/FOR 400/12 µg | -1.1 | -0.5 |
| FF/UMEC/VI 100/62.5/25 µg | -1.0 | -0.3 |
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 52 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | mmHg (Least Squares Mean) | |
|---|---|---|
| SBP | DBP | |
| BUD/FOR 400/12 µg | 0.3 | 0.4 |
| FF/UMEC/VI 100/62.5/25 µg | -1.3 | -0.4 |
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, Candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Oral candidiasis | Candida infection | Oral fungal infection | Oropharyngeal candidiasis | |
| BUD/FOR 400/12 µg | 4 | 4 | 3 | 0 |
| FF/UMEC/VI 100/62.5/25 µg | 2 | 1 | 2 | 2 |
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Candida infection | Oral fungal infection | |
| BUD/FOR 400/12 µg | 3 | 2 |
| FF/UMEC/VI 100/62.5/25 µg | 0 | 0 |
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |
|---|---|---|
| Any AE | Any SAE | |
| BUD/FOR 400/12 µg | 339 | 51 |
| FF/UMEC/VI 100/62.5/25 µg | 354 | 49 |
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Any AE | Any SAE | |
| BUD/FOR 400/12 µg | 122 | 28 |
| FF/UMEC/VI 100/62.5/25 µg | 100 | 21 |
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query [SMQ; myocardial infarction SMQ and other ischemic diseases]) and narrow MACE criteria (myocardial infarction [acute myocardial infarction]. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |
|---|---|---|
| Any MACE, Narrow definition | Any MACE, Broad definition | |
| BUD/FOR 400/12 µg | 7 | 11 |
| FF/UMEC/VI 100/62.5/25 µg | 4 | 12 |
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query [SMQ; myocardial infarction SMQ and other ischemic diseases]) and narrow MACE criteria (myocardial infarction [acute myocardial infarction] (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Any MACE, Narrow definition | Any MACE, Broad definition | |
| BUD/FOR 400/12 µg | 2 | 5 |
| FF/UMEC/VI 100/62.5/25 µg | 5 | 7 |
A single 12-lead electrocardiogram (ECG) and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Beats per minute (Bpm) (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -1.1 |
| BUD/FOR 400/12 µg | -1.2 |
Participants were asked to complete the daily activity question as aprt of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.0 |
| BUD/FOR 400/12 µg | 0.3 |
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, >=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Exacerbations per participant per year (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.22 |
| BUD/FOR 400/12 µg | 0.34 |
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, >=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Exacerbations per participant per year (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.20 |
| BUD/FOR 400/12 µg | 0.36 |
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray AND at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature > 37.5 °C), Elevated WBC (>10,000/mm3 or >15 percent immature forms) orr Hypoxemia (HbO2 saturation <88 percent or at least 2 percent lower than Baseline value). (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 4 |
| BUD/FOR 400/12 µg | 4 |
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray and at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature > 37.5 °C), Elevated white blood cells (WBC) (>10,000/millimeter [mm^3] or >15 percent immature forms) or Hypoxemia (hemoglobin/oxygen [HbO2] saturation <88 percent or at least 2 percent lower than Baseline value). (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 20 |
| BUD/FOR 400/12 µg | 7 |
The 24-hour holter measurements were obtained at Screening and 24 hours prior to Week 24 (Visits 1 and 6). The number of participants with clinically significant change (abnormal) were reported. Holter Monitoring Population: all participants in the ITT Population who had at least one holter monitoring evaluation. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| Overall Study Arm | 180 |
| BUD/FOR 400/12 µg | 165 |
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0 |
| BUD/FOR 400/12 µg | 1 |
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 4 |
| BUD/FOR 400/12 µg | 6 |
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Week 4 and Week 24. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions. (NCT02345161)
Timeframe: Week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 2.29 |
| BUD/FOR 400/12 µg | 1.72 |
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Weeks 4, 24 and 52. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions (NCT02345161)
Timeframe: Week 52
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 1.74 |
| BUD/FOR 400/12 µg | 1.39 |
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 1-4, n=870,859 | Week 5-8, n=851,830 | Week 9-12, n=841,813 | Week 13-16, n=831,802 | Week 17-20, n=828,788 | Week 21-24, n=825,783 | Breathlessness score, Week 1-4, n=870,859 | Breathlessness score, Week 5-8, n=851,830 | Breathlessness score, Week 9-12, n=841,813 | Breathlessness score, Week 13-16, n=831, 802 | Breathlessness score, Week 17-20, n=828,788 | Breathlessness score, Week 21-24, n=825,783 | Cough, sputum score, Week 1-4, n=870,859 | Cough, sputum score, Week 5-8, n=851,830 | Cough, sputum score, Week 9-12, n=841,813 | Cough, sputum score, Week 13-16, n=831,802 | Cough, sputum score, Week 17-20, n=828,788 | Cough, sputum score, Week 21-24, n=825,783 | Chest score, Week 1-4, n=870,859 | Chest score, Week 5-8, n=851,830 | Chest score, Week 9-12, n=841,813 | Chest score, Week 13-16, n=831,802 | Chest score, Week 17-20, n=828,788 | Chest score, Week 21-24, n=825,783 | |
| BUD/FOR 400/12 µg | -0.50 | -0.77 | -1.05 | -1.09 | -1.02 | -0.96 | -0.20 | -0.26 | -0.34 | -0.36 | -0.31 | -0.30 | -0.24 | -0.39 | -0.50 | -0.53 | -0.53 | -0.50 | -0.06 | -0.12 | -0.20 | -0.20 | -0.17 | -0.17 |
| FF/UMEC/VI 100/62.5/25 µg | -1.45 | -2.00 | -2.23 | -2.42 | -2.43 | -2.31 | -0.71 | -0.95 | -1.03 | -1.11 | -1.10 | -1.07 | -0.41 | -0.59 | -0.67 | -0.74 | -0.77 | -0.72 | -0.33 | -0.46 | -0.54 | -0.58 | -0.57 | -0.53 |
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 1-4, n=205, 213 | Week 5-8, n=203, 208 | Week 9-12, n=201, 206 | Week 13-16, n=201, 204 | Week 17-20, n=201, 199 | Week 21-24, n=202, 197 | Week 25-28, n=194, 186 | Week 29-32, n=192, 181 | Week 33-36, n=187, 180 | Week 37-40, n=185, 177 | Week 41-44, n=180, 174 | Week 45-48, n=180, 173 | EXACT-RS Scores, Week 49-52, n=179, 171 | Breathlessness scores, Week 1-4, n=205, 213 | Breathlessness scores, Week 5-8, n=203, 208 | Breathlessness scores, Week 9-12, n=201, 206 | Breathlessness scores, Week 13-16, n=201, 204 | Breathlessness scores, Week 17-20, n=201, 199 | Breathlessness scores, Week 21-24, n=202, 197 | Breathlessness scores, Week 25-28, n=194, 186 | Breathlessness scores, Week 29-32, n=192, 181 | Breathlessness scores, Week 33-36, n=187, 180 | Breathlessness scores, Week 37-40, n=185, 177 | Breathlessness scores, Week 41-44, n=180, 174 | Breathlessness scores, Week 45-48, n=180, 173 | Breathlessness scores, Week 49-52, n=179, 171 | Cough and sputum scores, Week 1-4, n=205, 213 | Cough and sputum scores, Week 5-8, n=203, 208 | Cough and sputum scores, Week 9-12, n=201, 206 | Cough and sputum scores, Week 13-16, n=201, 204 | Cough and sputum scores, Week 17-20, n=201, 199 | Cough and sputum scores, Week 21-24, n=202, 197 | Cough and sputum scores, Week 25-28, n=194, 186 | Cough and sputum scores, Week 29-32, n=192, 181 | Cough and sputum scores, Week 33-36, n=187, 180 | Cough and sputum scores, Week 37-40, n=185, 177 | Cough and sputum scores, Week 41-44, n=180, 174 | Cough and sputum scores, Week 45-48, n=180, 173 | Cough and sputum scores, Week 49-52, n=179, 171 | Chest scores, Week 1-4, n=205, 213 | Chest scores, Week 5-8, n=203, 208 | Chest scores, Week 9-12, n=201, 206 | Chest scores, Week 13-16, n=201, 204 | Chest scores, Week 17-20, n=201, 199 | Chest scores, Week 21-24, n=202, 197 | Chest scores, Week 25-28, n=194, 186 | Chest scores, Week 29-32, n=192, 181 | Chest scores, Week 33-36, n=187, 180 | Chest scores, Week 37-40, n=185, 177 | Chest scores, Week 41-44, n=180, 174 | Chest scores, Week 45-48, n=180, 173 | Chest scores, Week 49-52, n=179, 171 | |
| BUD/FOR 400/12 µg | -0.72 | -0.90 | -1.21 | -1.52 | -1.53 | -1.52 | -1.16 | -0.90 | -0.62 | -1.11 | -0.81 | -0.64 | -0.61 | -0.31 | -0.32 | -0.44 | -0.57 | -0.50 | -0.50 | -0.38 | -0.26 | -0.14 | -0.37 | -0.24 | -0.11 | -0.08 | -0.32 | -0.44 | -0.52 | -0.62 | -0.73 | -0.71 | -0.57 | -0.48 | -0.40 | -0.54 | -0.41 | -0.39 | -0.44 | -0.09 | -0.13 | -0.24 | -0.31 | -0.29 | -0.30 | -0.21 | -0.16 | -0.08 | -0.20 | -0.16 | -0.13 | -0.08 |
