Safety and Efficacy Study of Fluticasone Furoate/Vilanterol (FF/VI) Fixed Dose Combination (FDC) Compared to FF Alone in Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: FF/VI via ELLIPTA DPI; FF via ELLIPTA DPI
Intervention description: ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).; ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized to receive FDC of FF/VI inhalation powder compared to FF inhalation powder, once daily in cohort A and cohort B.
Masking: Double (Participant, Investigator)
Masking description: This will be a double blind study. Subjects and investigator will be masked.
Enrollment: 906.0
Sex: All
Minimum age: 5 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Fluticasone furoate; Efficacy; Vilanterol; Asthma; Safety; GW642444; GW685698

Summary:

      The goal of asthma treatment is to achieve and maintain asthma control and to reduce the
      future risk of exacerbations. Inhaled corticosteroids (ICS) are considered as the most
      effective anti- inflammatory treatment for all severities of persistent asthma. For children
      >=5 years of age and adolescents whose asthma is uncontrolled, low-dose ICS plus adjunctive
      therapy with long-acting beta agonist (LABA) is considered as effective. Thus, this study is
      designed to evaluate the efficacy and safety of FF (ICS component)/VI (LABA component)
      compared to FF alone for the treatment of asthma, in subjects aged 5 to 17 years old
      currently uncontrolled on ICS. The study will be conducted over a total duration of
      approximately 29 weeks: 4 week run-in period, 24-week double-blind treatment period and
      1-week follow-up period. Subjects will be randomized to receive FDC of FF/VI or FF
      administered via ELLIPTA® dry powder inhaler (DPI). The dose of both FF/VI and FF alone will
      be selected based on the age of subjects. Subjects will receive a short acting beta 2 agonist
      (SABA) (albuterol /salbutamol) as a rescue medication throughout the study. A total of 870
      subjects will be randomized in the study. Of this, 652 subjects will be aged 5 to 11 years
      (cohort A), and 218 will be aged 12 to 17 years inclusive (cohort B). ELLIPTA is a registered
      trademark of GlaxoSmithKline (GSK) group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  For all subjects: Between 5 and 17 years of age inclusive, at the time of signing the
             informed consent.

          -  A history of symptoms consistent with a diagnosis of asthma for at least 6 months.

          -  Pre-bronchodilator FEV1 >50 percent to <=90 percent predicted normal. A minimum of 2
             efforts that are considered acceptable (not necessarily repeatable) are required to be
             eligible.

          -  Lung function reversibility defined as an increase of >=12 percent in FEV1 within 10
             to 40 minutes following 2 to 4 inhalations of salbutamol inhalation aerosol (or 1
             nebulized treatment with albuterol/salbutamol solution). Use of a spacer is permitted.

          -  Uncontrolled asthma, with a childhood asthma control test (cACT)/ACT score <=19.

          -  Receiving stable asthma therapy (SABA inhaler plus ICS [total daily dose <=FP 250
             micrograms (mcg) or equivalent]) for at least 4 weeks prior to Visit 1 (i.e.
             screening).

          -  Able to replace their current SABA treatment with salbutamol aerosol inhaler at Visit
             1 for use as needed for the duration of the study. Salbutamol metered dose inhaler
             (MDI) will be administered with or without a spacer, to be used as determined by the
             investigator. The use or non-use of the spacer should be consistent for an individual
             subject throughout the study.

          -  Male or female subjects will be included. Females of reproductive potential must agree
             to follow 1 of the options listed (which include abstinence) in the Modified List of
             Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential
             (FRP) from 30 days prior to the first dose of study medication and until at least five
             terminal half-lives or until any continuing pharmacologic effect has ended, whichever
             is longer after the last dose of study medication and completion of the follow-up
             call. The investigator is responsible for ensuring that subjects understand how to
             properly use these methods of contraception.

          -  Written informed consent from at least 1 parent/care giver (legal guardian) and
             accompanying informed assent from the subject (where the subject is able to provide
             assent) prior to admission to the study. If applicable, subject must be able and
             willing to give assent to take part in the study according to the local requirement.
             The study investigator is accountable for determining a child's capacity to assent to
             participation in a research study, taking into consideration any standards set by the
             responsible independent ethics committee (IEC); subject and their legal guardian(s)
             understand that the study requires them to be treated on an outpatient basis; subject
             and their legal guardian(s) understand that they must comply with study medication and
             study assessments including recording of PEF and rescue SABA use, attending scheduled
             study visits, and being accessible by a telephone call.

