Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-center, Randomized, Double-blind, Dose-ranging Study to Evaluate GSK573719 in Combination With Fluticasone Furoate, Fluticasone Furoate Alone, and an Active Control of Fluticasone Furoate/Vilanterol Combination in Subjects With Asthma
Brief Summary: Brief Summary: The purpose of this study is to characterize the dose response of GSK573719 in combination with Fluticasone furoate 100mcg in patients with asthma. Treatment with inhaled Fluticasone furoate and Fluticasone furoate/Vilanterol are included as an active control.

Detailed Description: Long acting muscarinic receptor antagonists (anti-cholinergic bronhcodilator) exert their effects via distinct and complementary bronchodilator mechanisms on large and small airways. Most of the experience with older anti-cholinergics had been with acute use and little is known about their effect in chronic use in asthma. This is a multicenter, randomized, double-blind, crossover study to evaluate 5 doses of inhaled GSK573719 inhaled over 14 days in patients with asthma. Fluticasone furoate (100 mcg) and Fluticasone furoate/Vilanterol (100/59mcg) will be included as an active comparator. Each eligible subject will receive a sequence of 3 of 7 potential treatments for a total of 3 treatment periods per subject. The total duration of subject participation is approximately 14 weeks.


Options:
A: Inclusion criteria:

1. All patients must sign and date an Informed Consent Form consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice ( ICH-GCP) guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
2. Male or female patients aged at least 18 years but not more than 75 years.
3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility resulting in a Forced Expiratory Volume in 1 Second (FEV1) increase of equal above 12% and equal above 200mL.
4. The initial diagnosis of asthma must have been made before the patient's age of 40.
5. All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of inhaled corticosteroids.
6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (alone or in a fixed combination with a Long Acting Betaadrenergic (LABA) or Short Acting Betaadrenergic (SABA)) for at least 4 weeks prior to Visit 1.
7. All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an Asthma Control Questionnaire (ACQ) Score
8. All patients must have a pre-bronchodilator FEV1 above equal 60% predicted and below equal 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Coal and Steel Community Guidelines (ECSC).
9. All patients must have an increase in FEV1 of equal above 12% and equal above 200 mL 15 minutes after 400 µg salbutamol at Visit 1.
10. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30% .
11. Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment and who have a smoking history of less than 10 pack years.
12. Patients must be able to use the Respimat® inhaler correctly.
13. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the e-Diary/peak flow meter.
14. Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration).

Exclusion criteria:

1. Patients with a significant disease other than asthma.A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
2. Patients with a clinically relevant abnormal screening hematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion no. 1.
3. Patients with a recent history (i.e. six months or less) of myocardial infarction.
4. Patients who have been hospitalised for cardiac failure during the past year.
5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
6. Patients with lung diseases other than asthma (e.g. Chronic Obstructive Lung Disease (COPD)).
7. Patients with known active tuberculosis.
8. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.
9. Patients who have undergone thoracotomy with pulmonary resection.
10. Patients with significant alcohol or drug abuse within the past two years.
11. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to V 1.
12. Patients with known hypersensitivity to anticholinergic drugs, Benzalconiumchloride (BAC), Ethylenediaminetetraacetate (EDTA) or any other components of the study medication delivery systems.
13. Pregnant or nursing women.
14. Women of childbearing potential not using a highly effective method of birth control.
15. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 or during the screening period. Topical cardio-selective beta-blocker eye medications for non-arrow angle glaucoma are allowed.
16. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 or during the screening period.
17. Patients who have been treated with oral beta-adrenergics within four weeks prior to Visit 1 or during the screening period.
18. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 or during the screening period.
19. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®), within 6 months prior to Visit 1 or during the screening period.20. Patients who have been treated with cromolyn sodium or nedocromil sodium within two weeks prior to Visit 1 or during the screening period.

21. Patients who have been treated with methylxanthines within two weeks prior to Visit 1 or during the screening period.

22. Patients who have taken an investigational drug within four weeks prior to Visit 1.

23. Patients who have been treated with other non-approved and according to international guidelines not recommended "experimental" drugs for routine asthma therapy (e.g. TNFalpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1 or during the screening period.

24. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period. Visit 1 and/or Visit 2 should be postponed in case of an asthma exacerbation or respiratory tract infection.

25. Patients who have previously been randomised in this trial or are currently participating in another trial.

26.Patients who have been treated with depot corticosteroids within six months prior to Visit 1 or during the screening period.