| FF/UMEC/VI 100/62.5/25 µg | -1.24 | -1.97 | -2.18 | -2.53 | -2.64 | -2.63 | -2.48 | -2.33 | -2.12 | -2.34 | -2.30 | -2.17 | -2.03 | -0.64 | -0.93 | -1.05 | -1.19 | -1.17 | -1.13 | -1.14 | -1.11 | -1.08 | -1.13 | -1.06 | -0.97 | -0.96 | -0.34 | -0.59 | -0.63 | -0.73 | -0.83 | -0.83 | -0.73 | -0.68 | -0.56 | -0.65 | -0.66 | -0.66 | -0.61 | -0.27 | -0.46 | -0.51 | -0.61 | -0.67 | -0.68 | -0.63 | -0.55 | -0.48 | -0.57 | -0.58 | -0.57 | -0.49 |
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12 and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | International units per liter (IU/L) (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, ALT, n=838,785 | Maximum post BL, ALT, n=887,864 | Week 24, AST, n=835,785 | Maximum post BL, AST, n=887,866 | Week 24, ALP, n=839,787 | Maximum post BL, ALP, n=888,866 | Week 24, GGT, n=839,787 | Maximum post BL, GGT, n=888,866 | Week 24, Creatine Kinase, n=839,787 | Maximum post BL, Creatine Kinase, n=888,866 | |
| BUD/FOR 400/12 µg | 3.8 | 5.5 | 4.0 | 5.6 | -2.8 | 0.8 | 0.5 | 4.7 | -3.4 | 20.6 |
| FF/UMEC/VI 100/62.5/25 µg | 1.4 | 3.0 | 1.1 | 3.2 | 1.1 | 4.3 | 3.4 | 7.5 | -3.9 | 20.6 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Bpm (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.2 |
| BUD/FOR 400/12 µg | -1.0 |
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Bpm (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -0.5 |
| BUD/FOR 400/12 µg | -0.8 |
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 52 were summarized and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Bpm (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.7 |
| BUD/FOR 400/12 µg | -1.9 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Msec (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 1.5 |
| BUD/FOR 400/12 µg | -0.7 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24, and Week 52 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 52. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Msec (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.9 |
| BUD/FOR 400/12 µg | 2.2 |
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 24 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -6.6 |
| BUD/FOR 400/12 µg | -4.3 |
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 52 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -4.6 |
| BUD/FOR 400/12 µg | -1.9 |
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. ITT Population comprised of all randomized subjects excluding those who were randomized in error. Only participants with analyzable data at the given time point were analyzed. (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Liters (L) (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.142 |
| BUD/FOR 400/12 µg | -0.029 |
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 52 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. Extension Population: all participants in the ITT Population who were enrolled into the subset of participants with extension to 52 weeks. (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Liters (L) (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.126 |
| BUD/FOR 400/12 µg | -0.053 |
Participants were asked to complete the daily activity question as part of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| FF/UMEC/VI (100 mcg/62.5 mcg/25 mcg) | 0.0 |
| Budesonide/Formoterol (400 mcg/12 mcg) | -0.1 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit [up to Day 50]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT02495168)
Timeframe: Day 1 up to Day 50
| Intervention | liters (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 0.278 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 0.283 |
| Placebo | 0.094 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit [up to Day 50]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT02495168)
Timeframe: Day 1 up to Day 50
| Intervention | liters (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 0.269 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 0.277 |
| Placebo | 0.124 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis. (NCT02495168)
Timeframe: 0 to 12 hours on Day 1
| Intervention | Liter*hour (Lh) (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 3.637 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 3.584 |
| Placebo | 1.460 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis. (NCT02495168)
Timeframe: 0 to 12 hours on Day 1
| Intervention | Lh (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 3.630 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 3.573 |
| Placebo | 1.449 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.276 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.278 |
| BFF MDI (PT009) 320/9.6 μg | 0.234 |
| Symbicort® | 0.247 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.181 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.194 |
| BFF MDI (PT009) 320/9.6 μg | 0.167 |
| Symbicort® | 0.163 |
Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand (NCT02497001)
Timeframe: at Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.124 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.111 |
| BFF MDI (PT009) 320/9.6 μg | 0.050 |
| Symbicort® | 0.062 |
Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand (NCT02497001)
Timeframe: over 24 Weeks
| Intervention | Puffs (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | -1.3 |
| GFF MDI (PT003) 14.4/9.6 μg | -1.1 |
| BFF MDI (PT009) 320/9.6 μg | -1.1 |
| Symbicort® | -1.6 |
Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand (NCT02497001)
Timeframe: over 24 Weeks
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.147 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.125 |
| BFF MDI (PT009) 320/9.6 μg | 0.073 |
| Symbicort® | 0.088 |
Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand (NCT02497001)
Timeframe: at Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.370 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.361 |
| BFF MDI (PT009) 320/9.6 μg | 0.253 |
| Symbicort® | 0.264 |
FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)). (NCT02497001)
Timeframe: at Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.292 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.288 |
| BFF MDI (PT009) 320/9.6 μg | 0.177 |
| Symbicort® | 0.189 |
Change from BGF (NCT02497001)
Timeframe: at Week 24
| Intervention | Percentage (Least Squares Mean) |
|---|---|
| GFF MDI (PT003) 14.4/9.6 μg | 6.06 |
| BFF MDI (PT009) 320/9.6 μg | 6.43 |
| Symbicort® | 8.23 |
Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand (NCT02497001)
Timeframe: over 24 weeks
| Intervention | Exacerbations (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.46 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.95 |
| BFF MDI (PT009) 320/9.6 μg | 0.56 |
| Symbicort® | 0.55 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.268 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.282 |
| BFF MDI (PT009) 320/9.6 μg | 0.228 |
| Symbicort® | 0.232 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.217 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.230 |
| BFF MDI (PT009) 320/9.6 μg | 0.197 |
| Symbicort® | 0.190 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.281 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.292 |
| BFF MDI (PT009) 320/9.6 μg | 0.241 |
| Symbicort® | 0.244 |
FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand (NCT02497001)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| BGF MDI 320/14.4/9.6 μg | 0.236 |
| GFF MDI (PT003) 14.4/9.6 μg | 0.255 |
| BFF MDI (PT009) 320/9.6 μg | 0.213 |
| Symbicort® | 0.208 |
Device preference for either Spiromax or Turbohaler device at baseline assessed by PASAPQ Part II Q15 score (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | percent of participants (Number) |
|---|---|
| Budesonide/Formoterol (BF) Spiromax® | 74 |
| SYMBICORT Turbohaler® | 16 |
| No Preference | 10 |
Number of participants achieving mastery at each level in the 6 level training process at baseline visit as assessed by expert assessor (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| Level 1: Intuitive Use | Level 2: Patient Information Leaflet | Level 3: Instructional Video | Level 4: Expert Tuition | Level 5: Repeat of Expert Tuition | Level 6: Second Repeat of Expert Tuition | |
| Budesonide/Formoterol (BF) Spiromax® | 113 | 186 | 87 | 116 | 13 | 1 |
| SYMBICORT Turbohaler® | 20 | 142 | 176 | 158 | 19 | 1 |
Number of participants achieving mastery at each level in the 6 level training process after 8 weeks from baseline visit as assessed by expert assessor (NCT02570425)
Timeframe: 8 weeks
