The Efficacy of Fluticasone Furoate/Vilanterol Versus (vs) Fluticasone Furoate on Asthma
The Efficacy of Fluticasone Furoate/Vilanterol Versus (vs) Fluticasone Furoate on Asthma
The objective of this study is to evaluate fluticasone furoate/vilanterol compared with
 fluticasone furoate alone in subjects with asthma that is uncontrolled on low to mid dose
 inhaled corticosteroid (ICS) or low dose ICS/ long acting beta agonist (LABA) combination.
 This is a phase IV, randomized, double-blind, parallel group, multicenter study evaluating
 fluticasone furoate/vilanterol 100/25 micrograms (mcg) and fluticasone furoate 100 mcg once
 daily, delivered as an inhalation powder using the ELLIPTA® device in subjects with
 uncontrolled asthma despite daily ICS or ICS/LABA therapy. The study will measure treatment
 response and asthma control using the Asthma Control Questionnaire-7 (ACQ-7) focusing on
 symptomatic control. In this study, proportion of subjects with an improvement in ACQ-7 score
 of >=0.5 at Week 12 compared to Baseline for the fluticasone furoate/vilanterol 100 mcg/25
 mcg and fluticasone furoate100 mcg groups will be assessed. The total study duration for each
 subject will be 17 weeks including 4-week run in period, 12-week treatment period and 1-week
 follow up period. Approximately 1012 subjects will be randomized into the study. ELLIPTA is a
 registered trademark of GlaxoSmithKline group of companies.
Screening Inclusion Criteria

 -  Capable of giving signed informed consent.

 -  Male or female subjects aged >= 18 years of age at Screening (Visit 1). A female
 subject is eligible to participate if she is not pregnant not breastfeeding, and at
 least one of the following conditions applies; Not a woman of childbearing potential
 (WOCBP); A WOCBP who agrees to follow the contraceptive guidance during the treatment
 period and for the duration of the study.

 -  A diagnosis of persistent asthma for at least 12 weeks prior to Screening (Visit 1).

 -  All subjects must be using an ICS with or without LABA for at least 12 Weeks prior to
 Visit 1. Two populations are eligible for enrolment: Subjects maintained on a stable
 ICS low to medium-dose fluticasone propionate 100 to 250 mcg twice daily or equivalent
 for at least 4 weeks prior to Visit 1; Subjects maintained on a stable dose of an
 ICS/LABA low-dose combination product (e.g., SERETIDE/ADVAIR 100/50 mcg twice daily or
 equivalent, via other combination products or via separate inhalers) for at least 4
 weeks prior to Visit 1.

 -  Subjects must have a best pre-bronchodilator FEV1 of 50% - 80% of their predicted
 normal value. Predicted values will be based upon Global Lung Function Initiative
 (GLI) equations for spirometry reference values.

 -  Subjects must demonstrate >=12% and 200 milliliter 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) at Visit 1.
 Subjects that have documented reversibility meeting the criteria above within the last
 6 months prior to Visit 1 (Screening) will be eligible and do not need to repeat the
 reversibility assessment at Visit 1 (Screening). Reversibility measurements, including
 historical reversibility, should follow/meet the recommendations of the American
 Thoracic Society (ATS)/ European Respiratory Society (ERS) Task force: Standardization
 of Lung Function Testing.

 -  All subjects must be able to replace their current short-acting bronchodilator (SABA),
 or other reliever strategy, with albuterol/salbutamol at Visit 1 (Screening), to be
 used only on an as-needed basis for the duration of the study. Each subject must be
 judged capable of withholding albuterol/salbutamol for at least 6 hours prior to
 performing spirometric evaluations.

 -  Subjects must be able to read and complete the questionnaire and electronic daily
 diary themselves.

 Screening Exclusion Criteria

 -  Defined for this protocol as an asthma episode that required intubation and/or was
 associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5
 years.

 -  An asthma exacerbation requiring systemic corticosteroids within 12 weeks prior to
 Visit 1. Any exacerbation requiring overnight hospitalization requiring additional
 treatment for asthma within 6 months prior to Visit 1.

 -  Current tobacco smoker or has a smoking history of >=10 pack-years (20 cigarettes/day
 for 10 years).

 -  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 of Visit 1
 and 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.

 -  Women who are pregnant or lactating or are planning on becoming pregnant during the
 study.

 -  A subject must not have current evidence of: Atelectasis - segmental or larger;
 Bronchopulmonary dysplasia; Chronic bronchitis; Chronic obstructive pulmonary disease
 (COPD) current or past diagnosis including asthma/COPD overlap; Pneumonia;
 Pneumothorax; Interstitial lung 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
 participant at risk through study participation or would confound the interpretation
 of the efficacy results if the condition/disease exacerbated during the study.

 -  A subject must not have used any investigational drug within 30 days prior to Visit 1
 or within five half-lives (t1/2) of the prior investigational study, whichever is
 longer of the two periods.

 -  Any adverse reaction including immediate or delayed hypersensitivity to any
 beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic
 corticosteroid therapy, or excipients used with fluticasone furoate/vilanterol 100/25
 or fluticasone furoate 100 (i.e., drug, lactose or magnesium stearate).

 -  History of severe milk protein allergy.

 -  Administration of prescription or non-prescription medication that would significantly
 affect the course of asthma, or interact with study treatment.

 -  A subject must not be using or require the use of immunosuppressive medications during
 the study.

 -  A subject will not be eligible if he/she has any infirmity, disability, disease, or
 geographical location which seems likely (in the opinion of the investigator) to
 impair compliance with any aspect of this study protocol.

 -  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 an employee
 of the participating investigator.

 Randomisation Inclusion Criteria

 -  Uncontrolled asthma (ACQ-7 >=1.5 at Visit 2).

 -  Demonstrated and reported in a daily diary on >=4 of the last 7 consecutive days of
 the run-in period (not including the date of randomisation): a score of >=1 on the
 day-time symptom scores and/or; a score of >=1 on the night-time asthma symptom scores
 and/or; albuterol/salbutamol use.

 -  Compliance is defined as completion of all questions/assessments, both morning and
 evening, on >=4 of the last 7 days during the run-in period. This does not include the
 items collected for the Asthma Daily Symptom Diary (ADSD).

 -  Compliance is defined as use of run-in medication on >=4 of the last 7 consecutive
 days of the run-in period (not including the date of randomisation) recorded in the
 electronic subject diary.

 Randomisation Exclusion Criteria

 -  Positive urine pregnancy test at Visit 2.

 -  Use of any prohibited medications during the run-in period or at Visit 2.

 -  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 subjects asthma status or the participant's ability to
 participate in the study.

 -  Evidence of a severe exacerbation, defined as deterioration of asthma requiring the
 use of systemic corticosteroids (tablets, suspension, or injection) for at least 3
 days or an in-subject hospitalization or emergency department (ED) visit due to asthma
 that required systemic corticosteroids between Visits 1 and 2.