Fall Epidemic Viral Pediatric Study
Condition: Asthma
MeSH terms: Asthma
Intervention: FLOVENT™ DISKUS™ 100 mcg BID; ADVAIR™ DISKUS™ 100/50 mcg BID
Intervention description: FLOVENT™ DISKUS™ 100 mcg, one inhalation twice daily (BID) from the DISKUS device from randomization through the end of study (week 16).; ADVAIR™ DISKUS™ 100/50 mcg is a combination product containing a 100 mcg fluticasone propionate and a 50 mcg salmeterol. One inhalation from the DISKUS device twice daily (BID) from randomization through end of study (week 16).
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 339.0
Sex: All
Minimum age: 4 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: pediatric; exacerbation; viral induced exacerbation; asthma

Summary:

      Study ADA113872 is an exploratory 16-week multi-centre, randomized, double-blind, parallel
      group study in pediatric subjects, 4 to 11 years of age, with a history of seasonal asthma
      exacerbation(s). Approximately 40 clinical sites in the United States will randomize 316
      subjects. Eligible subjects will be randomly assigned to one of two double-blind treatments
      using a 1:1 randomization. Subjects will be identified for their eligibility for enrolment
      starting in April 2010. Eligible subjects will be invited to return for randomization into
      the study in August 2010. This exploratory study is being conducted to assess whether
      treatment with ADVAIR™ DISKUS™ 100/50 mcg is more effective at reducing the risk of
      exacerbation and the asthma impairment associated with viral respiratory tract infections
      during the fall season when compared to treatment with FLOVENT™ DISKUS™ 100 mcg.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Outpatient

          -  Subjects must be between the ages of 4 and 11 at Randomization

          -  Subjects must attend day-care, pre-school, elementary school, or middle school.
             Day-care attendance is defined as receiving childcare outside the home for at least 10
             hours per week. Children who are home-schooled are not eligible for this study.
             Children on year round and traditional school calendars are eligible for this study.

          -  Subjects can be randomized into this study at any time between August 2nd, 2010 and
             August 20th, 2010.

          -  Males or pre-menarchal females.

          -  A diagnosis of asthma, as defined by the National Institutes of Health [NIH, 2007]

          -  At Visit 1 subjects must demonstrate a best clinic AM PEF ≥70% of the predicted value
             [Polgar, 1971].

          -  Each subject must have a history of an exacerbation of asthma between September 1st,
             2009 and May 15th, 2010 that required a burst of outpatient systemic corticosteroids
             (oral or parenteral on >1 days for worsening symptoms of asthma) or have had an urgent
             care, hospitalization, or ED visit for asthma during which they received
             oral/parenteral corticosteroids between September 1st, 2009 and May 15th, 2010.

          -  Subjects must have prior or current use of controller ICS medication as listed below:

          -  Subjects who have had prior use of a controller medication consisting of a low dose
             ICS at any time since September 1st, 2009 are eligible for inclusion in this study
             (refer to Table 1 for examples of allowed doses of commonly used ICS).

          -  Subjects currently taking a low dose ICS are eligible for inclusion in the study
             (refer to Table 1 for examples of allowed doses of commonly used ICS).

          -  Subjects' currently taking a moderate dose ICS are eligible for inclusion in the study
             if the subject's asthma has been controlled over the prior 3 months and the subject is
             a candidate for step down therapy, as defined by current asthma management guidelines
             [NIH, 2007].

          -  Subjects' currently taking low dose ICS in combination with a LABA are eligible for
             inclusion in the study if the subject's asthma has been controlled over the prior 3
             months and the subject is a candidate for step down therapy, as defined by current
             asthma management guidelines [NIH, 2007].

          -  All subjects must be able to replace their short-acting beta2-agonists with
             study-issued albuterol inhalation aerosol at Visit 1 for use as needed for the
             duration of the study. If a subject demonstrates the inability to coordinate the use
             of an MDI alone, subjects are permitted to use an Aerochamber Plus spacer. The use or
             non-use of a spacer for albuterol inhalation aerosol should be consistent for each
             subject throughout the study. Subjects must be able to withhold inhaled albuterol for
             at least 6 hours prior to study Visits

          -  Chickenpox: Reported history of clinical varicella or varicella vaccine. If a subject
             needs varicella vaccine this will be arranged with a physician and must be received
             prior to randomization.