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| Level 1: Intuitive Use | Level 2: Patient Information Leaflet | Level 3: Instructional Video | Level 4: Expert Tuition | Level 5: Repeat of Expert Tuition | Level 6: Second Repeat of Expert Tuition | |
| Budesonide/Formoterol (BF) Spiromax® | 362 | 63 | 20 | 19 | 0 | 0 |
| SYMBICORT Turbohaler® | 299 | 127 | 16 | 14 | 0 | 0 |
Number of levels required to achieve device mastery out of a 6 level training processrequired by each patient at each visit as assessed by expert assessor (NCT02570425)
Timeframe: 4 weeks
| Intervention | levels (Mean) | ||
|---|---|---|---|
| Visit 1 | Visit 2 | Visit 3 | |
| Budesonide/Formoterol (BF) Spiromax® | 2.48 | 1.57 | 1.33 |
| SYMBICORT Turbohaler® | 3.03 | 1.94 | 1.45 |
(NCT02570425)
Timeframe: 4 weeks
| Intervention | errors (Number) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Not holding device with mouthpiece cover at bottom | Device is not held upright (±90°) during dose prep | Device is not held upright (±45°) during dose prep | Not twisting the base until it clicks | Vigorous shaking before or after dose preparation | Exhales into the device before taking a dose | Inhalation is not as fast as possible from start | Does not remove cap | Inhaler not held upright (± 45°) until inhalation | Fails to seal lips around mouthpi | Puts fingers or mouth/face around air inlets | Does not open cap | A click is not heard when the cap is opened | |
| Budesonide/Formoterol (BF) Spiromax® | 6 | 106 | 0 | 0 | 19 | 23 | 148 | 0 | 0 | 15 | 0 | 0 | 2 |
| SYMBICORT Turbohaler® | 0 | 0 | 184 | 204 | 8 | 36 | 166 | 0 | 119 | 20 | 43 | 0 | 0 |
(NCT02570425)
Timeframe: 8 weeks
| Intervention | errors (Number) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Not holding device with mouthpiece cover at bottom | Device is not held upright (±90°) during dose prep | Device is not held upright (±45°) during dose prep | Not twisting the base until it clicks | Vigorous shaking before or after dose preparation | Exhales into the device before taking a dose | Inhalation is not as fast as possible from start | Does not remove cap | Inhaler not held upright (± 45°) until inhalation | Fails to seal lips around mouthpi | Puts fingers or mouth/face around air inlets | Does not open cap | A click is not heard when the cap is opened | |
| Budesonide/Formoterol (BF) Spiromax® | 3 | 34 | 0 | 0 | 6 | 12 | 71 | 0 | 0 | 5 | 41 | 0 | 0 |
| SYMBICORT Turbohaler® | 0 | 0 | 70 | 49 | 2 | 19 | 82 | 0 | 30 | 5 | 39 | 0 | 0 |
(NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | errors (Number) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Not holding device with mouthpiece cover at bottom | Device is not held upright (±90°) during dose prep | Device is not held upright (±45°) during dose prep | Not twisting the base until it clicks | Vigorous shaking before or after dose preparation | Exhales into the device before taking a dose | Inhalation is not as fast as possible from start | Does not remove cap | Inhaler not held upright (± 45°) until inhalation | Fails to seal lips around mouthpi | Puts fingers or mouth/face around air inlets | Does not open cap | A click is not heard when the cap is opened | |
| Budesonide/Formoterol (BF) Spiromax® | 62 | 318 | 0 | 0 | 78 | 61 | 613 | 0 | 0 | 131 | 105 | 28 | 51 |
| SYMBICORT Turbohaler® | 0 | 0 | 614 | 557 | 29 | 101 | 581 | 6 | 402 | 157 | 93 | 0 | 0 |
Number of participants achieving mastery at each level in the 6 level training process after 4 weeks from baseline visit as assessed by expert assessor (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| Level 1: Intuitive Use | Level 2: Patient Information Leaflet | Level 3: Instructional Video | Level 4: Expert Tuition | Level 5: Repeat of Expert Tuition | Level 6: Second Repeat of Expert Tuition | |
| Budesonide/Formoterol (BF) Spiromax® | 317 | 113 | 34 | 31 | 3 | 0 |
| SYMBICORT Turbohaler® | 202 | 182 | 60 | 47 | 7 | 0 |
Quantity of errors made at each level recalled by expert assessors at 8 weeks after baseline visit by all participants (NCT02570425)
Timeframe: 8 weeks
| Intervention | errors (Number) |
|---|---|
| SYMBICORT Turbohaler® | 296 |
| Budesonide/Formoterol (BF) Spiromax® | 175 |
Quantity of errors made at each level recalled by expert assessors at 4 weeks after baseline visit by all participants (NCT02570425)
Timeframe: 4 weeks
| Intervention | errors (Number) |
|---|---|
| SYMBICORT Turbohaler® | 780 |
| Budesonide/Formoterol (BF) Spiromax® | 367 |
Quantity of errors made at each level recalled during baseline visit by all participants using an expert assessor (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | errors (Number) |
|---|---|
| SYMBICORT Turbohaler® | 2540 |
| Budesonide/Formoterol (BF) Spiromax® | 1447 |
Examined for both at the end of level 1 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 4 |
| Budesonide/Formoterol (BF) Spiromax® | 22 |
Examined at the end of level 1 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 4 weeks
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 40 |
| Budesonide/Formoterol (BF) Spiromax® | 64 |
Examined for both at the end of level 1 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 8 weeks
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 65 |
| Budesonide/Formoterol (BF) Spiromax® | 79 |
Examined for both at the end of level 2 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 0 weeks (Visit 1)
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 31 |
| Budesonide/Formoterol (BF) Spiromax® | 58 |
Examined at the end of level 2 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 4 weeks
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 77 |
| Budesonide/Formoterol (BF) Spiromax® | 86 |
Examined for both at the end of level 2 (out of 6 level training process). This will be compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate. (NCT02570425)
Timeframe: 8 weeks
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 93 |
| Budesonide/Formoterol (BF) Spiromax® | 92 |
"Examine if recall of device mastery is superior for the SPIROMAX inhaler as compared to the TURBOHALER after training to device mastery on both devices.~The proportion of subjects achieving mastery of inhaler technique between the two inhaler devices was compared using McNemar's test of equality of paired proportions with a 0.050 two- sided significance level. A Conditional Logistic Regression Model was used to quantify the difference between the two inhalers by calculating the odds ratio for achieving mastery for Spiromax® (with Turbohaler® as the reference device) along with a 95% confidence interval for quantifying the precision of the odds ratio estimate." (NCT02570425)
Timeframe: 4 weeks
| Intervention | percent of participants (Number) |
|---|---|
| SYMBICORT Turbohaler® | 40 |
| Budesonide/Formoterol (BF) Spiromax® | 64 |
Device preference for either Spiromax or Turbohaler device 4 weeks after baseline visit assessed by PASAPQ Part II Q15 score (NCT02570425)
Timeframe: 4 weeks
| Intervention | percent of participants (Number) |
|---|---|
| Budesonide/Formoterol (BF) Spiromax® | 74.5 |
| SYMBICORT Turbohaler® | 15.5 |
| No Preference | 10 |
Device preference for either Spiromax or Turbohaler device 8 weeks after baseline visit assessed by PASAPQ Part II Q15 score (NCT02570425)
Timeframe: 8 weeks
| Intervention | percent of participants (Number) |
|---|---|
| Budesonide/Formoterol (BF) Spiromax® | 79 |
| SYMBICORT Turbohaler® | 14 |
| No Preference | 7 |
Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 3.37 |
| Treatment B | 3.88 |
| Treatment C | 3.36 |
| Treatment D | 3.76 |
Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 10.1 |
| Treatment B | 11.9 |
| Treatment C | 10.3 |
| Treatment D | 11.7 |
Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 3.21 |
| Treatment B | 3.14 |
| Treatment C | 3.23 |
| Treatment D | 3.01 |
Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 9.35 |
| Treatment B | 9.28 |
| Treatment C | 9.45 |
| Treatment D | 9.08 |
Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 313 |
| Treatment B | 238 |
| Treatment C | 315 |
| Treatment D | 237 |
Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.080 |
| Treatment B | 0.080 |
| Treatment C | 0.080 |
| Treatment D | 0.080 |
Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1820 |
| Treatment B | 1830 |
| Treatment C | 1670 |
| Treatment D | 1640 |
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1710 |
| Treatment B | 1710 |
| Treatment C | 1570 |
| Treatment D | 1530 |
PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | L/min (Mean) |
|---|---|
| Treatment A | 32.3 |
| Treatment B | 22.4 |
