Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double Blind, Double Dummy, Randomised, Multicentre, Two Arm Parallel Group Study to Assess the Efficacy and Safety of FLUTIFORM® pMDI (2 Puffs Bid) vs Seretide® pMDI (2 Puffs Bid) in Subjects Aged ≥12 Years With Moderate to Severe Persistent, Reversible Asthma
Brief Summary: A double blind, double dummy, randomised, multicentre, two arm parallel group study to assess the efficacy and safety of FLUTIFORM® pMDI (2 puffs bid) vs Seretide® pMDI (2 puffs bid) in subjects aged ≥12 years with moderate to severe persistent, reversible asthma.


Options:
A: Inclusion Criteria:

1. Male or female subjects at least aged ≥12 years old.
2. Known history of moderate to severe persistent, reversible asthma for ≥ 6 months prior to the Screening Visit characterized by inadequate asthma control on treatment with an ICS alone OR controlled asthma on treatment with an ICS-LABA combination.
3. Demonstrated a pre-dose FEV1 of ≥ 40% to ≤ 80% for predicted normal values during the Screening Visit (Visit 1) following appropriate withholding of asthma medications (if applicable).

   * No LABA use within 12 hours and/or no SABA use within 6 hours of the PFT.
   * No SAMA (e.g., ipratropium) use within 8 hours and/or no LAMA (e.g., tiotropium) use within 72 hours of the PFT.
   * No use of inhaled ICS-LABA combination asthma therapy within 12 hours of the PFT.
   * Inhaled corticosteroids are allowed on the day of screening.
   * Oral Aminophylline should be withheld for at least 24 hours prior to the PFT.
4. Documented FEV1 reversibility of ≥ 12% (plus ≥ 200ml if the subject is older than 18 years old) within last 12 months which could be accepted by the investigator, or during the screening phase or at Visit 2.
5. Demonstrated satisfactory technique in the use of the study medication.
6. Females of child bearing potential or less than one year post-menopausal must have a negative serum pregnancy test recorded at the screening visit and a negative urine pregnancy test result 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.
7. Willing and able to enter information in the 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, for \<18 years old subjects, both parental consent and subjects assent are needed.

Besides The Inclusion/Exclusion Criteria Checking, Additional Randomisation Criteria Required Following Run-In Period:

1. Demonstrated a pre-dose FEV1 of ≥ 40% to ≤ 80% for predicted normal values at Randomisation Visit (Visit 3) following appropriate withholding of asthma medications (if applicable).
2. ACQ score at Visit 3 ≥ 1.0.
3. Subjects with a good compliance with treatment or patient dairy. The definition of good compliance is that the completeness of diary during the last 14 days of the run-in period is at least 80%. The compliance on diary completeness will be assessed from the aspects below and agreed by the investigator and study Medical Monitor:

   1. Diary info has been filled out on ≥80% of the days during the last 14 days before randomization (e.g., at least 11 days with diary filled completed out of the last 14 days prior to randomization).
   2. 80% main items including the study endpoints related ones have been filled out within the last 14 days prior to randomization.
   3. No other significant incompliance judged by the investigator that indicates the potential future incompliance for critical data collection during the study treatment period.

Exclusion Criteria:

1. The adolescent subjects (age ≥ 12 years to \<18 years) who are on ICS alone at a dose \>250μg bid fluticasone or equivalent OR ICS-LABA combination at a dose of Seretide \> 250/50 μg bid or equivalent.
2. Near fatal or life-threatening (including intubation) asthma within the past year.
3. Chest X-ray at the Investigator's discretion from clinical perspective that reveals evidence of clinically significant abnormalities not believed to be due to asthma.
4. Hospitalization or an emergency visit for asthma within the 4 weeks before the screening visit or during the screening visit.
5. Use of systemic (injectable or oral) corticosteroid medication within 1 month of the Screening Visit.
6. Omalizumab use within the past 6 months prior to the Screening Visit.
7. 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.
8. In the investigator's opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the Screening Visit.
9. Significant, non-reversible, active pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis).
10. 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.) or significant history of exposure to biomass fuel combustion which may be considered a plausible contributory cause to the subject's obstructive lung disease.
11. Current smoking history within 12 months prior to the Screening Visit.
12. Current evidence or known history of alcohol and/or substance abuse within 12 months prior to the Screening Visit.
13. 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.
14. Current use of medications other than those allowed in the protocol that will have an effect on bronchospasm and/or pulmonary function.
15. Current evidence or known history of hypersensitivity or contraindications to the investigational products or components, including the history of paradoxical bronchospasm after inhalation therapy as immediate increase in wheezing and shortness of breath.
16. Subject has received an investigational drug within 30 days of the Screening Visit (12 weeks if an oral or injectable steroid).
17. Subject is currently participating in another clinical study or has already been randomized in this study.
18. Mental incapacity, unwillingness, or language barrier precluding adequate understanding, cooperation or any factors might block patients from protocol defined visits and may impact the patient diary completion at the Investigator's discretion.
B: Inclusion Criteria:

