Effect of Inhaled Fluticasone Furoate on Short-term Growth in Paediatric Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone furoate; Placebo; Salbutamol
Intervention description: FF will be provided as a dry powder inhaler containing 50 μg of FF as a dry white powder per blister, to be inhaled orally via ELLIPTA.; Placebo will be provided as dry powder inhaler containing placebo as a dry white powder per blister, to be inhaled orally via ELLIPTA.; Salbutamol will be provided as a inhaler.
Intervention MeSH terms: Fluticasone; Xhance; Albuterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 5 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: inhaled corticosteroids; pediatric subjects; asthma; fluticasone furoate

Summary:

      This study will be conducted to evaluate the effect of once daily treatment with fluticasone
      furoate (FF) on lower leg growth in pediatric subjects with persistent asthma by using
      knemometry. Approximately 65 paediatric asthmatic subjects, aged 5 to 11 years (inclusive),
      will be screened to achieve 60 randomised and 50 evaluable subjects. Subjects meeting the
      eligibility criteria will enter the 2 week run-in period. After completing run-in period,
      each subject will be randomly allocated to one of two treatment sequences: inhaled
      fluticasone furoate followed by placebo or placebo followed by inhaled fluticasone furoate.
      Each treatment will be administered via the ELLIPTA™ dry powder inhaler. The two treatment
      periods will be separated by a two-week wash-out period. Subjects completing two treatment
      period will enter into 7 days follow-up period. ARNUITY™ ELLIPTA (FF) is approved in the US
      for adults and adolescents aged 12 and above.

      ARNUITY and ELLIPTA are a registered trademarks of the GlaxoSmithKline group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 5 years to less than 12 years at Visit 1. At least 15 (25%) children of the total
             study population must be aged 5 to less than 8 years.

          -  Male or pre-menarchial female subjects.

          -  Subjects must be pre-adolescent without any signs of puberty (Tanner Stage 1).

          -  Normal range for their height and weight. Weight and height measurements should fall
             within the percentile range 3-97% of normal values for age according to Danish growth
             charts.

          -  Have a documented diagnosis of persistent asthma, as defined by the National
             Institutes of Health for at least 3 months prior to the Screening Visit.

          -  A pre-bronchodilatory forced expiratory flow in 1 second (FEV1) at Visit 1 (Screening)
             >=80% predicted. There should be no Short acting beta-agonist (SABA) use within 4
             hours of this measurement.

          -  Using one of the following asthma therapies prior to entry into the study: SABA
             inhaler alone (e.g. salbutamol) on an as required basis and/or Regular non-inhaled
             corticosteroid (ICS) controller medications for asthma (e.g. cromones or leukotriene
             receptor antagonists) and/or Previously treated with ICS (equipotent to inhaled
             budesonide <=400 micrograms (mcg) total daily dose). There must be no ICS use within 2
             weeks of Visit 1 (Screening).

          -  Able to replace their current SABA treatment with study supplied rescue SABA provided
             at Visit 1 for use as needed for the duration of the study.

          -  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: (1) 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). (2) Subject and their legal
             guardian(s) understand that the study requires them to be treated on an outpatient
             basis. (3) Subject and their legal guardian(s) understand that they must comply with
             study medication and study assessments including recording of peak expiratory flow and
             rescue SABA use, attending scheduled study visits, and being accessible by a telephone
             call.

        Exclusion Criteria:

          -  A history of life-threatening asthma defined for this protocol as an asthma episode
             that required intubation, hypercapnea requiring non-invasive ventilatory support,
             respiratory arrest, hypoxic seizures or asthma-related syncopal episode(s).

          -  Subjects with a history of asthma exacerbation requiring the use of systemic
             corticosteroids (tablets, suspension, or injection) for at least 3 days or a depot
             corticosteroid injection or emergency room attendance (within 3 months) or requiring
             hospitalization for asthma (within 6 months) prior to screening.

          -  Significant, non-reversible active pulmonary disease (e.g. cystic fibrosis,
             bronchiectasis, tuberculosis).

          -  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.

          -  Any fracture in the leg to be measured within 6 months prior to the screening visit.

          -  Any metabolic disorders or other diseases that may impact on normal growth patterns.

          -  No major surgery requiring general anaesthesia for at least 3 months prior to the
             screening visit.

          -  No febrile illnesses with temperature >39 degree celsius for more than five
             consecutive days within the week preceding the Screening Visit.

          -  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 outcome of the study.

          -  Clinical visual evidence of candidiasis at Visit 1 (Screening).

          -  Use of any of the prohibited medications listed in protocol.

          -  Strenuous physical exercise within 3 hours of Visit 1 (Screening)

          -  Drug allergies: Any adverse reaction including immediate or delayed hypersensitivity
             to any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected
             sensitivity to the constituents of the ELLIPTA Inhaler (i.e., lactose, FF).

          -  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.

          -  Unable to use the ELLIPTA inhaler and peak flow meter correctly.

          -  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 (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.