| Treatment C | 30.3 |
| Treatment D | 19.3 |
Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.080 |
| Treatment B | 0.250 |
| Treatment C | 0.040 |
| Treatment D | 0.250 |
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 46.1 |
| Treatment B | 52.6 |
| Treatment C | 39.0 |
| Treatment D | 42.8 |
FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | liters (Mean) |
|---|---|
| Treatment A | 0.188 |
| Treatment B | 0.170 |
| Treatment C | 0.173 |
| Treatment D | 0.153 |
Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 55.4 |
| Treatment B | 63.0 |
| Treatment C | 46.8 |
| Treatment D | 53.7 |
"FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath.~FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | Ratio (Mean) |
|---|---|
| Treatment A | 3.94 |
| Treatment B | 3.78 |
| Treatment C | 3.75 |
| Treatment D | 3.83 |
Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 1080 |
| Treatment B | 686 |
| Treatment C | 1110 |
| Treatment D | 663 |
The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI, FF MDI, BD MDI, & Symbicort TBH on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. (NCT02766608)
Timeframe: at Week 24
| Intervention | Percentage of Subjects (Number) |
|---|---|
| BFF MDI 320/9.6 μg | 48.12 |
| BFF MDI 160/9.6 μg | 47.22 |
| FF MDI 9.6 μg | 41.59 |
| BD MDI 320 μg | 43.62 |
| Symbicort TBH 400/12 μg | 53.78 |
Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.272 |
| BFF MDI 160/9.6 μg | 0.258 |
| FF MDI 9.6 μg | 0.243 |
| BD MDI 320 μg | 0.116 |
| Symbicort TBH 400/12 μg | 0.267 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 5 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.157 |
| BFF MDI 160/9.6 μg | 0.151 |
| FF MDI 9.6 μg | 0.160 |
| BD MDI 320 μg | 0.025 |
| Symbicort TBH 400/12 μg | 0.131 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 4 Hours
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.230 |
| BFF MDI 160/9.6 μg | 0.215 |
| FF MDI 9.6 μg | 0.212 |
| BD MDI 320 μg | 0.073 |
| Symbicort TBH 400/12 μg | 0.209 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 30 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.207 |
| BFF MDI 160/9.6 μg | 0.207 |
| FF MDI 9.6 μg | 0.215 |
| BD MDI 320 μg | 0.047 |
| Symbicort TBH 400/12 μg | 0.190 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 2 Hours
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.253 |
| BFF MDI 160/9.6 μg | 0.234 |
| FF MDI 9.6 μg | 0.244 |
| BD MDI 320 μg | 0.063 |
| Symbicort TBH 400/12 μg | 0.221 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 15 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.190 |
| BFF MDI 160/9.6 μg | 0.186 |
| FF MDI 9.6 μg | 0.201 |
| BD MDI 320 μg | 0.040 |
| Symbicort TBH 400/12 μg | 0.167 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 1 Hour
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.225 |
| BFF MDI 160/9.6 μg | 0.221 |
| FF MDI 9.6 μg | 0.236 |
| BD MDI 320 μg | 0.053 |
| Symbicort TBH 400/12 μg | 0.211 |
Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.036 |
| BFF MDI 160/9.6 μg | 0.017 |
| FF MDI 9.6 μg | -0.003 |
| BD MDI 320 μg | -0.028 |
| Symbicort TBH 400/12 μg | 0.039 |
Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.036 |
| BFF MDI 160/9.6 μg | 0.017 |
| FF MDI 9.6 μg | -0.003 |
Changes from baseline in FEV1 AUC0-4 were normalized by taking the area under the curve value and dividing by the length of time under consideration (usually 4 hours). This normalization represents a weighted average of the change from baseline in FEV1 over the 4-hour period. (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.194 |
| BFF MDI 160/9.6 μg | 0.179 |
| FF MDI 9.6 ug | 0.161 |
| BD MDI 320 ug | 0.022 |
| Symbicort TBH 400/12 ug | 0.187 |
Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: over 24 Weeks
| Intervention | Puffs per day (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | -1.3 |
| BFF MDI 160/9.6 μg | -1.3 |
| FF MDI 9.6 μg | -1.1 |
| BD MDI 320 μg | -0.6 |
| Symbicort TBH 400/12 μg | -1.2 |
Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI). (NCT02766608)
Timeframe: over 24 Weeks (timepoints of 4, 12 & 20 weeks)
| Intervention | Percentage of Participants (Number) | ||
|---|---|---|---|
| Percentage of Subjects to Exacerbate at 4 Weeks | Percentage of Subjects to Exacerbate at 12 Weeks | Percentage of Subjects to Exacerbate at 20 Weeks | |
| BD MDI 320 μg | 7.0 | 14.9 | 17.7 |
| BFF MDI 160/9.6 μg | 3.3 | 9.9 | 18.5 |
| BFF MDI 320/9.6 μg | 3.2 | 9.8 | 14.4 |
| FF MDI 9.6 μg | 5.5 | 15.0 | 20.5 |
| Symbicort TBH 400/12 ug | 1.8 | 8.6 | 13.1 |
Substudy: 12-hour PFT (Pulmonary Function Test) endpoint FEV1 (Forced Expiratory Volume) AUC0-12 (Area under the Curve 0-12). Changes from baseline in FEV1 AUC0-12 were normalized by taking the area under the curve value and dividing by the length of time under consideration. This normalization represents a weighted average of the change from baseline in FEV1 over the 12-hour period. (NCT02766608)
Timeframe: at Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.135 |
| BFF MDI 160/9.6 μg | 0.124 |
| FF MDI 9.6 μg | 0.117 |
| BD MDI 320 μg | 0.024 |
Number of participants reporting at least one adverse event (safety population) (NCT03015259)
Timeframe: 6 Weeks
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Upper respiratory tract infection | Nasopharyngitis | Viral upper respiratory tract infection | Bronchitis | Asthma | Cough | Headache | Chest discomfort | |
| Treatment 1 | 12 | 7 | 6 | 3 | 17 | 4 | 4 | 1 |
| Treatment 2 | 15 | 11 | 4 | 4 | 24 | 4 | 8 | 0 |
| Treatment 3 | 7 | 4 | 1 | 2 | 39 | 3 | 2 | 2 |
Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42 (+/- 7 days). Baseline was defined as the average of 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT03015259)
Timeframe: Day 1 - Day 49
| Intervention | liter (Least Squares Mean) |
|---|---|
| Treatment 1 | 0.3096 |
| Treatment 2 | 0.3077 |
| Treatment 3 | 0.1236 |
FEV1 Area calculated over 12 hours (measurements at 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose) on Day 1 of treatment. Because this was a primary endpoint, Per Protocol Population used to calculate this endpoint. (NCT03015259)
Timeframe: Day 1
| Intervention | l * hr (Least Squares Mean) |
|---|---|
| Treatment 1 | 4.4453 |
| Treatment 2 | 4.2790 |
| Treatment 3 | 1.6876 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and reporting and analysis plan (RAP)." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 25 |
| Relvar Ellipta | 10 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 0 |
| Relvar Ellipta+LAMA | 8 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 4 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 11 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 13 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 0 |
| Symbicort Turbuhaler | 8 |
| Seretide Diskus | 11 |
| Spiriva Handihaler | 21 |
| Incruse/Anoro Ellipta | 0 |
| Ultibro/Seebri Breezhaler | 17 |
| Relvar Ellipta+LAMA | 6 |
| Symbicort Turbuhaler+LAMA | 6 |
| Seretide Diskus+LAMA | 13 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants with at least one overall error in primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 57 |
| Relvar Ellipta | 34 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. Errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. Percentage of participants making at least one overall error in either one or both devices (where applicable) is presented.The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 40 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 72 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 74 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants with at least one overall error in primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 34 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 67 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 63 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. Errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. Percentage of participants making at least one overall error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 34 |
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 71 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 16 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 47 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 36 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 11 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 39 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 26 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 10 |
