A Phase IIA FF/VI Study to Measure FeNO in Asthmatic Patients.
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone furoate (FF) (100 mcg); Vilanterol (VI) (25 mcg); Placebo
Intervention description: First blister strip contains FF blended with lactose, 100 mcg per blister; Second blister strip contains vilanterol blended with lactose and magnesium stearate, 25 mcg per blister; Matching placebo will have two blister strips, identical in appearance to the inhaler containing active study medication; one containing lactose and the second strip containing lactose and magnesium stearate
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Fluticasone furoate/vilanterol; Asthma; fraction of exhaled nitric oxide; cross-over

Summary:

      For asthmatic subjects, a combination of inhaled corticosteroid (FF) and long-acting beta2
      receptor agonist (VI) is recommended for use (once daily) and fraction of exhaled nitric
      oxide (FeNO) is a non-invasive airway inflammation marker.

      In this randomised, double blind, placebo-controlled, two-period, crossover repeat dose
      study, the duration of action of fluticasone furoate (FF) will be determined by monitoring
      the return of FeNO levels to baseline, following the treatment with FF/vilanetrol (VI) in
      asthmatic subjects.

      Subjects who meet the eligibility criteria will participate in the following two treatment
      periods: FF/VI 100/25 mcg once-daily and placebo once-daily. Approximately 28 subjects will
      be enrolled in order to achieve 24 evaluable subjects. A 2-week treatment period will be
      followed by a 21-day monitoring/washout period before crossing over to the next treatment
      period. Total duration of each subject will be a maximum of 21 weeks. FeNO will be monitored
      up to 21 days after treatment with FF/VI together with FEV1 (up to 7 days).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age of subject: Between 18 and 65 years of age inclusive, at the time of signing the
             informed consent.

          -  A doctor diagnosis of asthma for at least 6 months prior to the start of the study.

          -  Severity of disease: A screening pre-bronchodilator forced expiratory volume in one
             second (FEV1) >=60% of predicted values, which will be based upon NHANES III

          -  Reversibility of disease: Demonstrated presence of reversible airway disease at
             screening (repeat testing of eligibility can be undertaken following the screening
             visit up to Day -7) OR The presence of reversible airways disease can have been
             demonstrated historically within 6 months of the screening visit. Reversible airway
             disease is defined as increase in FEV1 of >=12% over baseline and an absolute change
             of >=200 mL within 30 minutes following 4 inhalations of albuterol/salbutamol
             inhalation aerosol/spacer (or equivalent nebulised treatment with albuterol/salbutamol
             solution).

          -  Current Therapy: Short-acting beta2-agonists (SABA) prescribed for at least 12 weeks
             prior to screening. No inhaled corticosteroids (ICS), long-actint beta2-receptor
             agonist (LABA), long acting muscarinic anatagonist (LAMA), leukotriene receptor
             antagonist (LTRA) therapy for three months prior to the start of the study.

          -  Non-smoker or ex-smoker (no smoking in previous 12 weeks, ≤10 pack years).

          -  Screening and Day -7 AM fraction of inhaled nitric oxide (FeNO) values > 40ppb. Both
             screening and Day -7 AM FeNO values for treatment Period 1 need to be > 40ppb for the
             subject to be eligible.

          -  Bodyweight and BMI: Bodyweight >=50 kg and body mass index (BMI) within the range 18.0
             40.0 kg/m2 (inclusive)

          -  Male OR Female:

          -  Females: A female subject is eligible to participate if she is not pregnant (as
             confirmed by a negative urine human chorionic gonadotrophin [hCG[ test), not
             lactating, and at least one of the following conditions applies: Non-reproductive
             potential defined as:

          -  Pre-menopausal females reporting one of the following:

        Tubal ligation Hysteroscopic tubal occlusion procedure with follow-up confirmation of
        bilateral tubal occlusion Hysterectomy Bilateral Oophorectomy

          -  Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a
             blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels
             consistent with menopause [refer to laboratory reference ranges for confirmatory
             levels]). Females on hormone replacement therapy (HRT) and whose menopausal status is
             in doubt will be required to use one of the highly effective contraception methods if
             they wish to continue their HRT during the study. Otherwise, they must discontinue HRT
             to allow confirmation of post-menopausal status prior to study enrolment.

          -  Reproductive potential and agrees to follow one of the options listed in the Modified
             List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
             Potential (FRP) from 30 days prior to the first dose of study medication and until
             after the last dose of study medication and completion of the follow-up visit

          -  The investigator is responsible for ensuring that subjects understand how to properly
             use these methods of contraception.

          -  Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form and in this protocol.

        Exclusion Criteria:

          -  A history of life-threatening asthma, which is defined as an asthma episode that
             required intubation and/or was associated with hypercapnia, respiratory arrest or
             hypoxic seizures within the last 5 years

          -  Other significant pulmonary diseases to include (but not limited to): pneumonia,
             pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia,
             chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other
             respiratory abnormalities other than asthma.

          -  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 screening that 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. However, subjects can be rescreened to allow for
             an adequate time period (of at least 4 weeks) between resolution of the infection and
             the date of randomisation.

          -  Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12
             weeks of screening or that resulted in overnight hospitalization requiring additional
             treatment for asthma within 6 months prior to screening.

          -  Pre-defined concomitant medications and restrictions of nitrate-rich foods

          -  Tobacco Use: Current smokers or a smoking history of >=10 pack years. A subject may
             not have used any inhaled tobacco products in 12 weeks preceding the screening visit.

          -  Previous Participation: Exposure to more than four new chemical entities within 12
             months prior to the first dosing day.

          -  Other concurrent Diseases/Abnormalities: A subject has 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 study results if the condition/disease exacerbated
             during the study.

          -  The list of additional excluded conditions/diseases includes, but is not limited to
             the following:

          -  Congestive heart failure-Known aortic aneurysm

          -  Clinically significant coronary heart disease-Clinically significant cardiac
             arrhythmia

          -  Stroke within 3 months of Visit 1-Uncontrolled hypertension

          -  Recent or poorly controlled peptic ulcer-Haematologic, hepatic, or renal disease

          -  Immunologic compromise-Current malignancy

          -  Tuberculosis (current or untreated)-Cushing's disease

          -  Addison's disease-Uncontrolled diabetes mellitus

          -  Liver cirrhosis-Systemic Lupus Erythematosus

          -  Uncontrolled thyroid disorder-Recent history of drug or alcohol abuse

          -  Oropharyngeal examination: A subject will not be eligible if he/she has clinical
             visual evidence of oral candidiasis at screening.

          -  Pregnancy and Lactating Females:

          -  Pregnant females as determined by positive serum hCG test at screening or by positive
             urine hCG test prior to dosing.

          -  Lactating females

          -  Allergies:

          -  Milk Protein Allergy: History of severe milk protein allergy.

          -  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 (DPI) (i.e., lactose or magnesium stearate).

          -  Historical Allergy: History of drug or other allergy that, in the opinion of
             investigator or GSK Medical Monitor, contraindicates their participation