Crossover Study Comparing Fluticasone Furoate (FF)/Vilanterol (VI) Once Daily Versus Fluticasone Propionate (FP) Twice Daily in Subjects With Asthma and Exercise-Induced Bronchoconstriction (EIB)
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone furoate/ Vilanterol 100 mcg/25 mcg; Fluticasone propionate 250 mcg; Placebo via ELLIPTA inhaler; Placebo via DISKUS / ACCUHALER
Intervention description: FF/VI 100/25 mcg will be administered via ELLIPTA inhaler once daily in the evening; FP 250mcg will be administered via DISKUS inhaler, twice daily, once in the morning and once in the evening; Placebo will be administered via ELLIPTA inhaler once daily in the evening; Placebo will be administered via DISKUS / ACCUHALER, twice daily, once in the morning and once in the evening
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 75.0
Sex: All
Minimum age: 12 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Fluticasone furoate; activity monitoring; Vilanterol; Cross-over; exercise-induced bronchoconstriction; exercise challenge; double-dummy; asthma; spirometry; fluticasone propionate

Summary:

      This is a multicenter, randomized, double-blind, double-dummy, crossover study with two
      2-week treatment periods separated by a 2-week wash-out period. Subjects will participate in
      up to eight study visits and have a follow up phone call approximately a week after the last
      clinic visit. Visits 1, 2, 3, 5 and 6 are evening visits that will be conducted between 5PM
      and 11PM. Visit 4 and Visit 7 are also evening visits that will begin between 5PM and 11PM
      and continue over a period of approximately 24 hours. Subjects will be required to attend
      three clinic visits during this 24-hour period. An exercise challenge (using a treadmill)
      will be conducted at Visit 2, Visit 3 and Visit 6 (after 23 hours of the first treatment dose
      in each Treatment Period); and at 12 and 23 hours post evening dose at Visits 4 and 7.
      Spirometry will be conducted at specified visits and prior to and after each exercise
      challenge.

      Subjects with symptomatic allergic rhinitis at Visit 1 (screening) may be treated for up to
      four weeks with intranasal corticosteroids followed by a repeat screening visit to determine
      eligibility prior to entry into the study.

      Eligible subjects at visit 1 will complete a 4-week single blind run-in on FP 250 microgram
      (mcg) twice daily (BID), followed by 2-week double-blind Treatment Period 1 on randomized
      treatment, a 2-week single blind washout period on FP 250 mcg BID, 2-week double-blind
      Treatment Period 2 receiving the alternative treatment, and follow-up contact approximately
      7-days after completing Treatment Period 2. The total duration of study participation is
      approximately 11 weeks; and up to 15 weeks for subjects with Symptomatic Allergic Rhinitis.

      The primary objective of the study is to evaluate the protective effect of fluticasone
      furoate/vilanterol (FF/VI) 100/25 mcg once-daily compared with fluticasone propionate (FP)
      250 mcg twice-daily against exercise-induced bronchoconstriction in adolescent and adult
      subjects aged 12 to 50 with persistent asthma.

      ELLIPTA, ACCUHALER, and DISKUS are registered trademarks of the GlaxoSmithKline group of
      companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent: Subjects must give their signed and dated written informed consent
             to participate prior to commencing any study related activities.

          -  Age Range: 12 to 50 years of age, inclusive, at Visit 1 (Screening).

          -  Diagnosis: A diagnosis of asthma, as defined by the National Institutes of Health for
             at least 12 weeks prior to Visit 1.

          -  Asthma Severity: Subjects must have a pre-bronchodilator FEV1 of >=70 percent of the
             predicted normal value. Predicted values will be based upon Global Lung Function
             Initiative equations for spirometry reference values.

          -  Evidence of EIB: Subjects must answer "Yes" to at least 2 of the following 3 questions
             reflecting on the previous 12 months:

               -  Are you short of breath during exercise or other physical exertion?

               -  Do you wheeze after exercise or other physical exertion?

               -  Do you cough after exercise or other physical exertion?

          -  Concurrent Anti-Asthma Therapy: Subjects must be taking low- to moderate dose inhaled
             steroids for 12 weeks prior to Visit 1 in order to participate with no change in dose
             for the 4 weeks prior to Visit 1.