          -  For subjects eligible for randomization; asthma control: uncontrolled asthma, with a
             cACT/ACT score <=19.

          -  A technically acceptable pre-bronchodilator FEV1 >50 percent to <=90 percent predicted
             normal at Visit 2. A minimum of 2 efforts that are considered acceptable and
             repeatable following the over read are required to be eligible.

          -  Symptoms and rescue use: demonstrated and reported in a daily diary symptoms of asthma
             (a score of >=1 on the day-time or night-time asthma symptom scores) and/or daily
             albuterol/salbutamol on at least 3 of the last 7 consecutive days of the run-in period
             (not including the date of randomization).

          -  Compliance with run-in medication: compliance is defined as use of run-in medication
             on at least 4 of the last 7 consecutive days of the run-in period (not including the
             date of randomization) recorded in the electronic subject diary.

          -  Compliance with completion of the daily diary reporting: defined as completion of all
             questions on 4 out of the last 7 days during the run-in period (not including the date
             of randomization).

        Exclusion Criteria:

          -  For all subjects: History of life threatening asthma defined as an asthma episode that
             required intubation and/or was associated with hypercapnea, respiratory arrest or
             hypoxic seizures.

          -  Any asthma exacerbation requiring the use of oral steroids within 6 weeks of Visit 1,
             systemic or depot corticosteroids within 12 weeks of Visit 1, or ER attendance within
             3 months of Visit 1 or hospitalization within 6 months of Visit 1.

          -  A culture documented or suspected bacterial or viral infection of the upper or lower
             respiratory tract, sinus or middle ear that has not resolved within 4 weeks of Visit 1
             and which 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.

          -  Clinical visual evidence of oropharyngeal candidiasis.

          -  Fasting blood glucose at screening >100 milligrams/deciliter (mg/dL) (5.6 moles per
             liter [mol/L]).

          -  Obesity (Body Mass Index [BMI] above the 97th centile based on the centers for disease
             control and prevention [CDC] charts).

          -  Any significant abnormality or medical condition identified at the screening medical
             assessment (including serious psychological disorder) that in the investigator's
             opinion, preclude entry into the study due to risk to the subject or that may
             interfere with the conduct and/or outcome of the study.

          -  QTc >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block or
             any other clinically significant abnormality in the screening 12-lead ECG.

          -  Use of any prohibited medications.

          -  Present use of any tobacco products.

          -  Drug allergies: any adverse reaction including immediate or delayed hypersensitivity
             to any beta 2-agonists, sympathomimetic drug or any intranasal, inhaled, or systemic
             corticosteroid therapy. Known or suspected sensitivity to the constituents of the
             ELLIPTA Inhaler (i.e. lactose or magnesium stearate).

          -  Milk Protein Allergy: history of severe milk protein allergy.

          -  Participated in a clinical trial and has received an investigational product within
             the following time period prior to the first dosing day in the current study: 30 days,
             five half-lives or twice the duration of the biological effect of the study treatment
             (whichever is longer).

          -  Exposure to more than 4 investigational medicinal products within 12 months prior to
             the first dosing day.

          -  An affiliation with the investigator site: the parents/guardians or child is an
             immediate family member of the participating investigator, sub-investigator, study
             coordinator, or employee of the participating investigator.

          -  The parent or guardian has a history of psychiatric disease, intellectual deficiency,
             substance abuse or other condition (example, inability to read, comprehend or write)
             which may affect: validity of consent to participate in the study; adequate
             supervision of the subject during the study; compliance of subject with study
             medication and study procedures (example, completion of daily diary, attending
             scheduled clinic visits); subject safety and well-being.

          -  Children in care: children who are wards of the government or state are not eligible
             for participation in this study.

          -  For subjects eligible for randomization; Changes in asthma medication that occur after
             screening.

          -  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.

          -  Evidence of an exacerbation, defined as a: deterioration of asthma requiring the use
             of oral corticosteroids for at least 3 days, or a depot corticosteroid injection, or
             an in-patient hospitalization due to asthma that required systemic corticosteroids
             between screening and randomization.

          -  Clinical visual evidence of oropharyngeal candidiasis at the randomization Visit.

          -  Unable to use the ELLIPTA inhaler correctly.