Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerability, PK and PD Study
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone Furoate; Fluticasone Furoate/Vilanterol
Intervention description: 100mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.; 100/25 mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 5 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: pediatric ages 5 to 11 years

Summary:

      This study will investigate the safety and tolerability, pharmacokinetics, and
      pharmacodynamics of fluticasone furoate/vilanterol (FF/VI) 100/25mcg administered using the
      novel dry powder inhaler in children aged 5 to 11 years with persistent asthma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy as determined by a study physician, based medical history, physical
             examination, laboratory testing, and electrocardiogram (ECG); with no significant
             medical condition apart from asthma, eczema, or rhinitis. A subject with a clinical
             abnormality or laboratory parameters outside the reference range for this study may be
             included if the Investigator and GSK Medical Monitor agree the finding is unlikely to
             introduce additional risk factors or interfere with the study procedures.

          -  Male and pre-menarchial female subjects aged 5 to less than 12 years on the last
             planned treatment day are eligible for this study. Pre-menarchial females are defined
             as any female who has not begun menses and is considered Tanner Stage 2 or less.

          -  Diagnosis of asthma at least 6 months prior to screening.

          -  Stable asthma therapy (fluticasone propionate, total daily dose less than or equal to
             400 microgram or equivalent) and short acting beta-agonist (SABA) inhaler for at least
             4 weeks prior to screening.

          -  Subjects must be controlled on their existing asthma treatment at screening, which
             will be continued during the run-in, washout and run-out periods (but not during
             active treatment periods). Control is defined as a Childhood Asthma Control Test score
             of >19 and (Peak Expiratory Flow) PEF more than 75 percent predicted.

          -  Subjects must demonstrate an ability to accept and effectively use a demonstration
             inhaler from the demonstration kits provided.

          -  Subjects must weigh at least 20 kilograms.

          -  The subject and parent/guardian are able to understand and comply with protocol
             requirements, instructions, and protocol stated restrictions. The parent or guardian
             must have the ability to read, write, and record diary information collected
             throughout the study. The parent or guardian must have the ability to manage study
             drug administration and PEF assessments.

          -  At least one parent/guardian has signed and dated the written informed consent prior
             to admission to the study. This will be accompanied by informed assent from the
             subject for children aged 7 to 11 years.

        Exclusion Criteria:

          -  Subjects with a history of life-threatening asthma, an asthma exacerbation requiring
             systemic corticosteroids or Emergency Room attendance (within 3 months) or requiring
             hospitalization (within 6 months) prior to screening.

          -  Subjects with any medical condition or circumstance making the volunteer unsuitable
             for participation in the study.

          -  Culture-documented or suspected bacterial or viral infection of the upper or lower
             respiratory tract, sinus, or middle ear, not resolved within 4 weeks of screening
             leading to a change in asthma management; or, in the opinion of the investigator, is
             likely to affect the subject's asthma status or ability to participate in the study.

          -  Clinical visual evidence of oral candidiasis at screening.

          -  Subjects currently receiving (or have received within 4 weeks of screening) asthma
             therapies including theophyllines, long-acting inhaled beta-agonists, oral
             beta-agonists, or who have changed their asthma medication within 4 weeks of
             screening.

          -  Significant abnormality of rate, interval, conduction or rhythm in the 12-lead ECG
             (electrocardiogram), determined by the investigator in conjunction with the age and
             gender of the child and the assessment provided by the remote analysis service.

          -  QTcF (QT interval corrected for heart rate using Fridericia's formula) more than 450
             milliseconds or an ECG not suitable for QT measurement (e.g. poorly defined
             termination of the T wave).

          -  Aspartarte aminotransferase, Alanine aminotransferase, alkaline phosphatase and
             bilirubin more than 1.5 times Upper Limit of Normal (ULN) (isolated bilirubin more
             than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin
             less than 35 percent).

          -  A known or suspected sensitivity to any constituents of the novel dry powder inhaler
             (i.e. lactose or magnesium stearate) (e.g. history of severe milk protein allergy)

          -  Any adverse reaction including immediate or delayed hypersensitivity to any
             beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic
             corticosteroid therapy.

          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
             supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is
             longer) prior to the first dose of study medication, unless in the opinion of the
             Investigator and GSK Medical Monitor the medication will not interfere with the study
             procedures or compromise subject safety.

          -  Consumption of red wine, seville oranges, grapefruit or grapefruit juice, and/or
             pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
             to the first dose of study medication.

          -  The subject has participated in a clinical trial and has received an investigational
             product within 30 days, 5 half-lives, or twice the duration of the biological effect
             of the investigational product (whichever is longer).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of the lesser of 50 millilitres (mL) or 3mL per kilogram within a 56 day
             period.

          -  Parent/guardian has a history of psychiatric disease, intellectual deficiency,
             substance abuse, or other condition (e.g. inability to read, comprehend and write)
             which will limit the validity of consent to participate in this study.

          -  Unwillingness or inability of the subject or parent/guardian to follow the procedures
             outlined in the protocol.

          -  Subject who is mentally or legally incapacitated.

          -  Children who are wards of the state or government.

          -  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.