          -  Electronic Peak Flow Meter (ePEF)/Electronic Daily Diary (eDiary): A subject must be
             able to use the study-provided electronic peak flow meter and the subject/caregiver
             must be able to enter data using the electronic Diary record.

          -  Responsibilities of Consenting Parent/Legal Guardian: The subject's parent or legal
             guardian must commit to assist the subject at a consistent level with administration
             of investigational product and electronic Diary device and electronic PEF meter
             throughout the study.

          -  A subject must demonstrate adequate and appropriate technique for using the DISKUS™
             device reliably.

          -  Fluency in English or USA Spanish: Subject and/or subject's parent/guardian must be
             able to read, comprehend, and record information in English or USA Spanish.

        Exclusion Criteria:

          -  History of Life Threatening Asthma

          -  Unstable Asthma

          -  Concomitant use of corticosteroid medication

          -  Other Concurrent Diseases/Abnormalities: The known presence of sinus, middle ear,
             oropharyngeal, upper or lower respiratory tract infections within 4 weeks immediately
             preceding randomization that required the use of an antibiotic or was accompanied by
             symptoms of worsening asthma.

          -  Concomitant Medications: Administration of any other prescription or over the counter
             medication which would significantly affect the course of asthma, such as omalizumab
             (Xolair), or interact with sympathomimetic amines, such as: anticonvulsants
             (barbiturates, hydantoins, carbamazepine), polycyclic antidepressants, beta-adrenergic
             blocking agents (both cardio-selective and non-selective), phenothiazines,

          -  Cytochrome P450 3A4 (CYP 3A4) Inhibitors: A subject is not eligible if he/she is
             receiving a strong CYP 3A4 inhibitor within 4 weeks of Visit 1 (e.g., ritonavir,
             ketoconazole, itraconazole).

          -  Immunosuppressive medications: A subject must not be using or require use of
             immunosuppressive medications (e.g. methotrexate, gold, cyclosporine, azathioprine)
             during the study.

        Note: Immunotherapy for the treatment of allergies is allowed during the study provided it
        was initiated 4 weeks prior to Visit 1 and the subject remains in the maintenance phase for
        the duration of the study.

          -  Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia,
             pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia,
             chronic bronchitis, emphysema, cystic fibrosis, dyspnea by any cause other than
             asthma, or other respiratory abnormalities other than asthma.

          -  Other Concurrent Diseases/Abnormalities: Historical or current evidence of clinically
             significant uncontrolled disease that in the opinion of the investigator would put the
             safety of the subject at risk through study participation or would confound the
             interpretation of the results if the condition/disease exacerbated during the study.

        The list of additional excluded conditions/diseases includes, but is not limited to the
        following:

        Uncontrolled hypertension; Uncontrolled hematologic, hepatic, neurologic, or renal disease
        Uncontrolled gastroesophageal reflux disease, Immunologic compromise, Cardiac arrhythmias,
        Tuberculosis (current or untreated), Congestive heart failure, Cushing's disease Coronary
        artery disease, Addison's disease, Current malignancy, Eosinophilic esophagitis
        Uncontrolled diabetes mellitus, Uncontrolled thyroid disorder

          -  Severe Hypersensitivity to Milk Proteins: Any immediate hypersensitivity reaction,
             such as urticaria, angioedema, rash, and bronchospasm to milk proteins

          -  Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to
             any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic
             corticosteroid therapy. Known or suspected sensitivity to the constituents of the Dry
             Powder Inhaler (i.e., lactose).

          -  Tobacco Use: A history of or present use of any tobacco products.

          -  Investigational Medications: A subject must not have participated in a study
             (including a non-interventional study) or used any investigational drug (including
             devices) within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior
             investigational study (whichever is longer of the two).

          -  Child in Care: A Child in Care (CiC) is a child who has been placed under the control
             or protection of an agency, organisation, institution or entity by the courts, the
             government or a government body, acting in accordance with powers conferred on them by
             law or regulation. The definition of a CiC can include a child cared for by foster
             parents or living in a care home or institution, provided that the arrangement falls
             within the definition above. The determination of whether a child meets the definition
             of CiC should be made with the study centre staff in consultation with the responsible
             IRB/Ethics Committee.

          -  Affiliation with Investigator's Site: A subject is an immediate family member of the
             participating investigator, sub investigator, study coordinator, or employee of the
             participating investigator.