Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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/Adolescent (> 12 Yrs) Hispanic Subjects With Asthma
Brief Summary: The purpose of this study is to determine the effectiveness and safety of SYMBICORT® pMDI (a medication approved by the Food and Drug Administration(FDA)) in the Hispanic population.


Options:
A: Inclusion criteria:

1. Male or female subjects at least 18 years old.
2. Females less than one year post-menopausal must have a negative urine pregnancy test recorded at the screening visit prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner.
3. Known history of severe persistent, reversible asthma for ≥ 6 months prior to the Screening Visit characterised by treatment with ICS at a dose of ≥ 500µg fluticasone or equivalent.
4. Demonstrated a FEV1 of ≥ 40% to ≤ 80% for predicted normal values (Quanjer et al., 1993) during the Screening Visit (Visit 1) and Randomisation Visit (Visit 3) following appropriate withholding of asthma medications (if applicable).

   * No β2-agonist use on day of screening.
   * No use of inhaled combination asthma therapy on day of screening.
   * Inhaled corticosteroids are allowed on day of screening.
5. Documented reversibility of ≥ 15% in FEV1 in the screening phase.
6. Demonstrated satisfactory technique in the use of the study medication.
7. Willing and able to enter information in the electronic diary and attend all study visits.
8. Willing and able to substitute study medication for their pre study prescribed asthma medication for the duration of the study.
9. Written informed consent obtained.

   Inclusion criteria required following run-in:
10. Subject has used rescue medication for at least 3 days AND had at least one night with sleep disturbance (i.e., sleep disturbance score of ≥ 1) OR at least 3 days with asthma symptoms (i.e., a symptom score of ≥ 1) during the last 7 days of the run-in period.

Exclusion criteria:

1. Near fatal or life-threatening (including intubation) asthma within the past year.
2. Hospitalisation or an emergency visit for asthma within the 4 weeks before the screening visit.
3. Known history of systemic (injectable or oral) corticosteroid medication within 1 month of the Screening Visit.
4. Known history of omalizumab use within the past 6 months.
5. Current evidence or known history of any clinically significant disease or abnormality including uncontrolled coronary artery disease, congestive heart failure, myocardial infarction, or cardiac dysrhythmia. 'Clinically significant' is defined as any disease that, in the opinion of the Investigator, would put the subject at risk through study participation, or which would affect the outcome of the study.
6. In the investigator's opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the Screening Visit.
7. Significant, non-reversible, active pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis).
8. Known Human Immunodeficiency Virus (HIV)-positive status.
9. Subject has a smoking history equivalent to "10 pack years" (i.e., at least 1 pack of 20 cigarettes /day for 10 years or 10 packs/day for 1 year, etc.).
10. Current smoking history within 12 months prior to the Screening Visit.
11. Current evidence or known history of alcohol and/or substance abuse within 12 months prior to the Screening Visit.
12. Subject has taken B-blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole (Hismanal), quinidine type antiarrhythmics, or potent CYP 3A4 inhibitors such as ketoconazole within the past week.
13. Current use of medications other than those allowed in the protocol that will have an effect on bronchospasm and/or pulmonary function.
14. Current evidence or known history of hypersensitivity or idiosyncratic reaction to test medications or components.
15. Subject has recieved an investigational drug within 30 days of the Screening Visit (12 weeks if an oral or injectable steroid).
16. Subject is currently participating in a clinical study.
B: Adult and adolescent subjects of either sex and any race, at least 12 years of age or older, with a diagnosis of asthma of at least 12 months' duration, will be eligible for enrollment. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to receive treatment assignment.

Key Inclusion Criteria Include

- A subject must have been using a medium daily dose of inhaled glucocorticosteroid (ICS) (either alone or in combination with a long-acting beta agonist (LABA)) for at least 12 weeks and must have been on a stable regimen (daily dose unchanged) for at least 2 weeks prior to Screening. Medium daily doses of ICS are defined as follows:

* \>500 to 1000 mcg beclomethasone chlorofluorocarbon (CFC)
* \>250 to 500 mcg beclomethasone hydrofluoroalkane (HFA)
* \>600 to 1000 mcg budesonide dry powder inhaler (DPI)
* \>1000 to 2000 mcg flunisolide
* \>250 to 500 mcg fluticasone
* 400 mcg MF
* \>1000 to 2000 mcg triamcinolone acetonide

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

* 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 combination at the Screening Visit, and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 to 3 weeks prior to the Baseline/Randomization Visit.
* 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:

  1. The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within 15 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg) or of nebulized SABA (2.5 mg) if confirmed as standard office practice, OR
  2. The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the highest and lowest morning prebronchodilator PEF over at least 1 week, OR
  3. The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the prebronchodilator morning value and the postbronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value.
* At the Screening Visit, the subject's FEV1 must be ≥60% and ≤90% predicted.
* At the Baseline Visit, the subject's FEV1 must be ≥60% and ≤85% predicted when all restricted medications have been withheld for the appropriate intervals.
* Clinical laboratory tests (complete blood counts \[CBC\], blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor. An electrocardiogram (ECG) using a centralized trans-telephonic technology at the Screening Visit must be clinically acceptable to the investigator. A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.
* A female subject of childbearing potential must have been using a medically acceptable, adequate form of birth control. This includes: 1) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant); 2) medically prescribed intra-uterine device (IUD); 3) condom in combination with a spermicide (double barrier method); 4) 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 birth control 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 enrollment.

Key Exclusion Criteria Include

* 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.
* A subject who requires the use of greater than eight inhalations per day of SABA MDI, or two or more 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 PEF below the Screening Period stability limit on any 2 consecutive days prior to Randomization.
* A subject who experiences an occurrence of any clinical deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) as judged by the clinical investigator at any time from the Screening Visit up to and including the Baseline Visit.
* 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
C: Inclusion Criteria:

* Male or Female, Hispanic (self-reported), \> 12 years of age
* Moderate to severe asthma requiring treatment with an inhaled corticosteroid
* Diagnosis of asthma for at least 6 months

Exclusion Criteria:

* Subjects requiring treatment with systemic corticosteroids (e.g., oral, parenteral, ocular)
* Any significant disease or disorder that may jeopardize a subject's safety
D: Inclusion Criteria:

* Diagnosis of asthma
* Baseline lung function tests as determined by protocol.
* Required and received treatment with inhaled corticosteroids and/or lung treatments specified in the protocol within timeframe and doses specified in protocol.

Exclusion Criteria:

* Severe asthma
* Has required treatment with any non-inhaled corticosteroid within previous 4 weeks, has sensitivity to drugs specified in the protocol or requires treatment with beta-blockers
* Had cancer within previous 5 years or currently has any other significant disease or disorder as judged by the investigator

Answer: C