Effect of Fluticasone Furoate Inhalation Powder on the Hypothalamic-pituitary-adrenocortical Axis of Children Aged 5-11 Years With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: FF; Placebo; Montelukast; Albuterol/Salbutamol
Intervention description: FF will be provided as a dry powder inhaler with 30 doses per device, each containing 50 mcg of FF as a dry white powder per blister, to be inhaled orally via ELLIPTA.; Placebo will be provided as dry powder inhaler with 30 doses per device, each containing placebo as a dry white powder per blister, to be inhaled orally via ELLIPTA.; Montelukast will be provided as 4 mg and 5 mg chewable tablets.; Albuterol/Salbutamol will be provided as inhalation aerosol.
Intervention MeSH terms: Albuterol; Montelukast
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 111.0
Sex: All
Minimum age: 5 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: Fluticasone Furoate; Asthma; HPA axis; Children; Inhaled corticosteroid

Summary:

      Inhaled corticosteroids (ICS) have a number of known class effects including
      hypothalamic-pituitary-adrenocortical (HPA) axis suppression. Although the safety of inhaled
      Fluticasone Furoate (FF) on the HPA axis of adults and adolescent asthmatic patients has been
      established, it is important to assess the risk of suppression in children so as to establish
      whether this medicine can be safely used in this young population. This study aims to
      evaluate the effect of inhaled FF on the HPA axis of children 5-11 years of age (inclusive)
      with persistent asthma compared with placebo. Approximately 143 subjects will be enrolled.
      Subjects will enter a 7 to 14 day run-in period on oral montelukast 4 milligrams (mg) (5 year
      old subjects) or 5 mg (6-11 year old subjects) once daily. Eligible subjects will be
      randomized to receive once-daily FF inhalation powder 50 micrograms (mcg) or once-daily
      placebo inhalation powder in the morning via the ELLIPTA™ inhaler for 42 days. Subjects will
      continue to receive open label montelukast during the treatment period. All subjects will be
      provided albuterol/salbutamol inhalation aerosol, to use as needed to treat acute asthma
      symptoms throughout the study.

      ELLIPTA is a registered trademark of the GlaxoSmithKline group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent: Written informed consent from at least one parent/care giver and the
             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)/Institutional
        Review Board (IRB).

        Subject and their legal guardian understands that they must comply with study medication
        and study assessments.

          -  Age: 5-11 years (inclusive) at Visit 1.

          -  Weight: Subjects must weigh at least 17 kilograms (kg).

          -  Gender: Male and pre-menarchial female. Pre-menarchial females are defined as any
             female who has yet to begin menses.

          -  Diagnosis of asthma: Subjects must have a diagnosis of asthma documented in their
             medical history at least 6 months prior to Visit 1.

          -  Childhood Asthma Control Test (C-ACT): Subjects must have a C-ACT score of >19.

          -  Asthma Therapy Prior to Visit 1: Subjects are eligible if they have been using
             non-corticosteroid controller and/or short-acting beta2-agonist (SABA) bronchodilators
             alone for at least 4 weeks prior to Visit 1.

          -  Ability to use Dry Powder Inhalers: Subjects must demonstrate the ability to use the
             ELLIPTA inhaler under the supervision of their parents/caregiver.

          -  SABA: All subjects must be able to replace their current SABA treatment with
             albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed for the duration of
             the study. Albuterol/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.

          -  Peak Flow Meter/Daily Diary Compliance: A subject must be able to use the
             study-provided peak flow meter and the subject/caregiver must be able to maintain the
             electronic diary record.

        Exclusion Criteria:

          -  History of Life-Threatening Asthma: Subjects with 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).

          -  Asthma Exacerbation: 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 (within 3 months) or requiring hospitalization for
             asthma (within 6 months) prior to screening.

          -  Respiratory Infection: 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, expected to affect the subject's asthma status or the subject's ability
             to participate in the study.

          -  Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has
             clinical visual evidence of candidiasis at Visit 1.

          -  Concurrent Disease: Any significant abnormality or medical condition identified at the
             screening medical assessment (including serious psychological disorder and congenital
             metabolic disorders) likely to interfere with the conduct of the study or affect the
             safety of the patient.

          -  Allergies/Intolerance:

        Drug Allergy/Intolerance: Any adverse reaction including immediate or delayed
        hypersensitivity to any Leukotriene receptor antagonist (LTRA), or intranasal, inhaled, or
        systemic corticosteroid therapy. Known or suspected sensitivity/intolerance to the
        constituents of the powder inhaler (i.e. lactose) or montelukast (e.g. phenylalanine).

        Milk Protein Allergy: History of severe milk protein allergy.

          -  Corticosteroid Use:

        Administration of systemic, oral, or depot corticosteroids within 12 weeks of Visit 1 is
        prohibited and during the study.

        Use of an ICS is prohibited during the 8 weeks prior to Visit 1 and during the study.

        Use of intranasal corticosteroids is prohibited during the 4 weeks prior to Visit 1 and
        during the study.

        Use of dermatological/topical corticosteroids during the 8 weeks prior to Visit 1 and
        during the study.

          -  Concomitant Medication: Use of prescription or over-the-counter medications that would
             significantly affect the course of asthma or the HPA axis system of subjects. In
             addition, use of potent cytochrome P450 3A4 (CYP3A4) inhibitors within 4 weeks of
             Visit 1 and during the study (e.g., Clarithromycin, atazanavir, indinavir,
             itraconazole, ketoconazole, nefazadone, nelfinavir; ritonavir; saquinavir;
             telithromycin, troleandomycin, voriconazole, mibefradil, cyclosporine).

          -  Tobacco/Marijuana Use: Present use of any tobacco or marijuana products.

          -  Affiliation with Investigator's Site: 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 employee of the participating investigator.

          -  Parental/ Guardian Factors: Parent or Guardian with 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) and 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.

          -  Clinically significant obesity: Defined as greater than 98th percentile.