27.Patients who have been treated with leukotriene modifiers within two weeks prior to Visit 1 or during the screening period.
B: Inclusion criteria:

1. All patients must sign and date an Informed Consent Form consistent with the Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
2. Male or female patients aged between 18 and 75 years (at date of informed consent).
3. All patients must have at least a 3 month history of asthma at the time of enrolment into the trial. The diagnosis should be confirmed at Visit 1 by fulfilling inclusion criterion no. 5.
4. The initial diagnosis of asthma must have been made before the patient's age of 40.
5. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 to 30 minutes after 4 puffs of 100 µg salbutamol) resulting in a Forced Expiratory Volume in one second (FEV1) increase of = 12% and = 200mL.
6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (alone or in a fixed combination with a long acting or short acting beta agonist \[LABA or SABA\]) for at least 4 weeks prior to Visit 1.
7. All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of = 1.5.
8. All patients must have a pre-bronchodilator FEV1 = 60% and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Community for Steel and Coal (ECSC).
9. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
10. Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.
11. Patients must be able to use the Respimat® inhaler correctly.
12. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion criteria:

1. Patients with a significant disease other than asthma.
2. Patients with a clinically relevant abnormal screening (Visit 1) haematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion 1.
3. Patients with a recent history (i.e. six months or less) of myocardial infarction.
4. Patients who have been hospitalised for cardiac failure during the past year.
5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
6. Patients with lung diseases other than asthma.
7. Patients with known active tuberculosis.
8. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
9. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.
10. Patients with known moderate to severe renal impairment.
11. Patients with known narrow angle glaucoma or any other disease where anticholinergic treatment is contraindicated.
12. Patients with significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.
13. Patients with significant alcohol or drug abuse within the past two years (to the discretion of the investigator).
14. Patients who are currently in a pulmonary rehabilitation program or have completed pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening) or who will start a rehabilitation program during the study.
15. Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetate (EDTA) or any other components of the study medication delivery system (Respimat®/ tiotropium inhalation solution).
16. Pregnant or nursing woman.
17. Women of childbearing potential not using a highly effective method of birth control.
18. Patients who have taken an investigational drug within four weeks prior to Visit 1.
19. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). Topical cardio-selective beta-blocker eye medications for non-arrow angle glaucoma are allowed.
20. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
21. Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period (period between Visit 1 and Visit 2)
22. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period.
23. Patients who have been treated with anti-Immunoglobuline E (anti-IgE) antibodies, e.g. omalizumab, within 6 months prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
24. Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
25. Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
26. Patients who have been treated with other non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy (e.g. Tumor Necrosis Factor (TNF)-alpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
27. Patient with any asthma exacerbation or respiratory tract infection in the 4 weeks prior to visit 1 and/or during the screening period.
C: Inclusion Criteria:

* Outpatient
* 18 years of age or older at Visit 1
* Diagnosis of Asthma
* Male or eligible Female
* Pre-bronchodilator FEV1 of 40-80% of the predicted normal value at Visit 1
* Demonstrated reversibility by ≥12% and ≥200mL of FEV1 within 40 minutes following albuterol at Visit 1
* A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long-acting beta-agonist, or leukotriene modifier etc.,) for a minimum of 8 weeks prior to Visit 1.

Exclusion Criteria:

* History of Life threatening asthma
* Respiratory infection not resolved
* Asthma exacerbation
* Concurrent respiratory disease
* Current Smokers
* Other diseases that are uncontrolled disease or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
* A positive Hepatitis B surface antigen or positive Hepatitis C antibody and/or HIV
* Visual clinical evidence of oropharyngeal candidiasis
* Drug or milk protein allergies
* Concomitant medications affecting course of asthma
* Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
* Previous use of GSK573719
* Any disease preventing use of anticholinergics
* Any condition that impairs compliance with study protocol including visit schedule and completion of daily diaries
* Any subject with a history of alcohol or substance abuse
* Any affiliation with Investigator's site
D: Inclusion_Criteria:

1. Patients homozygous for arginine at the 16th amino acid position of the beta2 adrenergic receptor (B16 Arg/Arg)
2. All patients must sign and date an Informed Consent Form for the study prior to participation in the trial
3. Male or female outpatients with at least 18 years of age, but not older than 65 years
4. Patients must have a documented history of asthma
5. Patients must be current non-smokers or ex-smokers with a cigarette smoking history of \<10 pack-years
6. Patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent

Exclusion_Criteria:

1. Patients with a significant disease other than asthma
2. Patients with a recent history (i.e., six months or less) of myocardial infarction
3. Patients who have been hospitalized for heart failure (New York Heart Association class III or IV) within the past year
4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year
5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.
6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD)
7. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
8. Patients with known active tuberculosis
9. Patients who have undergone thoracotomy with pulmonary resection.
10. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to visit 1 or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study.

Answer: C