          -  Gender: Subjects may be male or an eligible female. A female is eligible to enter and
             participate in the study if she is of: Non-child bearing potential (i.e.,
             physiologically incapable of becoming pregnant, including any female who is
             post-menopausal or surgically sterile).Surgically sterile females are defined as those
             with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation.
             Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with
             an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of
             hormone replacement therapy.

        OR Child bearing potential, has a negative pregnancy test at screening, and agrees to
        acceptable contraceptive methods approved in their local country, when used consistently
        and correctly (i.e., in accordance with the approved product label and the instructions of
        the physician for the duration of the study - screening to follow-up contact).

          -  Albuterol/salbutamol Use: All subjects must be able to replace their current
             short-acting beta2-agonist with albuterol/salbutamol, to be used only on an as-needed
             basis for the duration of the study. Each subject must be judged capable of
             withholding albuterol/salbutamol for at least 6 hours prior to performing spirometric
             evaluations.

          -  Physical Capacity: Each subject must be physically able to perform the exercise
             challenges on a treadmill when bronchodilators have been withheld.

        Exclusion Criteria:

          -  Intermittent Asthma, Seasonal Asthma, or Exercise-Induced Bronchoconstriction Only:
             Subjects with only intermittent or seasonal asthma or only exercise-induced asthma are
             excluded from participation in this study.

          -  History of Life-threatening Asthma: Defined for this protocol as an asthma episode
             that required intubation and/or was associated with hypercapnia, respiratory arrest or
             hypoxic seizures within the last 10 years.

          -  Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12
             weeks of Visit 1 or that resulted in an overnight hospitalization requiring additional
             treatment for asthma within 6 months prior to Visit 1.

          -  Symptomatic Allergic Rhinitis: Subjects with symptomatic allergic rhinitis at Visit 1
             may be treated for up to four weeks with intranasal corticosteroids followed by a
             repeat screening visit to determine eligibility prior to entry into the study.
             Subjects that continue to be symptomatic after up to four weeks of treatment will be
             excluded.

          -  12-Lead Electrocardiogram (ECG): A subject is not eligible if he/she has an abnormal,
             clinically significant ECG as determined by the investigator at the Screening Visit.

          -  Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
             during the study.

          -  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, is expected to affect the subject's asthma status or the subject's
             ability to participate in the study.

          -  Concurrent Respiratory Disease: A subject must not have current evidence of:

             1. Atelectasis 2. Bronchopulmonary dysplasia 3. Chronic bronchitis 4. Chronic
             obstructive pulmonary disease (COPD) (current or past diagnosis including asthma/COPD
             overlap) 5. Pneumonia 6. Pneumothorax 7. Interstitial lung disease 8. Or any evidence
             of concurrent respiratory disease other than asthma.

          -  Other Concurrent Diseases/Abnormalities: A subject must not have any clinically
             significant, uncontrolled condition, or disease state 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 efficacy results if the condition/disease
             exacerbated during the study.

          -  Investigational Medications: A subject must not have used any investigational drug
             within 30 days prior to Visit 1 or within five half-lives (t1/2) of the prior
             investigational study, whichever is longer of the two periods.

          -  Allergies: 1) Drug Allergy: Any adverse reaction including immediate or delayed
             hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal,
             inhaled, or systemic corticosteroid therapy, or excipients used with FF/VI 100/25 or
             FP 250 (i.e., drug, lactose or magnesium stearate). 2) Milk Protein Allergy: History
             of severe milk protein allergy. 3) Latex Allergy: History of allergy or sensitivity to
             latex that in the opinion of the investigator contraindicates the subject's
             participation in the study.

          -  Concomitant Medication: Administration of prescription or non-prescription medication
             that would significantly affect the course of asthma, or interact with study drug.

          -  Immunosuppressive Medications: A subject must not be using or require the use of
             immunosuppressive medications during the study.

          -  Compliance: A subject will not be eligible if he/she or his/her parent or legal
             guardian has any infirmity, disability, disease, or geographical location which seems
             likely (in the opinion of the investigator) to impair compliance with any aspect of
             this study protocol.

          -  Tobacco/Marijuana Use: Current tobacco smoker or has a smoking history of >=10
             pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled
             tobacco products or inhaled marijuana within the past 3 months (e.g. cigarettes,
             cigars, electronic cigarettes, or pipe tobacco).

          -  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 an employee of the participating investigator.