* Ability to confirm voluntary participation and agree to all trial purposes by signing and dating the informed consent forms;
* Participants aged 18 years or more;
* Diagnosis of uncontrolled severe asthma;
* Participants with Forced expiratory volume in 1 second (FEV1) \> 60% of predicted;

Exclusion Criteria:

* Any clinical and laboratory findings that, in the judgment of the investigator, may interfere with the safety of research participants;
* Known hypersensitivity to the formula components used during the clinical trial;
* History of alcohol and/or substance abuse within 12 months prior to Screening Visit.
* Current smoking or smoking history equivalent to "10 pack years"
* Participants with untreated oral candidiasis;
* Pulmonary disease history (e.g., chronic obstructive pulmonary disease \[COPD\], cystic fibrosis, bronchiectasis, tuberculosis);
* Participants with a history of acute asthma exacerbation, respiratory tract infection or hospitalization for asthma in the last 4 weeks;
* Known HIV-positive status or active hepatitis B or C virus test result
* Participants with current evidence or history of uncontrolled coronary artery disease, congestive heart failure, myocardial infarction or cardiac arrhythmia;
* Participants with a current medical history of cancer and/or cancer treatment in the last 5 years;
* Participants using medications that would have an effect on bronchospasm and / or lung function.
C: Key Inclusion criteria

* Male and female adult patients ≥ 18 years old and ≤ 75 years.
* Patients with a documented physician diagnosis of asthma for a period of at least 12 months prior to Visit 1 (Screening).
* Patients who have used ICS and LABA combinations for asthma for at least 3 month and at a stable medium or high dose of ICS for at least 1 month prior to Visit 1 (Screening).
* Pre-bronchodilator FEV1 of \< 80 % of the predicted normal value at screening Visit 1 (spirometry will not be repeated at baseline prior to randomization).
* Patients who demonstrate an increase in FEV1 of ≥ 12 % and 200 mL after administration of 400 µg salbutamol/360 µg albuterol (or equivalent do se) at Visit 1 (Screening). All patients must perform a reversibility test at Visit 1 (Screening). If reversibility is not demonstrated at Visit 1 (Screening), then, reversibility testing may be repeated once during the screening period.
* If reversibility is not demonstrated at Visit 1 (retesting allowed once), patients must be screen failed. Spacer devices are not permitted during reversibility testing Key Exclusion criteria
* Patients who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1
* Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention
* Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Visit 1
* Patients with any chronic conditions affecting the upper respiratory tract
* Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
* Patients with Type I diabetes or uncontrolled Type II diabetes (HbA1c \>9% at screening).
* Patients who have a clinically significant ECG abnormality at Visit 1
* Patients with a history of hypersensitivity or intolerance to any of the study drugs (including excipients)
* Patients with narcolepsy and/or insomnia.
* Patients on Maintenance Immunotherapy (desensitization) for allergies for less than 3 months prior to Visit 2 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 2 but expected to change throughout the course of the study.
* Pregnant or nursing (lactating) women
* Women of child-bearing potential must use Highly effective contraception methods
* Patients who have discontinued LAMA therapy in the past for any safety, tolerability or perceived lack of efficacy reason.
* History of paradoxical bronchospasm in response to inhaled medicines.
* Patients with a history of clinically relevant bronchoconstriction upon repeated forced expiratory maneuvers.
* Patient with a serum potassium level below the laboratory limit of normal at screening.
D: Inclusion Criteria:

* Have a documented history of physician-diagnosed asthma
* Require inhaled asthma maintenance therapy: has been regularly using an ICS/LABA on a stable regimen for at least 4 weeks
* Documented reversibility to albuterol
* A pre-bronchodilator FEV1 \>40% and \<85% of predicted normal value for subjects 18 to 80 years of age or \>40% and \<90% of predicted for subjects 12 to \<18 years of age
* Demonstrate acceptable spirometry performance
* Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol
* Compliance: must be willing to remain at the study center as required per protocol to complete all visit assessments

Exclusion Criteria:

* Oral corticosteroid use (any dose) within 4 weeks
* Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months (including all forms of tobacco, e-cigarettes, and marijuana)
* Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s)
* Completed treatment for lower respiratory infection or asthma exacerbation within 4 weeks
* Hospitalizations for asthma within 3 months
* Historical or current evidence of a clinically significant disease
* Cancer not in complete remission for at least 5 years
* Treatment with investigational study drug (or device) in another clinical study within the last 30 days or 5 half-lives, whichever is longer
* Previously randomized in any PT001 study

Answer: A