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 41 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 10 |
| Relvar Ellipta+LAMA | 22 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants making at least one overall error in the primary DPI is presented." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 12 |
| Symbicort Turbuhaler | 35 |
| Seretide Diskus | 27 |
| Spiriva Handihaler | 36 |
| Incruse/Anoro Ellipta | 8 |
| Ultibro/Seebri Breezhaler | 32 |
| Relvar Ellipta+LAMA | 14 |
| Symbicort Turbuhaler+LAMA | 14 |
| Seretide Diskus+LAMA | 28 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 14 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 33 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 34 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants making at least one overall error in either one or both devices (where applicable) is presented." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 12 |
| Relvar Ellipta+LAMA | 16 |
Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on correct use of inhalers. Any error made by the participant was recorded by HCP in the checklist. Checklist of instructions for correct use were based on steps for correct use listed in PILs for the respective DPI. Errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per PIL. Overall errors is the combination of critical and non-critical errors. Percentage of participants making at least one overall error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP. (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 12 |
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 29 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps listed in PILs for the respective DPI. The errors were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants making at least one overall error in primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP.~." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 13 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 25 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 27 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps listed in PILs for the respective DPI. The errors were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants making at least one overall error in primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one overall error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 19 |
| Relvar Ellipta | 12 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants with at least one overall error in the primary DPI is presented." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 34 |
| Symbicort Turbuhaler | 64 |
| Seretide Diskus | 60 |
| Spiriva Handihaler | 74 |
| Incruse/Anoro Ellipta | 37 |
| Ultibro/Seebri Breezhaler | 55 |
| Relvar Ellipta+LAMA | 34 |
| Symbicort Turbuhaler+LAMA | 70 |
| Seretide Diskus+LAMA | 66 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in either one or both devices (where applicable) is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 0 |
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 13 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta and Ellipta+LAMA versus Turbuhaler and Turbuhaler+LAMA and Diskus and Diskus+LAMA; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta+[Relvar Ellipta+LAMA] | 3 |
| Symbicort Turbuhaler+[Symbicort Turbuhaler+LAMA] | 7 |
| Seretide Diskus+[Seretide Diskus+LAMA] | 12 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 2 within 6 weeks after they were retrained on the correct use of inhalers. Any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented. The aim of the analysis was to compare percentage of participants making at least one critical error with Ellipta versus all ICS/LABA+LAMA DPIs; hence, the arms were combined as pre-specified in the protocol and RAP." (NCT03114969)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|---|
| [Relvar Ellipta+LAMA]+[Symb Turb+LAMA]+[Seretide Diskus+LAMA] | 8 |
| Relvar Ellipta | 0 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the health care practitioner (HCP) in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in patient instruction leaflets (PILs) for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose. The percentage of participants making at least one critical error in the primary DPI is presented. The analysis was performed on the Intent to Treat (ITT) Population which comprised of all enrolled participants who demonstrated use of their primary DPI." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 10 |
| Symbicort Turbuhaler | 40 |
| Seretide Diskus | 26 |
| Spiriva Handihaler | 34 |
| Incruse/Anoro Ellipta | 10 |
| Ultibro/Seebri Breezhaler | 33 |
| Relvar Ellipta+LAMA | 12 |
| Symbicort Turbuhaler+LAMA | 38 |
| Seretide Diskus+LAMA | 26 |
"Participants were asked to demonstrate use of their prescribed DPI at Visit 1 and any error made by the participant was recorded by the HCP in the checklist. Checklist of instructions for correct use were based on the steps for correct use listed in PILs for the respective DPI. The errors made during demonstration by participants were defined as critical, when the participant received a lesser/no dose and non-critical when the dose may not be affected, but the participant has demonstrated improper use of their DPI, as per the PIL. Overall errors is the combination of critical and non-critical errors. The percentage of participants making at least one overall error in either one or both devices (where applicable) is presented." (NCT03114969)
Timeframe: Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Relvar Ellipta | 34 |
| Relvar Ellipta+LAMA | 46 |
Number of participants post-baseline newly occurring or worsening PCS (potentially clinically significant) clinical chemistry values (NCT03262012)
Timeframe: 28 Weeks
| Intervention | Count of Participants (Number) | ||||
|---|---|---|---|---|---|
| ALT >3 x ULN | Total Bilirubin >2 x ULN | Potassium (mmol/L) >6.0 | Glucose (mmol/L) >13.9 if Baseline is ≤10.0 | Glucose (mmol/L) >16.7 if baseline is >10.0 | |
| BFF MDI 320/9.6 ug | 0 | 0 | 0 | 1 | 0 |
| BGF MDI 320/14.4/9.6 ug | 0 | 0 | 2 | 0 | 0 |
| GFF MDI 14.4/9.6 ug | 1 | 0 | 0 | 1 | 1 |
| Symbicort TBH 400/12 ug | 0 | 1 | 0 | 1 | 0 |
Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values (NCT03262012)
Timeframe: 28 Weeks
| Intervention | Participants (Number) | ||||
|---|---|---|---|---|---|
| >=500 if <500 msec at BL and change >=15 msec | >=530 if >=500 msec at BL and >=15 msec | >= 500 msec and >= 15 msec change from BL | Increase from baseline is >=60 msec | Value is >500 msec and increase >=60 msec | |
| BFF MDI 320/9.6 ug | 0 | 0 | 0 | 0 | 0 |
| BGF MDI 320/14.4/9.6 ug | 1 | 0 | 1 | 1 | 0 |
| GFF MDI 14.4/9.6 ug | 0 | 0 | 0 | 1 | 0 |
| Symbicort TBH 400/12 ug | 0 | 0 | 0 | 0 | 0 |
Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs (NCT03262012)
Timeframe: 28 Weeks
| Intervention | Particpants (Number) | |||||
|---|---|---|---|---|---|---|
| Systolic Blood Pressure >=180, Incr >=20 | Systolic Blood Pressure, <=90, Decr >=20 | Diastolic Blood Pressure, >=105 Incr, >=15 | Diastolic Blood Pressure, <=50, Decr >=15 | Tachycardia Event >=110, Incr >=15% | Bradycardia Event <=50, Decr >=15% | |
| BFF MDI 320/9.6 ug | 0 | 1 | 2 | 2 | 2 | 3 |
| BGF MDI 320/14.4/9.6 ug | 3 | 4 | 2 | 4 | 1 | 9 |
| GFF MDI 14.4/9.6 ug | 1 | 1 | 1 | 3 | 0 | 8 |
| Symbicort TBH 400/12 ug | 0 | 1 | 0 | 3 | 0 | 2 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. For Day 2 and Day 85, trough FEV1 was defined as the mean of the 23-hour and 24-hour serial spirometry FEV1 measurements. For Day 28 and Day 84, trough FEV1 was defined as the average of the pre-dose FEV1 measurements recorded before the morning dose of randomized study treatment. Change from Baseline in trough FEV1 was calculated by subtracting post-dose trough FEV1 value from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The treatment effect to be estimated for trough FEV1 was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis. (NCT03478683)
Timeframe: Baseline, Days 2, 28, 84 and 85
| Intervention | Liters (Least Squares Mean) | |||
|---|---|---|---|---|
| Day 2, n=358,359 | Day 28, n=355,353 | Day 84, n=344,340 | Day 85, n=341,337 | |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.018 | -0.015 | -0.018 | -0.012 |
