Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-blind, Active Controlled, Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination FF/UMEC/VI With the Fixed Dose Dual Combination of FF/VI, Administered Once-daily Via a Dry Powder Inhaler in Subjects With Inadequately Controlled Asthma
Brief Summary: A once-daily 'closed' triple FDC therapy of FF/UMEC/VI via a single ELLIPTA® dry powder inhaler (DPI) is being developed by GlaxoSmithKline (GSK) with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This is a phase III, multi-center, active-controlled, double-blind, parallel-group study to compare the efficacy, safety and tolerability of the FDC of FF/UMEC/VI with the FDC of FF/VI. This study has 5 phases: Pre-Screening (Visit 0), Screening/Run-in, Enrolment/Stabilization, Randomization/Treatment, and Follow up. At Visit 1 (Screening), subjects meeting all protocol defined inclusion/exclusion criteria will enter a 3-week run-in period and will receive fixed dose inhaled corticosteroid/long-acting beta agonist (ICS/LABA) (fluticasone/salmeterol, 250/50 micrograms (mcg), via the DISKUS® DPI) one inhalation twice a day. At Visit 2 (Enrolment), eligible subjects will be enrolled into the 2-week stabilization period to receive FF/VI (100/25 mcg via the ELLIPTA DPI once a day, in the morning). At the conclusion of the stabilization period (Visit 3), all subjects who meet the pre-defined randomization criteria will be randomized 1:1:1:1:1:1 during the treatment period to receive either FF/UMEC/VI (100/62.5/25 mcg; 200/62.5/25 mcg; 100/31.25/25 mcg; 200/31.25/25 mcg) or FF/VI (100/25 mcg; 200/25 mcg) via the ELLIPTA DPI once daily in the morning. The duration of the treatment period is variable but will be a minimum of 24 weeks and a maximum of 52 weeks. Subjects will have up to 6 on-treatment clinic visits scheduled at Visits 3, 4, 5, 6, 7 and 8/End of Study (EOS) (Weeks 0, 4, 12, 24, 36 and 52, respectively). A follow-up visit will be conducted approximately 7 days after the end of treatment period or, if applicable, after the early withdrawal visit. Subjects will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Approximately 2250 subjects will be randomized, with approximately 375 subjects randomized to each of the 6 double-blind treatment arms to ensure approximately 337 evaluable subjects per treatment arm. DISKUS and ELLIPTA are registered trademarks of GSK groups of companies.


Options:
A: Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

* Type of Subject: Outpatient
* Age: 12 years of age or older at Visit 1. For sites in the following countries, subjects recruited will be ≥18 years of age: Bulgaria, Czech Republic, Germany, Greece, Lithuania, New Zealand, Russian Federation, Turkey and any other countries where local regulations or the regulatory status of study medication permit enrollment of adults only.
* Gender: Male or Eligible Female
* To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:
* Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
* Implants of levonorgestrel
* Injectable progestogen
* Oral contraceptive (either combined estrogen/progestin or progestin only)
* Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
* Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of six days).
* Double barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm).
* NB: For German sites, female subjects must use a method of birth control other than the double barrier method.
* The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds)
* Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required of all females. This test will be performed at the initial screening visit (Visit 1) and Visit 8. In addition, a urine pregnancy test will be performed on the evening of the double-blind treatment visit, prior to randomization (Visit 3) and at Visits 4 through 7.
* Asthma Diagnosis: Asthma as defined by the National Institutes of Health \[National Institutes of Health, 2007\].
* Severity of Disease: A best FEV1 of 40%-85% of the predicted normal value during the morning Visit 1 screening period or a best FEV1 of 40%-90% of the predicted normal value during the evening Visit 1 screening period.
* Reversibility of Disease: Demonstrated a ≥ 12% and ≥200mL reversibility of FEV1 within approximately 30-minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (spacers are permitted for reversibility testing if required) or one nebulized albuterol/salbutamol solution at the screening period. Re-screening of subjects during the Visit 1 screening period: If a subject does not meet the inclusion criteria based upon FEV1 percent predicted and/or reversibility, the subject may return to the site once within 4 days and repeat the lung function tests.
* Current Anti-Asthma Therapy: Subjects must have been using a non-corticosteroid controller or short acting beta2-agonist bronchodilators alone (with no inhaled corticosteroids use for at least 6 weeks) for ≥ 3 months preceding Visit 1.
* Short- Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. The use of spacer devices with metered dose inhaler (MDI) or nebulized albuterol/salbutamol will not be allowed during the study with the exception of their use during reversibility testing at Visit 1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to all study visits.
* Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
* Compliance: Subjects must be able to comply with completion of the Daily Diary (includes paper medical conditions diary).
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Inclusion Criteria for Randomization

