This is a Phase III, multicenter, randomized, double-blind, stratified, parallel-group study with three active comparators in subjects with moderate to severe persistent asthma. The study consists of a run-in period of 4 weeks, followed by a treatment period of 12 weeks, and a follow up contact period of one week. The total duration of the study is 17 weeks. 990 subjects will be randomized to one of three treatments (FF/VI Inhalation Powder 200/25 mcg once daily in the evening; FF/VI Inhalation Powder 100/25 mcg once daily in the evening; FF 100 Inhalation Powder once daily in the evening) for 12 weeks. In addition, all subjects will be supplied albuterol/salbutamol inhalation aerosol at Visit 1 to use as needed for acute asthma symptoms throughout the entire study. Subjects will attend four on-treatment visits at Weeks 2, 4, 8, and 12 (Visits 4 through 7).

Inclusion Criteria:

• Subjects must give their signed and dated (written) informed consent to participate. Written informed consent must be obtained if a subject's current medication is changed as a result of study participation
• Outpatient >=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health. Countries with local restrictions prohibiting enrolment of adolescents will only enroll subjects >=18 years of age
• Male or an eligible female. Eligible female is defined as having non-childbearing potential or having childbearing potential and using an acceptable method of birth control consistently and correctly.
• Best pre-bronchodilator FEV1 of 40% to 80% of their predicted normal value.
• Demonstrate >=12% and >=200 mL reversibility of FEV1 within 10 to 40 minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (or an equivalent nebulized treatment with albuterol/salbutamol solution) or have documented reversibility testing within the 6 months prior to Visit 1 meeting this measure of reversibility. A spacer device may be used for testing, if required.
• If subject have received ICS for at least 12 weeks prior to Visit 1 and their treatment during the 4 weeks immediately prior to Visit 1 consisted of either of the two regimens (a or b).a.) A stable mid-dose or high-dose of ICS alone (e.g., >=FP 250 mcg twice daily) or b.) A stable dose of a mid-dose ICS/LABA combination (e.g., FP/Salmeterol [SALM] 250/50 mcg twice daily) or an equivalent combination via separate inhalers.
• Use of ICS/LABA are not permitted with LABA on the day of Visit 1.
• Must be able to replace current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, during the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits

Exclusion Criteria:

• History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
• Upper or lower respiratory tract, sinus, or middle ear that is: not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the investigator, expected to affect the subject's asthma status or the subject's ability to participate in the study.
• Any asthma exacerbation that required oral corticosteroids within the 12 weeks prior to Visit 1 or, resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
• A subject must not have current evidence of atelectasis (segmental or larger), bronchopulmonary dysplasia, chronic obstructive pulmonary disease, Or any evidence of concurrent respiratory disease other than asthma
• A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
• Chronic stable hepatitis B or C are acceptable provided their screening alanine transaminase (ALT) is <2x upper limit of normal (ULN) and the y otherwise meet the entry criteria. Chronic co-infection with both hepatitis B and hepatitis C are not eligible
• Clinical visual evidence of candidiasis at Visit 1
• Use of any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½), whichever is longer of the two.
• Allergies to drug or milk protein: any adverse reaction, to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or known or suspected sensitivity to the constituents of the NDPI, or history of severe milk protein allergy
• Administration of medication that would significantly affect the course of asthma, or interact with study drug
• Use of immunosuppressive medications during the study.
• Use of potent CYP3A4 inhibitor within 4 weeks of Visit 1.
• A subject or his/her parent or legal guardian has any infirmity, disability, disease, or resides in a geographical location which seems likely, in the opinion of the Investigator, to impair compliance with any aspect of this study protocol, including visit schedule, and completion of the daily diaries.
• Current smoker or has a smoking history of 10 pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, or pipe tobacco).
• If subject is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
• Subject previously randomized to treatment with FF/VI or FF in another Phase III study
• Subjects working on night shift a week prior to Visit 1 or during the study period.
• Adolescents who are wards of the state or government

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.