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.008 | 0.046 | 0.040 | 0.026 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.045 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.030 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period on Day 1. Weighted mean change from Baseline on Day 1 was calculated by subtracting weighted mean FEV1 on Day 1 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.054 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.063 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.046 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.032 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.039 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.029 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period on Day 1. Weighted mean change from Baseline on Day 1 was calculated by subtracting weighted mean FEV1 on Day 1 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.045 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.041 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.040 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.023 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. For Day 2 and Day 85, trough FEV1 was defined as the mean of the 23-hour and 24-hour serial spirometry FEV1 measurements. For Day 28 and Day 84, trough FEV1 was defined as the average of the pre-dose FEV1 measurements recorded before the morning dose of randomized study treatment. Change from Baseline in trough FEV1 was calculated by subtracting post-dose trough FEV1 value from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The treatment effect to be estimated for trough FEV1 was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis. (NCT03478696)
Timeframe: Baseline, Days 2, 28, 84 and 85
| Intervention | Liters (Least Squares Mean) | |||
|---|---|---|---|---|
| Day 2, n=355,341 | Day 28, n=353,354 | Day 84, n=346,343 | Day 85, n=343,342 | |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | -0.010 | -0.019 | -0.030 | -0.022 |
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.015 | 0.044 | 0.024 | 0.029 |
Change from baseline in 2-hour post-dose IC following the 1st dose of treatment was defined as the 2-hour post-dose assessment of IC following the 1st dose of treatment (Visit 3 or 5) minus baseline IC. (NCT04078126)
Timeframe: baseline and 2 hours post dose after the first dose of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.264 |
| Symbicort Turbuhaler | 0.258 |
Change from baseline in 2-hour post-dose IC following 1 week of treatment was defined as the 2-hour post-dose assessment of IC following 1 week of treatment minus baseline IC. (NCT04078126)
Timeframe: baseline and 2 hours post dose after 1 week of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.379 |
| Symbicort Turbuhaler | 0.411 |
Change from baseline in pre-dose FEV1 following 1 week of treatment was defined as the 45-minute pre-dose value following 1 week of treatment minus baseline. (NCT04078126)
Timeframe: baseline and after 1 week of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.081 |
| Symbicort Turbuhaler | 0.087 |
Change from baseline in pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment was defined as the pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to no resistance.) (NCT04078126)
Timeframe: baseline and after 1 week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| BFF MDI | 1.50 |
| Symbicort Turbuhaler | 5.11 |
FEV1 AUC0-4 was calculated using the trapezoidal rule and was normalized by dividing by the time in hours from dosing to the last measurement included (typically 4 hours). (NCT04078126)
Timeframe: baseline and 4 hours post dose after 1 week of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.194 |
| Symbicort Turbuhaler | 0.210 |
Change from baseline in 2-hour post-dose FEV1 following the 1st dose of treatment was defined as the 2-hour post-dose assessment of FEV1 following the 1st dose of treatment (Visit 3 or 5) minus baseline FEV1. (NCT04078126)
Timeframe: baseline and 2 hours post dose after the first dose of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.136 |
| Symbicort Turbuhaler | 0.093 |
Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product Turbuhaler S.) (NCT04078126)
Timeframe: baseline and after 1 week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| BFF MDI | 1.13 |
| Symbicort Turbuhaler | 3.82 |
Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product ELLIPTA.) (NCT04078126)
Timeframe: baseline and after 1 week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| BFF MDI | 1.21 |
| Symbicort Turbuhaler | 2.74 |
Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose. (NCT04078126)
Timeframe: baseline and 4 hours post dose after 1 week of treatment
| Intervention | L (Least Squares Mean) |
|---|---|
| BFF MDI | 0.256 |
| Symbicort Turbuhaler | 0.274 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| histamine [no description available] | 4.37 | 1 | 1 | aralkylamino compound; imidazoles | human metabolite; mouse metabolite; neurotransmitter |
| albuterol Albuterol: A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.. albuterol : A member of the class of phenylethanolamines that is 4-(2-amino-1-hydroxyethyl)-2-(hydroxymethyl)phenol having a tert-butyl group attached to the nirogen atom. It acts as a beta-adrenergic agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). | 11.77 | 29 | 11 | phenols; phenylethanolamines; secondary amino compound | beta-adrenergic agonist; bronchodilator agent; environmental contaminant; xenobiotic |
| azathioprine Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). azathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS. | 3.15 | 1 | 0 | aryl sulfide; C-nitro compound; imidazoles; thiopurine | antimetabolite; antineoplastic agent; carcinogenic agent; DNA synthesis inhibitor; hepatotoxic agent; immunosuppressive agent; prodrug |
| terbutaline Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.. terbutaline : A member of the class of phenylethanolamines that is catechol substituted at position 5 by a 2-(tert-butylamino)-1-hydroxyethyl group. | 9.06 | 10 | 8 | phenylethanolamines; resorcinols | anti-asthmatic drug; beta-adrenergic agonist; bronchodilator agent; EC 3.1.1.7 (acetylcholinesterase) inhibitor; hypoglycemic agent; sympathomimetic agent; tocolytic agent |
| prednisolone Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.. prednisolone : A glucocorticoid that is prednisone in which the oxo group at position 11 has been reduced to the corresponding beta-hydroxy group. It is a drug metabolite of prednisone. | 2.11 | 1 | 0 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | adrenergic agent; anti-inflammatory drug; antineoplastic agent; drug metabolite; environmental contaminant; immunosuppressive agent; xenobiotic |
| prednisone Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid. | 3.09 | 1 | 0 | 11-oxo steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | adrenergic agent; anti-inflammatory drug; antineoplastic agent; immunosuppressive agent; prodrug |
| carbostyril Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2. | 2.31 | 1 | 0 | monohydroxyquinoline; quinolone | bacterial xenobiotic metabolite |
| methacholine chloride Methacholine Chloride: A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116) | 3.4 | 1 | 1 | quaternary ammonium salt | |
| soman Soman: An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent. | 2.08 | 1 | 0 | phosphonic ester | |
| quinuclidines Quinuclidines: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms and contains an amine group. | 4.94 | 2 | 1 | quinuclidines; saturated organic heterobicyclic parent | |
| diphenhydramine hydrochloride Antitussive Agents: Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally.. diphenhydramine hydrochloride : The hydrochloride salt of diphenhydramine. | 5.42 | 2 | 2 | hydrochloride; organoammonium salt | anti-allergic agent; antiemetic; antiparkinson drug; antipruritic drug; H1-receptor antagonist; local anaesthetic; muscarinic antagonist; sedative |
| alpha-aminopyridine alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups. | 3.51 | 1 | 1 | ||
| glycopyrrolate Glycopyrrolate: A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics.. glycopyrronium bromide : A quaternary ammonium salt composed of 3-{[cyclopentyl(hydroxy)phenylacetyl]oxy}-1,1-dimethylpyrrolidin-1-ium and bromide ions in a 1:1 ratio. | 5.34 | 5 | 2 | organic bromide salt; quaternary ammonium salt | |
| acetylcysteine N-acetyl-L-cysteine : An N-acetyl-L-amino acid that is the N-acetylated derivative of the natural amino acid L-cysteine. | 2.13 | 1 | 0 | acetylcysteine; L-cysteine derivative; N-acetyl-L-amino acid | antidote to paracetamol poisoning; antiinfective agent; antioxidant; antiviral drug; ferroptosis inhibitor; geroprotector; human metabolite; mucolytic; radical scavenger; vulnerary |
