Effects of a Orally Inhaled Fluticasone Furoate on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma Over a Year
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone furoate; Placebo; Montelukast; Short Acting Beta 2 Agonist
Intervention description: Fluticasone furoate will be supplied as 50 mcg per blister dry white powder for inhalation using ELLIPTA inhaler.; Placebo will be supplied as dry white powder Lactose for inhalation using ELLIPTA inhaler.; Montelukast will be supplied as 4 mg chewable tablet (5 year old subjects) and as 5 mg chewable tablet (>=6 year old subjects); Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.
Intervention MeSH terms: Fluticasone; Xhance; Montelukast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 477.0
Sex: All
Minimum age: 5 Years
Maximum age: 9 Years
Healthy volunteers: No
Keywords: Growth Velocity; Prepubertal; Asthma; Paediatric

Summary:

      There is a regulatory requirement to evaluate the extent of reduction (if any) of growth
      velocity associated with inhaled corticosteroid (ICS) containing products that are to be
      administered to children, and to this end there is Food and Drug Administration (FDA)
      regulatory guidance. This is a randomised, single-blind (run-in period)/double-blind
      (treatment period), parallel group, placebo controlled, multicentre study to assess the
      effect of once daily (OD) inhaled fluticasone furoate (FF) 50 microgram (mcg) on growth
      velocity in prepubertal asthmatic children on a background therapy of open-label montelukast.
      This study will be conducted over a total duration of approximately 76 weeks: 16-week run-in
      period (single-blind placebo inhaler), 52-week double-blind treatment period (inhaled FF 50
      mcg /placebo administered OD in the morning for 52 weeks) and 8-week follow-up period. The
      purpose of the study is to evaluate the magnitude of effect (with a level of precision) on
      growth velocity of prepubertal asthmatic paediatric subjects (aged 5 to <9 years) following
      administration of OD inhaled FF 50 mcg for one year. This study fulfills European Union (EU)
      and United States (US) regulatory requirements for the evaluation of potential growth
      suppression in children.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects.

          -  Age: Males between 5 and <9 years old; Females between 5 and <8 years old.

          -  Subjects must be pre-pubertal (Tanner Stage 1).

          -  Height centile between 3% and 97% based on local growth charts.

          -  Subjects with body weight and body mass index that is between 3rd and 97th centile
             based on the United State (US) Centres for Disease Control and Prevention (CDC)
             standard statistics or any local standards outside the US.

          -  A documented history of symptoms consistent with a diagnosis of asthma for at least 6
             months prior to Visit 1.

          -  A pre-bronchodilatory forced expiratory flow in 1 second (FEV1) at Visit 1 (Screening)
             of between >=60% to <=95% predicted. There should be no short acting beta 2 agonist
             (SABA) use within 4 hours of this measurement.

          -  Able to replace their current SABA treatment with study supplied rescue
             albuterol/salbutamol provided at Visit 1 for use as needed for the duration of the
             study.

          -  A childhood asthma control test (cACT) score of >19.

          -  Subjects should have required at least one course of corticosteroid for their asthma
             (inhaled or oral) in the past year.

          -  There must be no ICS use within 6 weeks of Visit 1 (Screening).

          -  There must be no oral corticosteroids use within 12 weeks of Visit 1 (Screening).

          -  Using one or more of the following asthma therapies prior to entry into the study:

        Short acting beta-agonist (SABA) inhaler alone (example given [e.g.] salbutamol) on an as
        needed basis and/or regular non-ICS controller medications for asthma (e.g. cromones or
        leukotriene receptor antagonists).

        - Written informed consent from at least one 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 local requirement. The study investigator is
        accountable for determining a child's capacity to assent for 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 they must comply with
        study medication administration regimens and study assessments including recording of
        symptom scores and rescue albuterol/salbutamol use, attending all study visits, and being
        accessible by telephone.

        Exclusion Criteria:

          -  Growth Criteria: Any previous or current condition that affects growth, including
             sleep disorders, endocrine disorders, skeletal dysplasia, Turner and Noonan syndromes,
             Marfan, Beckwith-Wiedeman and Sotos syndromes, Klinefelter's syndrome, coeliac
             disease, inflammatory bowel diseases and renal failure or any significant abnormality
             or medical condition that is identified at the screening medical assessment (including
             serious psychological disorder) that is likely to interfere with the conduct of the
             study.

          -  Subjects with premature adrenarche.

          -  A child who is unable to stand, or who finds standing difficult due to illness or
             physical disabilities should be excluded.

          -  Disease Criteria: Subjects with a history of asthma exacerbation requiring the use of
             systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or
             use of a depot corticosteroid injection within 3 months or those requiring
             hospitalisation for asthma (within 6 months) prior to screening.

          -  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.

          -  Clinical visual evidence of candidiasis at Visit 1 (Screening).

          -  Any significant abnormality or medical condition identified at the screening medical
             assessment that in the Investigator's opinion, preclude entry into the study due to
             risk to the subject or that may interfere with the outcome of the study.

          -  General: Prior use of any medication or treatment that might affect growth including,
             but not limited to: amphetamines, anticonvulsants, biphosphonates, calcitonin,
             calcitriol, erythropoietin, growth hormone, methylphenidate, phosphate binders,
             antithyroid drugs (e.g., Methimazole) or thyroid hormone.

          -  Use of any of the prohibited medications listed in the study protocol.

          -  Hypersensitivity: Known hypersensitivity to corticosteroids, leukotrienes, or any
             excipients in the ELLIPTA (ELLIPTA is a Glaxosmithkline owned trademark for dry powder
             inhaler) inhaler and study tablets.

          -  Milk Protein Allergy: History of severe milk protein allergy.

          -  The subject has 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, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than 4 investigational medicinal products within 12 months prior to
             the first dosing day.

          -  Children who are 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 known or suspected psychiatric disease,
             intellectual deficiency, substance abuse or other condition (e.g. 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 (e.g. 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.