At the end of the run-in period, a subject will be eligible to enter the treatment period of the study if he/she meets the following criteria at Visit 3:

* Evening pre-dose percent predicted FEV1 of between 40% and 90% of their predicted normal.
* Any combination of the daily asthma symptom scores (day-time plus night-time) of ≥1 or albuterol/salbutamol use on at least 4 of the last 7 consecutive days of the run-in period (immediately preceding Visit 3).

Exclusion Criteria:

* History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
* Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks before Visit 1 and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.
* Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1. A subject must not have had any hospitalization for asthma within 6 months prior to Visit 1.
* Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, hepatic disease, renal disease, hematological disease, neurological disease, or pulmonary disease (including, but not confined to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease). 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. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, clinically significant coronary heart disease, stroke within 3 months of Visit 1, poorly controlled peptic ulcer, immunologic compromise, tuberculosis (current or untreated), Addison's disease, uncontrolled thyroid disorder, known aortic aneurysm, clinically significant cardiac arrhythmia, uncontrolled hypertension1, hematological, hepatic, or renal disease, current malignancy2, cushings disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse.
* systolic blood pressure ≥160, or diastolic blood pressure \>100
* history of malignancy is acceptable only if subject has been in remission for one year prior to Visit 1 (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to Visit 1)
* Patients with a history of tuberculosis who have received an approved prophylactic treatment regimen or an approved active treatment regimen and who have had no evidence of active disease for a minimum of 2 years may be enrolled \[American Thoracic Society, 2003; American Thoracic Society, 2005\]"
* Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of oral candidiasis at Visit 1.
* Investigational Medications: A subject must not have participated in a study or used any investigational drug within 30 days prior to Visit 1.
* Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the novel dry powder inhaler or DISKUS/ACCUHALER (i.e., lactose or magnesium stearate).
* Milk Protein Allergy: History of severe milk protein allergy.
* Immunosuppressive Medications: A subject must not be using, or require use, of immunosuppressive medications during the study.

NOTE: Immunotherapy for the treatment of allergies is allowed during the study provided that the treatment was initiated prior to Visit 1 and the subject is maintained on a stable regimen throughout the study period.

* Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and non-compliant with study medication or procedures (e.g. completion of daily diary). Neurological or psychiatric disease or history of drug or alcohol abuse which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirements excludes study participation.
* Tobacco Use : Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco).
* Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.
* Corticosteroid Use: Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.

Administration of inhaled corticosteroids within 6 weeks of Visit 1.

* Potent Cytochrome P450 3A4 (CYP3A4) inhibitors: Patients who are receiving potent CYP3A4 inhibitors within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).

Exclusion Criteria for Randomization At the end of the run-in period, a subject will not be eligible to enter the treatment period of the study if they meet any of the following criteria.

* Clinical Laboratory Abnormalities: Clinically significant abnormal laboratory tests during Visit 1 which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality. When in doubt, GlaxoSmithKline, or designee, should be notified so that a joint decision can be made.
* Changes in asthma medication (excluding albuterol/salbutamol inhalation aerosol provided at Visit 1).
* Occurrence of an culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Asthma exacerbation, defined as any worsening of asthma requiring any treatment other than rescue albuterol/salbutamol or regular inhaled corticosteroid use. This includes requiring the use of systemic corticosteroids and / or emergency room visit or hospitalization or a change in subject's regular inhaled corticosteroid dose.
* A subject will not be eligible for randomization if he/she has an abnormal visual oropharyngeal exam at the randomization Visit 3 (visual clinical evidence of oral candidiasis).
* Non-compliance with completion of the Daily Diary, defined as: - Completion of AM and PM symptom scores on less than 4 days out of the last 7 days immediately preceding Visit 3.
* Completion of AM and PM rescue use on less than 4 days out of the last 7 days immediately preceding Visit 3.
* Completion of AM and PM PEF measurements on less than 4 days out of the last 7 days immediately preceding Visit 3.
* Recording run-in asthma medication use on less than 4 days out of the last 7 days immediately preceding Visit 3.
B: Inclusion Criteria for Screening