| fluorescein Fluorescein: A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor.. fluorescein (lactone form) : A xanthene dye that is highly fluorescent, detectable even when present in minute quantities. Used forensically to detect traces of blood, in analytical chemistry as an indicator in silver nitrate titrations and in microscopy. | 2.11 | 1 | 0 | 2-benzofurans; gamma-lactone; organic heteropentacyclic compound; oxaspiro compound; polyphenol; xanthene dye | fluorescent dye; radioopaque medium |
| phenyl acetate phenyl acetate: The ester formed between phenol and acetic acid. Don't confuse with phenylacetic acid derivatives listed under PHENYLACETATES.. phenyl acetate : An acetate ester obtained by the formal condensation of phenol with acetic acid. | 5.35 | 4 | 1 | benzenes; phenyl acetates | |
| salmeterol xinafoate Salmeterol Xinafoate: A selective ADRENERGIC BETA-2 RECEPTOR agonist that functions as a BRONCHODILATOR when administered by inhalation. It is used to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE. | 5.26 | 6 | 0 | naphthoic acid | |
| methotrexate [no description available] | 3.15 | 1 | 0 | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent |
| mometasone furoate Mometasone Furoate: A pregnadienediol derivative ANTI-ALLERGIC AGENT and ANTI-INFLAMMATORY AGENT that is used in the management of ASTHMA and ALLERGIC RHINITIS. It is also used as a topical treatment for skin disorders. | 4.83 | 3 | 0 | 11beta-hydroxy steroid; 2-furoate ester; 20-oxo steroid; 3-oxo-Delta(1),Delta(4)-steroid; organochlorine compound; steroid ester | anti-allergic agent; anti-inflammatory drug |
| mycophenolic acid Mycophenolic Acid: Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.. mycophenolate : A monocarboxylic acid anion resulting from the removal of a proton from the carboxy group of mycophenolic acid.. mycophenolic acid : A member of the class of 2-benzofurans that is 2-benzofuran-1(3H)-one which is substituted at positions 4, 5, 6, and 7 by methyl, methoxy, (2E)-5-carboxy-3-methylpent-2-en-1-yl, and hydroxy groups, respectively. It is an antibiotic produced by Penicillium brevi-compactum, P. stoloniferum, P. echinulatum and related species. An immunosuppressant, it is widely used (partiularly as its sodium salt and as the 2-(morpholin-4-yl)ethyl ester prodrug, mycophenolate mofetil) to prevent tissue rejection following organ transplants and for the treatment of certain autoimmune diseases. | 2.31 | 1 | 0 | 2-benzofurans; gamma-lactone; monocarboxylic acid; phenols | anticoronaviral agent; antimicrobial agent; antineoplastic agent; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; environmental contaminant; immunosuppressive agent; mycotoxin; Penicillium metabolite; xenobiotic |
| roflumilast [no description available] | 3.51 | 1 | 1 | aromatic ether; benzamides; chloropyridine; cyclopropanes; organofluorine compound | anti-asthmatic drug; phosphodiesterase IV inhibitor |
| capsaicin ALGRX-4975: an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief. capsaicinoid : A family of aromatic fatty amides produced as secondary metabolites by chilli peppers. | 4.72 | 1 | 1 | capsaicinoid | non-narcotic analgesic; TRPV1 agonist; voltage-gated sodium channel blocker |
| rhodamine 123 Rhodamine 123: A fluorescent probe with low toxicity which is a potent substrate for ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 in both normal and malignant cells. (Leukemia 1997;11(7):1124-30). rhodamine 123(1+) : A cationic fluorescent dye derived from 9-phenylxanthene. | 2.11 | 1 | 0 | organic cation; xanthene dye | fluorochrome |
| pulmicort Budesonide: A glucocorticoid used in the management of ASTHMA, the treatment of various skin disorders, and allergic RHINITIS.. budesonide : A glucocorticoid steroid having a highly oxygenated pregna-1,4-diene structure. It is used mainly in the treatment of asthma and non-infectious rhinitis and for treatment and prevention of nasal polyposis. | 18.44 | 116 | 46 | 11beta-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; cyclic acetal; glucocorticoid; primary alpha-hydroxy ketone | anti-inflammatory drug; bronchodilator agent; drug allergen |
| montelukast montelukast: a leukotriene D4 receptor antagonist | 5.35 | 4 | 1 | aliphatic sulfide; monocarboxylic acid; quinolines | anti-arrhythmia drug; anti-asthmatic drug; leukotriene antagonist |
| clobetasol Clobetasol: A derivative of PREDNISOLONE with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than FLUOCINONIDE, it is used topically in treatment of PSORIASIS but may cause marked adrenocortical suppression.. clobetasol : A 3-oxo-Delta(1),Delta(4)-steroid that is 16beta-methylpregna-1,4-diene-3,20-dione bearing hydroxy groups at the 11beta and 17alpha positions, fluorine at position 9, and a chlorine substituent at position 21. It is used as its 17alpha-propionate ester to treat various skin disorders, including exzema and psoriasis. | 3.15 | 1 | 0 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 3-oxo-Delta(1),Delta(4)-steroid; chlorinated steroid; fluorinated steroid; glucocorticoid; tertiary alpha-hydroxy ketone | anti-inflammatory drug; SMO receptor agonist |
| fluticasone Fluticasone: A STEROID with GLUCOCORTICOID RECEPTOR activity that is used to manage the symptoms of ASTHMA; ALLERGIC RHINITIS, and ATOPIC DERMATITIS.. fluticasone : A trifluorinated corticosteroid used in the form of its propionate ester for treatment of allergic rhinitis. | 9.8 | 11 | 2 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 3-oxo-Delta(4) steroid; corticosteroid; fluorinated steroid; thioester | anti-allergic agent; anti-asthmatic drug |
| fumarates Fumarates: Compounds based on fumaric acid.. fumarate(2-) : A C4-dicarboxylate that is the E-isomer of but-2-enedioate(2-) | 2.82 | 2 | 0 | butenedioate; C4-dicarboxylate | human metabolite; metabolite; Saccharomyces cerevisiae metabolite |
| tiotropium bromide Tiotropium Bromide: A scopolamine derivative and CHOLINERGIC ANTAGONIST that functions as a BRONCHODILATOR AGENT. It is used in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.. tiotropium bromide : An organic bromide salt having (1alpha,2beta,4beta,5alpha,7beta)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0(2,4)]nonane as the counterion. Used (in the form of the hydrate) for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease. | 9.48 | 10 | 3 | ||
| fluticasone furoate fluticasone furoate: a glucocorticoid; structure in first source. fluticasone furoate : A trifluorinated corticosteroid that consists of 6alpha,9-difluoro-11beta,17alpha-dihydroxy-17beta-{[(fluoromethyl)sulfanyl]carbonyl}-16-methyl-3-oxoandrosta-1,4-diene bearing a 2-furoyl substituent at position 17. Used in combination with vilanterol trifenate for treatment of bronchospasm associated with chronic obstructive pulmonary disease. | 4.22 | 2 | 0 | 11beta-hydroxy steroid; 2-furoate ester; 3-oxo-Delta(1),Delta(4)-steroid; corticosteroid; fluorinated steroid; steroid ester; thioester | anti-allergic agent; anti-asthmatic drug; prodrug |
| vilanterol [no description available] | 6.27 | 3 | 1 | benzyl alcohols; dichlorobenzene; ether; phenols; secondary amino compound | beta-adrenergic agonist; bronchodilator agent |
| gsk573719 GSK573719: Muscarinic Antagonist. umeclidinium : A quaternary ammonium ion that is quinuclidine substituted at positions 1 and 4 by 2-(benzyloxy)ethyl and hydroxy(diphenyl)methyl groups respectively. | 4.94 | 2 | 1 | ||
| dextrothyroxine [no description available] | 3.15 | 1 | 0 | ||
| (9R)-9-chloro-11,17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of ASTHMA.. beclomethasone : A 17alpha-hydroxy steroid that is prednisolone in which the hydrogens at the 9alpha and 16beta positions are substituted by a chlorine and a methyl group, respectively. | 6.74 | 8 | 1 | 21-hydroxy steroid | |
| combivent respimat Albuterol, Ipratropium Drug Combination: A combined pharmaceutical preparation of Ipratropium Bromide and Albuterol Sulfate that is used to treat the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE. | 2.08 | 1 | 0 | ||
| interleukin-8 Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. | 6.46 | 3 | 3 | ||
| fluticasone propionate, salmeterol xinafoate drug combination Fluticasone-Salmeterol Drug Combination: A drug combination of fluticasone and salmeterol that is used as an inhaler formulation to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE. | 14.13 | 43 | 17 | ||
| mometasone furoate, formoterol fumarate drug combination Mometasone Furoate, Formoterol Fumarate Drug Combination: A pharmaceutical preparation of mometasone furoate and formoterol fumarate that is used as an inhaled dosage form for the treatment of ASTHMA. | 7.06 | 4 | 3 | ||
