Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Double-dummy, Parallel-group Multicentre Study to Assess Efficacy and Safety of Fluticasone Furoate/GW642444 Inhalation Powder and Fluticasone Propionate/Salmeterol Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents
Brief Summary: The purpose of the study is to compare the efficacy and safety of fluticasone furoate/vilanterol (GW642444) inhalation powder administered once daily with fluticasone propionate/salmeterol administered twice daily in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24-week period.


Options:
A: Inclusion Criteria:

* Diagnosis of asthma and baseline lung function tests, symptoms and medication use as determined by the protocol
* Required and received treatment with inhaled corticosteroids within the timeframe and doses specified in the protocol

Exclusion Criteria:

* Has required treatment with non-inhaled corticosteroids within previous 30 days, has sensitivity to drugs specified in the protocol or requires treatment with a beta-blocker.
* Has had cancer within previous 5 years or has a condition that may put the patient at risk in this study.
B: Inclusion criteria:

1. All patients and their parent(s) (or legally accepted representative) must sign and date respectively an informed assent and an informed consent consistent with International Conference on Harmonisation - Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to the patient's participation in the trial. A separate informed consent/assent is required for pharmacogenomic sampling.
2. Male or female patients between 12 and 17 years of age (at date of informed consent/assent).
3. All patients must have at least a 3-month history of asthma at the time of enrolment into the trial.
4. All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication, OR at stable medium dose in combination with two other controller medications, for at least 4 weeks before Visit 1.
5. 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.
6. All patients must have a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) = 60% and = 90% of predicted normal at Visit 1.
7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.
8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of = 12% and = 200 mL 15 to 30 minutes after 400 µg salbutamol (albuterol). If patients in the lower age range (e.g. 12 to 14 year old patients) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (=12%) post-bronchodilator response.
9. All patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
10. Patients must be able to use the Respimat® inhaler correctly.
11. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres according to American Thoracic Society/ European Respiratory Society (ATS/ERS) standards and use of the electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion criteria:

1. Significant disease other than asthma.
2. Abnormal haematology or blood chemistry.
3. History of heart disease, and/or hospitalised for cardiac syncope or failure.
4. Any unstable or life-threatening or requiring intervention or cardiac arrhythmia.
5. Malignancy for which the patient has undergone resection, radiation therapy or chemotherapy.
6. Active tuberculosis.
7. Alcohol or drug abuse.
8. Thoracotomy with pulmonary resection.
9. Pulmonary rehabilitation program.
10. Hypersensitivity to anticholinergic drugs, or any components of the study medication delivery system.
11. Pregnant or nursing adolescent female patients.
12. Female patients of child-bearing potential not using a highly effective method of birth control.
13. Investigational drug within four weeks or six half lives prior to Visit 1.
14. Long-acting anticholinergics within four weeks prior to Visit 1.
15. Systemic corticosteroids at a high dose or at a not stable low dose within four weeks prior to Visit 1.
16. Leukotriene modifiers if not stabilised for at least four weeks prior to Visit 1.
17. Long-acting theophylline preparations if not stabilised for at least two weeks prior to Visit 1.
18. Anti Immunoglobulin E (Anti-IgE) treatment if not stabilised for at least six months prior to Visit 1.
19. Cromones if not stabilised within four weeks prior to Visit 1.
20. Oral beta-blocker medication within four weeks prior to Visit 1.
21. Systemic oral or i.v. or s.c. beta-adrenergics within four weeks prior to Visit 1.
22. Other non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy within four weeks prior to Visit 1.
23. Any acute asthma exacerbation or respiratory tract infection in the four weeks prior to Visit 1and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
24. Randomised in this trial or currently participating in another trial.
25. Narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
26. Moderate to severe renal impairment.
27. Patients requiring 10 or more puffs of rescue medication per day on more than 2 consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.
C: Inclusion Criteria:

* Clinical diagnosis of asthma
* Reversibility of at least 12% and at least 200mLs within 10-40 minutes following 2-4 inhalations of albuterol
* FEV1 of 40-85% predicted normal
* Currently using inhaled corticosteroid therapy

Exclusion Criteria:

* History of life-threatening asthma within previous 5 years (requiring intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxic seizures)
* Respiratory infection or oral candidiasis
* Asthma exacerbation requiring oral corticosteroids or that resulted in overnight hospitalisation requiring additional asthma treatment
* Uncontrolled disease or clinical abnormality
* Allergies
* Taking another investigational medication or prohibited medication
* Night shift workers
* Current smokers or subjects with smoking history of at least 10 pack years
D: Inclusion criteria:

1. All patients must sign and date an Informed Consent Form consistent with 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 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.
4. All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent
5. All patients must have a history of one or more asthma exacerbation in the past year.
6. Patients must have evidence of treated, severe, persistent asthma in postbronchodilator pulmonary function tests.
7. Patients should 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
8. Patients must be able to use the Respimat® inhaler correctly
9. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the electronic diary/peak flow meter.

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 clinically relevant abnormal screening haematology or blood chemistry.
3. Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, 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.
4. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
5. Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.
6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
7. Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.
8. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.
9. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.
10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.
11. Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.
12. Patients with a known narrow-angle glaucoma.

Note:

As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.

As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of \<= 50 mL/min) treated with tiotropium should be monitored closely.

Answer: C