* Age: 18 years of age or older at the time of signing the informed consent.
* Diagnosis: Subjects with a diagnosis of asthma as defined by the National Institutes of Health at least one year prior to Visit 0.
* Symptomatic: Subjects with inadequately controlled asthma (ACQ-6 score \>=1.5) despite ICS/LABA maintenance therapy at Visit 1.
* Asthma Control: In the 1 year prior to Visit 1

  * A documented healthcare contact for acute asthma symptoms or
  * A documented temporary change in asthma therapy for acute asthma symptoms, according to a pre-specified asthma action plan (or equivalent)
* Current Asthma Maintenance Therapy: Subjects are eligible if they have required daily ICS/LABA for at least 12 weeks prior to Visit 0 with no changes to maintenance asthma medications during the 6 weeks immediately prior to Visit 0 (including no changes to a stable total dose of ICS of \>250 mcg/day fluticasone proprionate \[FP, or equivalent\]).
* Spirometry: A best pre-bronchodilator morning (ante meridian \[AM\]) FEV1 \>=30% and \<85% of the predicted normal value at Visit 1. Predicted values will be based upon the European Respiratory Society (ERS) Global Lung Function Initiative.
* Reversibility of Disease: airway reversibility defined as \>=12% and \>=200 milliliter (mL) increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1.
* If the subject does not meet the above reversibility criteria at Visit 1 then the reversibility assessment may be repeated once within 7 days of Visit 1 if either criteria a) or b) are met: a) \>=9% increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1. b) Documented evidence of a reversibility assessment within 1 year prior to Visit 1 which demonstrated a post-bronchodilator increase in FEV1 of \>=12% and \>=200 mL.

Should the subject successfully demonstrate airway reversibility (defined as \>=12% and \>=200 mL increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol) at the second attempt then, provided that all other eligibility criteria assessed at Visit 1 are met, the subject may enter the 3-week run-in period.

* Short-Acting beta2 Agonists (SABAs): All subjects must be able to replace their current SABA inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Subjects must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to study visits.
* Male or eligible Female, defined as having documentation of non-reproductive potential or reproductive potential as follows:

A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, is not planning on becoming pregnant during the study and at least one of the following conditions applies: Non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, \>45 years, in the absence of hormone replacement therapy). In questionable cases for women \<60 years of age, a blood sample with simultaneous follicle stimulating hormone and estradiol falling into the central laboratory's postmenopausal reference range is confirmatory. Females under 60 years of age, who are on hormone replacement therapy (HRT) and whose menopausal status is in doubt, are required to use a highly effective method to avoid pregnancy 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. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, subjects can resume use of HRT during the study without use of a highly effective method to avoid pregnancy; Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from the screening visit until after the last dose of study medication and completion of the follow-up visit. The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

* Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form and in this protocol. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.

