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:

* 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
B: Inclusion Criteria:

* Male or female 12 years and above
* Clinical diagnosis of asthma according to the American Thoracic Society definition at least 6 months
* Pre-bronchodilator FEV1 ≥ 45% and ≤ 85% of predicted normal
* Patients with reversible airway obstruction
* Documented daily use of inhaled corticosteroids for ≥ 3 months

Exclusion Criteria:

* History of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures during the 2 years prior to Visit 2
* Hospitalized during previous 6 months for asthma
* Required emergency treatment more than once during previous 6 months for an asthma-related condition
* Intake of oral, rectal or parenteral glucocorticosteroid within 30 days of enrolment
* Respiratory infection affecting the asthma within 30 days
C: Inclusion Criteria:

* A subject must be at least 12 years of age, of either sex, and of any race, with a diagnosis of asthma of at least 12 months duration that is consistent with the following definition:

  * The diagnosis of asthma is based upon clinical history and examination, pulmonary function parameters, and response to beta2-agonists, according to international guidelines.
* A subject must have been using a high dose of inhaled glucocorticosteroid (ICS) either alone or in combination with a long-acting beta2 agonist (LABA) for at least 12 weeks prior to Screening, with no use of oral glucocorticosteroids within 30 days prior to Screening. A subject must have been on a stable asthma regimen (daily dose unchanged) for at least 2 weeks prior to Screening. High daily doses of ICS are defined as follows:

  * \>1000 mcg beclomethasone chlorofluorocarbon (CFC)
  * \>500 mcg beclomethasone hydrofluoroalkane (HFA)
  * \>1000 mcg budesonide dry powder inhaler (DPI)
  * \>2000 mcg flunisolide
  * \>500 mcg fluticasone
  * \>400 mcg MF
  * \>2000 mcg triamcinolone acetonide
  * \>320 mcg ciclesonide

Note: Dose delivery by method or modality other than those noted above must be equivalent.

* A subject must have experienced at least one severe exacerbation requiring a course of oral glucocorticosteroid 2 to 12 months prior to Screening.
* If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, then the subject (and parent/guardian, if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA prior to initiating MF MDI run-in medication.
* To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization, one of the following methods can be used at the Screening Visit, Day-14, or thereafter, but prior to the Baseline Visit:

  * The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within approximately 15 to 20 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg).
  * The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percent of the best and lowest morning pre-bronchodilator PEF over at least 1 week.
  * The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the prebronchodilator (before taking albuterol/salbutamol) morning value and the postbronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value. Note: If a subject is to qualify using diurnal variation, the subject should be instructed to perform his/her PEF evaluation after using his/her bronchodilator in the evening.
* At the Screening Visit, the subject's FEV1 must be \>=50% predicted when all restricted medications have been withheld for the appropriate intervals.
* At the Baseline Visit, the subject's FEV1 must be \>=50% and \<=85% predicted when all restricted medications have been withheld for the appropriate intervals.
* The subject (and parent/guardian for a subject under the age of legal consent) must be willing to give written informed consent and be able to adhere to dose and visit schedules.
* A female subject of childbearing potential must be using a medically acceptable, adequate form of birth control. This includes:

  * hormonal contraceptive as prescribed by a physician (oral combined, hormonal vaginal ring, hormonal implant or depot-injectable);
  * medically prescribed intra-uterine device (IUD);
  * medically prescribed topically-applied transdermal contraceptive patch;
  * condom in combination with a spermicide (double-barrier method);
  * monogamous relationship with a male partner who has had a vasectomy. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A female subject of childbearing potential who is not currently sexually active must agree and consent to using a medically acceptable method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for the open-label MF MDI Run-in Period.

Exclusion Criteria:

* A subject who demonstrates a change (increase or decrease) in absolute FEV1 of \>20% at any time from the Screening Visit up to and including the Baseline Visit. Pulmonary function tests (PFTs) will be performed in the morning.
* A subject who requires the use of \>8 inhalations per day of short-acting beta agonists (SABA) MDI or \>=2 nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit.
* A subject who experiences a decrease in AM or PM peak expiratory flow (PEF) below the Run-in Period stability limit on any 2 consecutive days prior to randomization.
* A subject who experiences a clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication \[including oral or other systemic corticosteroids, but allowing SABAs\]), at any time from the Screening Visit up to and including the Baseline Visit.
* A subject who has been treated in the emergency room (for a severe asthma exacerbation), or admitted to the hospital for management of airway obstruction, within the last 3 months.
* A subject who has ever required ventilator support for respiratory failure secondary to asthma.
* A subject who has experienced an upper or lower respiratory tract infection (viral or bacterial) within the previous 2 weeks prior to Screening and Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution of the event to re-assess eligibility.
* A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history \>10 pack-years.
* A subject with a clinically significant abnormal vital sign.
* A subject with evidence (upon visual inspection, laboratory culture is not required) of clinically significant oropharyngeal candidiasis at Baseline (Visit 3) with or without treatment. If there is evidence of oropharyngeal candidiasis at Screening or Pre-Baseline Visit, the subject may be treated as appropriate and the Baseline Visit can be scheduled upon resolution. If there is evidence of oropharyngeal candidiasis at the Baseline Visit, the subject may be treated as appropriate and the visit can be rescheduled upon resolution.
* A subject with a history of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, could interfere with the study, or require treatment that might interfere with the study. Specific examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta blockers, active hepatitis, coronary artery disease, arrhythmia, stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts, acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as clinically diagnosed chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, etc. Other conditions that are well-controlled and stable (eg, hypertension not requiring beta blockers) will not prohibit participation if deemed appropriate per the investigator's judgment.
* A subject who is known to be allergic to or intolerant of ICS, beta2 agonists, or any of the excipients present in the medications used in this study.
* A female subject who is breast-feeding, pregnant, or intends to become pregnant while participating in this study.
* A subject who is a known illicit drug user.
* A subject who is known to be human immunodeficiency virus (HIV) positive (HIV testing will not be conducted in this study).
* A subject who is unable to correctly use an oral MDI inhaler.
* A subject who has been taking any of the restricted medications prior to Screening without meeting the required washout timeframes.
* A subject who cannot adhere to the permitted concomitant medications and prohibited medications.
* A subject participating in this study may not participate in this same study at another investigational site. In addition, a subject cannot participate in a different investigational study at any site, during the same timeframe of this study.
* A subject must not be randomized into this study more than once.
* No person directly associated with the administration of the study may participate as a study subject. No family member of the investigational study staff may participate in this study.
* A subject who previously participated in a trial with MF/F.
* Subjects with a history of significant QTC prolongation (ie, QTc\>500 msec) are excluded from participation in the study.
D: Ages eligible for study: 12 years and above; genders eligible for study: both; prior steroid use: steroid-requiring or steroid-free.

Inclusion Criteria:

* History of asthma for at least 12 months.
* For steroid-requiring patients, documented use of inhaled corticosteroid for at least 4 weeks prior to Screening Visit
* For steroid-free patients, no history of inhaled steroid asthma medication for at least 12 weeks prior to Screening Visit.
* Demonstrate FEV-1 of 60-85% of predicted normal values at Screening and Baseline Visit.
* Documented reversibility of 15% within 12 months of Screening or at Screening Visit (15% increase from pre-FEV-1 levels following albuterol inhalation or nebulized albuterol administration).
* Symptoms of Asthma during Run-in
* Females of childbearing potential must have a negative urine pregnancy test at Screening and Baseline Visits. Females are eligible only if they are not pregnant or lactating, and are either sterile, or using acceptable methods of contraception.
* Must otherwise be healthy.
* Provide written informed consent. Wishes of minors must be respected.

Exclusion Criteria:

* Life-threatening asthma within past year or during Run-In Period.
* History of systemic corticosteroid medication within 3 months before Screening Visit.
* History of omalizumab use within past 6 months.
* History of leukotriene receptor antagonist use, e.g. montelukast, within past week.
* Current evidence or history of any clinically significant disease or abnormality including uncontrolled hypertension, uncontrolled coronary artery disease, congestive heart failure, myocardial infarction, or cardiac dysrhythmia.
* Upper or lower respiratory infection within 4 weeks prior to Screening Visit or during Run-In Period.
* Significant, non-reversible, pulmonary disease (e.g., chronic obstructive pulmonary disease \[COPD\], cystic fibrosis, bronchiectasis).
* Known Human Immunodeficiency Virus (HIV)-positive status.
* Smoking history equivalent to "10 pack years".
* Current smoking history within 12 months prior to Screening Visit.
* Current evidence or history of alcohol and/or substance abuse within 12 months prior to Screening Visit.
* Patients who are confined in institution

Answer: A