| cyclosporine Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). | 3.15 | 1 | 0 | ||
| exudates Malaysia: A parliamentary democracy with a constitutional monarch in southeast Asia, consisting of 11 states (West Malaysia) on the Malay Peninsula and two states (East Malaysia) on the island of BORNEO. It is also called the Federation of Malaysia. Its capital is Kuala Lumpur. Before 1963 it was the Union of Malaya. It reorganized in 1948 as the Federation of Malaya, becoming independent from British Malaya in 1957 and becoming Malaysia in 1963 as a federation of Malaya, Sabah, Sarawak, and Singapore (which seceded in 1965). The form Malay- probably derives from the Tamil malay, mountain, with reference to its geography. (From Webster's New Geographical Dictionary, 1988, p715 & Room, Brewer's Dictionary of Names, 1992, p329) | 3.85 | 2 | 1 |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Asthma, Bronchial [description not available] | 0 | 19.14 | 140 | 58 |
| Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). | 0 | 19.14 | 140 | 58 |
| Carcinoma, Non-Small Cell Lung [description not available] | 0 | 4.85 | 2 | 1 |
| Cancer of Lung [description not available] | 0 | 4.85 | 2 | 1 |
| Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. | 0 | 4.85 | 2 | 1 |
| Lung Neoplasms Tumors or cancer of the LUNG. | 0 | 4.85 | 2 | 1 |
| Airflow Obstruction, Chronic [description not available] | 0 | 16.13 | 74 | 25 |
| Pulmonary Hypertension [description not available] | 0 | 2.41 | 1 | 0 |
| Centriacinar Emphysema [description not available] | 0 | 2.72 | 2 | 0 |
| Emphysema A pathological accumulation of air in tissues or organs. | 0 | 2.41 | 1 | 0 |
| Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES. | 0 | 2.41 | 1 | 0 |
| Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA. | 0 | 16.13 | 74 | 25 |
| Innate Inflammatory Response [description not available] | 0 | 7.11 | 4 | 3 |
| Cough A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs. | 0 | 5.42 | 2 | 2 |
| Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. | 0 | 7.11 | 4 | 3 |
| Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Syndrome with clinical features of both ASTHMA and COPD. | 0 | 4.15 | 2 | 1 |
| Bronchiolitis, Exudative [description not available] | 0 | 2.63 | 2 | 0 |
| Bronchiolitis Obliterans Inflammation of the BRONCHIOLES leading to an obstructive lung disease. Bronchioles are characterized by fibrous granulation tissue with bronchial exudates in the lumens. Clinical features include a nonproductive cough and DYSPNEA. | 0 | 2.63 | 2 | 0 |
| Cystic Fibrosis of Pancreas [description not available] | 0 | 2.6 | 1 | 0 |
| Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION. | 0 | 2.6 | 1 | 0 |
| Blood Poisoning [description not available] | 0 | 2.21 | 1 | 0 |
| Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK. | 0 | 2.21 | 1 | 0 |
| Chronic Illness [description not available] | 0 | 3.17 | 1 | 0 |
| Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). | 0 | 3.17 | 1 | 0 |
| Dermatitis Medicamentosa [description not available] | 0 | 2.25 | 1 | 0 |
| Contact Dermatitis [description not available] | 0 | 2.25 | 1 | 0 |
| Dermatitis, Contact A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. | 0 | 2.25 | 1 | 0 |
| Complications, Pregnancy [description not available] | 0 | 2.61 | 2 | 0 |
| Cold Panniculitis [description not available] | 0 | 2.25 | 1 | 0 |
| Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. | 0 | 2.61 | 2 | 0 |
| alpha 1-Antitrypsin Deficiency Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS. | 0 | 2.25 | 1 | 0 |
| Koch's Disease [description not available] | 0 | 2.25 | 1 | 0 |
| Tuberculosis Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS. | 0 | 2.25 | 1 | 0 |
| Disease Exacerbation [description not available] | 0 | 13.24 | 25 | 15 |
| Genetic Diseases, X-Chromosome Linked [description not available] | 0 | 2.31 | 1 | 0 |
| Autoimmune Diabetes [description not available] | 0 | 2.31 | 1 | 0 |
| Diseases of Immune System [description not available] | 0 | 2.31 | 1 | 0 |
| Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. | 0 | 2.31 | 1 | 0 |
| Diarrhea An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight. | 0 | 2.31 | 1 | 0 |
| Immune System Diseases Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both. | 0 | 2.31 | 1 | 0 |
| Experimental Lung Inflammation Inflammation of any part, segment or lobe, of the lung parenchyma. | 0 | 3.04 | 4 | 0 |
| Pneumonia Infection of the lung often accompanied by inflammation. | 0 | 3.04 | 4 | 0 |
| Airway Remodeling The structural changes in the number, mass, size and/or composition of the airway tissues. | 0 | 3.09 | 1 | 0 |
| Airway Obstruction Any hindrance to the passage of air into and out of the lungs. | 0 | 5.85 | 4 | 2 |
| Breathlessness [description not available] | 0 | 5.67 | 3 | 2 |
| Dyspnea Difficult or labored breathing. | 0 | 5.67 | 3 | 2 |
| Abnormalities, Congenital [description not available] | 0 | 2.17 | 1 | 0 |
| Infantile Respiratory Distress Syndrome [description not available] | 0 | 2.17 | 1 | 0 |
| Respiratory Distress Syndrome, Newborn A condition of the newborn marked by DYSPNEA with CYANOSIS, heralded by such prodromal signs as dilatation of the alae nasi, expiratory grunt, and retraction of the suprasternal notch or costal margins, mostly frequently occurring in premature infants, children of diabetic mothers, and infants delivered by cesarean section, and sometimes with no apparent predisposing cause. | 0 | 2.17 | 1 | 0 |
| Cataract, Membranous [description not available] | 0 | 3.59 | 1 | 1 |
| Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed) | 0 | 3.59 | 1 | 1 |
| Intraocular Pressure The pressure of the fluids in the eye. | 0 | 3.95 | 2 | 1 |
| Lung Injury, Acute [description not available] | 0 | 2.08 | 1 | 0 |
| Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. | 0 | 2.08 | 1 | 0 |
| Acute Lung Injury A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological). | 0 | 2.08 | 1 | 0 |
| Symptom Cluster [description not available] | 0 | 2.11 | 1 | 0 |
| Syndrome A characteristic symptom complex. | 0 | 2.11 | 1 | 0 |
| Acute Symptom Flare [description not available] | 0 | 4.43 | 1 | 1 |
| Apoplexy [description not available] | 0 | 2.11 | 1 | 0 |
| Cardiovascular Diseases Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM. | 0 | 2.11 | 1 | 0 |
| Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) | 0 | 2.11 | 1 | 0 |
| Cranial Nerve II Diseases [description not available] | 0 | 2.13 | 1 | 0 |
| Retinal Pigment Epithelial Detachment [description not available] | 0 | 2.13 | 1 | 0 |
| Posterior Vitreous Detachment [description not available] | 0 | 2.13 | 1 | 0 |
| Congenital X-Linked Retinoschisis [description not available] | 0 | 2.13 | 1 | 0 |
| Glaucoma An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed) | 0 | 2.13 | 1 | 0 |
| Optic Nerve Diseases Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. | 0 | 2.13 | 1 | 0 |
| Retinal Detachment Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). | 0 | 2.13 | 1 | 0 |
| Chronic Bronchitis [description not available] | 0 | 3.51 | 1 | 1 |
| Bronchitis, Chronic A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. | 0 | 3.51 | 1 | 1 |
| Anoxemia [description not available] | 0 | 4.45 | 1 | 1 |
| Acute Respiratory Distress Syndrome [description not available] | 0 | 4.45 | 1 | 1 |
| Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. | 0 | 4.45 | 1 | 1 |
| Respiratory Distress Syndrome A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA. | 0 | 4.45 | 1 | 1 |
| Obstructive Lung Diseases [description not available] | 0 | 3.43 | 1 | 1 |
| Lung Diseases, Obstructive Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent. | 0 | 3.43 | 1 | 1 |
| Hyperkinetic Dysphonia [description not available] | 0 | 2.06 | 1 | 0 |
| Dysphonia Difficulty and/or pain in PHONATION or speaking. | 0 | 2.06 | 1 | 0 |
| Recrudescence [description not available] | 0 | 2.97 | 1 | 0 |
| Bone Fractures [description not available] | 0 | 2.05 | 1 | 0 |
| Fractures, Bone Breaks in bones. | 0 | 2.05 | 1 | 0 |
| Smoking Cessation Discontinuing the habit of SMOKING. | 0 | 4.37 | 1 | 1 |
| Creeping Eruption [description not available] | 0 | 2.97 | 1 | 0 |
| Eosinophilia, Pulmonary [description not available] | 0 | 2.97 | 1 | 0 |
| Pulmonary Eosinophilia A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents. | 0 | 2.97 | 1 | 0 |
| Respiratory Tract Diseases Diseases involving the RESPIRATORY SYSTEM. | 0 | 2.03 | 1 | 0 |
| Angiogenesis, Pathologic [description not available] | 0 | 2.04 | 1 | 0 |