Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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) (Budesonide) and a Long Acting β2-agonist (LABA) (Formoterol) as Compared to Treatment With ICS (Budesonide) Alone in Adult and Adolescent (≥12 Years of Age) Patients With Asthma
Brief Summary: The purpose of the study is to evaluate the safety of Symbicort compared to inhaled corticosteroid alone during 6 months in adult and adolescent patients with asthma


Options:
A: Inclusion Criteria:

* Outpatient at least 12 years of age
* Both genders; females of childbearing potential must be willing to use birth control method
* Clinical diagnosis of asthma for ≥12 weeks
* Best pre-bronchodilator FEV1 of 40%-90% predicted
* Reversibility of FEV1 of at least 12% and 200mls
* Current asthma therapy that include an inhaled corticosteroid for at least 12 weeks prior to 1st visit
* Ability to use replace current short-acting rescue treatment with albuterol and ability to withhold albuterol use for at least 6 hours prior to study visits

Exclusion Criteria:

* History of life-threatening asthma
* Respiratory infection within last 4 weeks leading to change in asthma management
* Asthma exacerbation within last 3 months
* Concurrent respiratory disease or other disease that would confound study participation or affect subject safety
* Allergies to study drugs, study drugs' excipients, or medications related to study drugs
* Taking another investigational medication or medication prohibited for use during the study.
* Previous participation in a vilanterol (GW642444) study
B: Inclusion Criteria:

* Clinical diagnosis of moderate to severe persistent asthma for at least 6 months, according to GINA revised version 2002 guidelines (11):

  * Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ³ 50% and £ 80% of the predicted normal;
  * Asthma not adequately controlled with the current therapies, defined as presence of daily asthma symptoms \> once a week and night-time asthma symptoms \> twice a month, and daily use of short-acting β2-agonists. These findings are to be based on recent medical history and are to be confirmed in the 2-week run-in period.
* Treatment with inhaled corticosteroids at a daily dose ≤ 1000 μg of BDP or equivalent. The daily dose of inhaled corticosteroids taken at visit 1 will be assessed taking into account the following ratios between the doses of the different steroids: fluticasone propionate : BDP CFC = 1 : 2; budesonide : BDP CFC = 4 : 5; flunisolide : BDP CFC = 1 : 1. The ratios between inhaled steroids are irrespective of the formulations (i.e. spray aerosol or powder) used. When BDP is given in the new extra-fine HFA-134a formulation (as QVAR®, 3M Healthcare), the ratio with BDP CFC is set as 2 : 5. Therefore, the maximum allowed daily dose of inhaled corticosteroids at study entry will be: budesonide 800 μg, fluticasone propionate 500 μg, flunisolide 1000 μg, BDP 1000 mg, BDP HFA extra-fine 400 μg.
* Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200mL) from baseline value in the measurement of FEV1 30 minutes following 2 puffs (2 ´ 100 µg) of inhaled salbutamol administered via pMDI. The reversibility test can be avoided in patients having a documented positive response in the previous 6 months.
* A co-operative attitude and ability to be trained to correctly use the metered dose inhalers and to complete the diary cards.
* Written informed consent obtained.
* At the end of the 2-week run-in period, the presence of daily asthma symptoms (of at least mild intensity) and nighttime asthma symptom (of at least mild intensity) \> once a week, as well as of daily use of relief salbutamol is to be confirmed by reviewing the diary cards for run-in.

Exclusion Criteria:

* Inability to carry out pulmonary function testing;
* Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the National Heart Lung and Blood Institute/World Health Organisation (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (30);
* History of near fatal asthma;
* Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 8 weeks;
* Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months;
* Patients treated with long-acting β2-agonists, anticholinergics and antihistamines during the previous 2 weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks;
* Patients who have changed their dose of inhaled corticosteroids during the previous 4 weeks, or treatment with inhaled corticosteroids at a daily dose \> 1000 μg of BDP or equivalent (except for extra-fine formulations, see inclusion criteria);
* Current smokers or recent (less than one year) ex-smokers, defined as smoking at least 10 cigarettes/day;
* History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias;
* Diabetes mellitus;
* Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous six months;
* Patients with an abnormal QTc interval value in the ECG test, defined as \> 450 msec in males or \> 470 msec in females;
* Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree;
* Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases;
* Cancer or any chronic diseases with prognosis \< 2 years;
* Pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization). A pregnancy test is to be carried out in women of a fertile age.
* History of alcohol or drug abuse;
* Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use;
* Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;
* Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
* Patients who received any investigational new drug within the last 12 weeks;
* Patients who have been previously enrolled in this study;
* At the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of PEFR (L/sec) measured at the clinics at the end of the run-in period ³ 15% in respect of values measured at the start of the run-in period;
* Patients with asthma exacerbations during the run-in period will also be excluded from the study.
C: Inclusion Criteria:

* Provision of signed informed consent/ paediatric assent (if applicable) prior to any study specific procedures including medication withdrawal
* Male or Female, ≥12 years of age
* Documented clinical diagnosis of asthma for at least 1 year prior to Visit 2
* Patient must have history of at least 1 asthma exacerbation including one of the following:

  * requiring treatment with systemic corticosteroids
  * an asthma-related hospitalization between 4 weeks and 12 months prior to randomization
* Current Asthma Therapy: Patients must be appropriately using one of the treatments for asthma listed in the protocol combined with achieving certain results when recording an Asthma Control Questionnaire

Exclusion Criteria:

* Patient has a history of life-threatening asthma. Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea requiring non-invasive ventilatory support.
* Patient has required treatment with systemic corticosteroids (tablets, suspensions or injectable) for any reason within 4 weeks prior to Visit 2
* Patient has an ongoing exacerbation, defined as a worsening of asthma that requires treatment with systemic corticosteroids (tablets, suspension, or injectable)
* An asthma exacerbation within 4 weeks of randomization or more than 4 separate exacerbations in the 12 months preceding randomization or more than 2 hospitalizations for treatment of asthma in the 12 months preceding randomization
* Patient has a respiratory infection or other viral/bacterial illness, or is recovering from such an illness at the time of Visit 2 that, in the investigator's opinion, will interfere with the patient's lung function
* Patient must not meet unstable asthma severity criteria as listed in the protocol
* Peak expiratory flow must not be below 50% o predicted normal
* Pregnancy, breast-feeding or planned pregnancy during the study
D: 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

Answer: C