Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 6-month, Open Label, Randomised, Efficacy Study to Evaluate Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) Inhalation Powder Delivered Once Daily Via the Dry Powder Inhaler ELLIPTA™ Compared With Usual ICS/LABA Maintenance Therapy Delivered by Dry Powder Inhaler in Subjects With Persistent Asthma
Brief Summary: The combination of FF, an ICS and VI, an orally inhaled LABA has been developed as a once-daily combination therapy for the long-term maintenance treatment of asthma in adults and children \>=12 years of age. Pivotal phase III studies have demonstrated the safety and efficacy of FF/VI in asthma. However, it is increasingly acknowledged that randomised clinical trials tend to be highly controlled and enrol a more highly selected subject population than is expected to be prescribed the medication post-approval. There is a need for data in a more representative population in close to a 'real life' conditions, where physicians have the ability to choose the best treatment in their view for any individual subject and adapt treatments to subjects' characteristics and response. This multi-center, open-label, randomized, parallel group study will evaluate the efficacy and safety of FF/VI compared with two usual ICS/LABA fixed combination (fluticasone propionate/salmeterol \[FP/S\] or budesonide/formoterol \[BUD/F\]) in subjects with persistent asthma, in a "close to real life" settings. FF/VI will be administered once-daily (QD) via ELLIPTA dry powder inhaler (DPI) and FP/S or BUD/F will be administered twice daily (BID) via DISKUS™ and TURBUHALER™ DPI respectively. ELLIPTA is a new powder inhaler designed to be easy to use. The total duration of subject participation will be approximately 6 months (24 weeks). ELLIPTA and DISKUS are registered trademarks of the GSK group of companies. TURBUHALER is a registered trademark of AstraZeneca.


Options:
A: Inclusion Criteria:

* Informed consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
* Gender and Age: Male or female subjects aged \>=18 and \<=75years of age at Screening visit.

Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:

Non-reproductive potential defined as: Pre-menopausal females with one of the following - Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause \[refer to laboratory reference ranges for confirmatory levels\]); Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until Week 24.

GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP:

This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including a \<1percent rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1 percent rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

* Type of subject: Subjects with documented physician's diagnosis of asthma \>=1 year, unsatisfactorily controlled asthma (ACT \<20 at Screening and Randomisation visit) treated by ICS alone and intended to be treated by ICS/LABA maintenance therapy; France Only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a Social Security category.
* Current Asthma Therapy: All subjects must be prescribed maintenance therapy and receiving ICS alone without LABA for at least 4 weeks prior to Randomisation visit; Other background asthma medication such as anti-leukotrienes or theophylline is permitted as an alternative to ICS alone, if initiated at least 4 weeks prior to screening visit.
* Subject questionnaires Subjects must be able to complete the questionnaires themselves.

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 within the last 6 months before Screening and Randomisation visit.
* Subjects having a severe and unstable asthma, with ACT score \< 15 at Visit 1 and at Visit 2, and/or a history of repeated severe exacerbations (3/year) and/or a severe exacerbation in the previous 6 weeks before Visit 1 and Visit 2.
* Chronic obstructive pulmonary disease (COPD) Respiratory Disease: A subject must not have current evidence or diagnosis of chronic obstructive pulmonary disease at Screening visit.
* Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at screening \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\].
* Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease at Screening and Randomisation visit. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
* Subjects with a history of adverse reaction including immediate or delayed hypersensitivity to any intranasal, inhaled, or systemic corticosteroid and LABA therapy and to components of the inhalation powder (e.g., lactose, magnesium stearate) at Screening and Randomisation visit. In addition, subjects with a history of severe milk protein allergy that, in the opinion of the Investigator, contraindicates the subject's participation will also be excluded.
* Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Randomisation visit or within five half-lives (t½) of the prior investigational study (whichever is longer of the two), (if unsure discuss with the medical monitor prior to screening).
* Chronic user of systemic corticosteroids: A subject who, in the opinion of the Investigator, is considered to be a chronic user of systemic corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening) at Screening visit.
* Subjects treated by the monoclonal antibody omalizumab or mepolizumab at Visit 1. Treatment with omalizumab or mepolizumab is not allowed during the study.
* Subjects involved in other clinical trials at Screening visit.
* Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
* Subjects who plan to move away from the geographical area where the study is being conducted during the study.
B: Inclusion Criteria:

* History of asthma ≥ 1 year and diagnosed before 40 years old
* Uncontrolled asthma with double therapy only on medium doses of Inhaled CorticoSteroid (ICS) in combination with Long-acting beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5
* Pre-bronchodilator FEV1 \<80% of the predicted normal value
* Positive reversibility test
* At least 1 documented asthma exacerbation in the previous year

Exclusion Criteria:

* Pregnant or lactating women
* Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
* Patients with any asthma exacerbation or respiratory tract infection in the 4 weeks prior screening
* Current or ex-smokers (\>= 10 packs year)
* Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening
C: 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
D: 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.

Answer: A