Exclusion Criteria for Screening

* Pneumonia: Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1.
* Asthma Exacerbation: Any asthma exacerbation requiring a change in maintenance asthma therapy in the 6 weeks prior to Visit 1. Note: Subjects requiring a temporary change in asthma therapy (e.g., oral corticosteroids or increased dose of ICS) to treat an exacerbation in the 6 weeks prior to Visit 1 are not explicitly excluded at Visit 1 provided that, at the Investigator's discretion, the subject's condition is stable after they have resumed their pre-exacerbation maintenance asthma therapy (without modification) and they are considered appropriate for enrolment into this study of up to 12 month's duration.
* Chronic Obstructive Pulmonary Disease: Subjects with the diagnosis of chronic obstructive pulmonary disease, as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, including history of exposure to risk factors (i.e., especially tobacco smoke, occupational dusts and chemicals, smoke from home cooking and heating fuels) and a post-albuterol/salbutamol FEV1/Forced Vital Capacity (FVC) ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of =\<70% of predicted normal values and onset of disease \>=40 years of age.
* Concurrent respiratory disorders: Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases or abnormalities other than asthma.
* Risk Factors for Pneumonia: Immune suppression (e.g., human immunodeficiency virus, Lupus) or other risk factors for pneumonia (e.g., neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis).
* Patients at potentially high risk (e.g., very low body mass index (BMI), severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.
* Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. 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.
* Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Note: Chronic stable hepatitis B and C are acceptable if the subject otherwise meets entry criteria.
* Clinically significant Electrocardiogram abnormality: Evidence of a clinically significant abnormality in the 12-lead ECG performed during screening. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following: Atrial fibrillation (AF) with rapid ventricular rate \>120 Beats Per Minute (BPM); sustained or non-sustained ventricular tachycardia (VT); Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted); QT interval corrected for heart rate by Fridericia's formula (QTcF) \>=500 milliseconds (msec) in subjects with QRS \<120 msec and QTcF \>=530 msec in subjects with QRS \>=120 msec.
* Unstable or life threatening cardiac disease: Subjects with any of the following at Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.
* Antimuscarinic effects: Subjects with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.
* Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the subject has been considered cured by treatment.
* Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
* Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.
* Tobacco Use: Subjects who are: Current smokers (defined as subjects who have used inhaled tobacco products within the 12 months prior to Visit 1 \[i.e., cigarettes, e-cigarettes/vaping, cigars or pipe tobacco\]) or former smokers with a smoking history of \>=10 pack years (e.g., \>=20 cigarettes/day for 10 years).
* Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
* Allergy or Hypersensitivity: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate.
* Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
* Affiliation with Investigator site: Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.
* Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials.

Inclusion Criteria for Enrolment

* Inadequately controlled asthma: Subjects with inadequately controlled asthma (ACQ-6 score \>=1.5) at Visit 2.
* Percent-predicted FEV1: A best pre-bronchodilator morning (AM) FEV1 \>=30% and \<90% of the predicted normal value at Visit 2. Predicted values will be based upon the ERS Global Lung Function Initiative
* Liver function tests at Visit 1: alanine aminotransferase (ALT) \<2 x upper limit of normal (ULN); alkaline phosphatase \<=1.5xULN; bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* Compliance with completion of the Daily eDiary reporting defined as completion of all questions/assessments on \>=4 of the last 7 days during the run-in period.

Exclusion Criteria for Enrolment

* Respiratory Infection: Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Severe asthma exacerbation: Evidence of a severe exacerbation during screening or the run-in period, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
* Asthma medication: Changes in asthma medication (excluding run-in medication and albuterol/salbutamol inhalation aerosol provided at Visit 1).
* Laboratory test abnormalities: Evidence of clinically significant abnormal laboratory tests during screening or run-in which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality.

Inclusion Criteria for Randomization

* Compliance with completion of the Daily eDiary reporting defined as completion of all questions/assessments on \>=4 of the last 7 days during the stabilization period.

Exclusion Criteria for Randomization

* Respiratory Infection: Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the stabilization period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Severe asthma exacerbation: Evidence of a severe exacerbation during enrolment or the stabilization period, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
* Asthma medication: Changes in asthma medication (excluding stabilization period medication provided at Visit 2 and albuterol/salbutamol inhalation aerosol provided at Visit 1).
C: Inclusion criteria:

* Type of Subject: Outpatient
* Age: 12 years of age or older at Visit 1 (or ³18 years of age or older if local regulations or the regulatory status of study medication permit enrollment of adults only).
* Gender: Male or eligible female - Females are eligible to participate only if they are currently non-pregnant and non-lactating. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following: Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject, Implants of levonorgestrel, Injectable progestogen, Oral contraceptive (either combined estrogen/progestin or progestin only), Any intrauterine device (IUD) with a documented failure rate of less than 1% per year, Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm), The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds), Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days),
* Asthma Diagnosis: Asthma as defined by the National Institutes of Health \[National Institutes of Health, 2002; GINA, 2005\].
* Severity of Disease: A best AM FEV1 of 50% to 80% of the predicted value during Visit 1 based on the "Standardization of Lung Function Tests" \[European Respiratory Society, 1993\] standards for 18 years and older or Polgar \[Polgar, 1971\] standards for 12 to 17 years and race adjusted for African-Americans \[American Thoracic Society, 1991\].
* Reversibility of Disease: Demonstrated ³12% and 200mL reversibility of FEV1 within 30 minutes following 200 to 400mcg of albuterol/salbutamol inhalation aerosol (or one nebulized albuterol/salbutamol treatment) at Visit 1. If a subject fails to demonstrate an increase in FEV1 of ³12% and 200mL, the subject is not eligible for the study and will not be allowed to re-screen.
* Concurrent Anti-Asthma Therapy: Subjects must be using an inhaled corticosteroid for at least 3 months prior to Visit 1 and be maintained on a stable dose for four weeks prior to Visit 1 at one of the following doses: Anti-Asthma Therapy Maximum Daily Dose (mcg/day) Fluticasone propionate MDI CFC/HFA ≤220mcg1/≥250mcg2 Fluticasone propionate DPI 200mcg Beclomethasone dipropionate 420mcg1/500mcg2 Beclomethasone dipropionate HFA 160mcg1/200mcg2 Budesonide DPI 400mcg Flunisolide 1000mcg Triamcinolone acetonide 1000mcg Mometasone furoate 200mcg Ciclesonide 160mcg1/200mcg2

  1. Ex-actuator dose: dose delivered to the lungs
  2. Ex-valve dose: dose expressed from the valve
* Short-Acting Beta2-Agonist: All subjects must be able to replace short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as-needed for the duration of the study. Subjects must be able to withhold all inhaled short-acting beta-sympathomimetic bronchodilators for at least 6 hours prior to study visits.Note: Nebulized albuterol/salbutamol will not be allowed during the study with the exception of its use during reversibility testing at Visit 1. The use of albuterol/salbutamol through the DISKUS/ACCUHALER device will not be allowed during the study.
* Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
* Compliance: Subjects must be able to comply with all the study requirements.

Exclusion criteria:

* History of Life-Threatening Asthma: History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
* Anti-Asthma Medications: Asthma medications listed below must not have been used prior to Visit 1 for the required interval listed below, and not taken during the study: Within 24 hours of Visit 1: Oral short-acting beta2-agonists: Within 2 weeks of Visit 1:Combination therapy containing inhaled beta2-agonists and ICS for asthma (e.g., fluticasone propionate/salmeterol combination, budesonide/formoterol combination);Slow-release bronchodilators (e.g., aminophylline, theophylline);Anticholinergics; Long-acting beta2-agonists (e.g., salmeterol); Ketotifen; Nedocromil sodium; Sodium cromoglycate; Oral long-acting beta2-agonists. Within 4 weeks of Visit 1: Anti-leukotrienes including suppressors of leukotriene production and antagonists. Within 12 weeks of Visit 1: Systemic, oral, parenteral, or depot corticosteroids; Anti-IgE (e.g., omalizumab).
* Other Medications: The medications listed below must not have been used prior to Visit 1 for the required interval indicated below, and not taken during the study: Within 4 weeks of Visit 1: Known potent inhibitors of CYP3A4 (e.g., ritonavir, ketoconazole)
* Respiratory Infection: History of a respiratory tract infection within 4 weeks of Visit 1. In addition, the subject must be excluded, if such infection occurs between Visits 1 and 2.
* Asthma Exacerbation: History of a an asthma exacerbation within 4 weeks of Visit 1, any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1, or any hospitalization due to asthma exacerbation within 6 months of Visit 1.
* Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior investigational study (which ever is longer of the two) or concurrently during the study.
* Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, or pulmonary disease (including, but not confined to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease). 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.
* Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has evidence of oropharyngeal candidiasis at Visit 1.
* Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy.
* Milk Protein Allergy: History of severe milk protein allergy.
* Immunosuppressive Medications: A subject must not be using, or require use of, immunosuppressive medications during the study.

Note: Immunotherapy for the treatment of allergies is allowed during the study provided that it was initiated prior to Visit 1 and the subject is maintained on a stable daily dose throughout the study period.

* Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and compliance with study medication or procedures (e.g., completion of daily diary). Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject's proper completion of the protocol requirements excludes study participation.
* Tobacco Use: A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco) and must not have historical use of \>10 pack years (e.g., 20 cigarettes/day for 10 years).
* Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
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: B