A Study in Asthmatic Patients to Determine if There is Any Difference in Dosing With Fluticasone Furoate/Vilanterol Inhalation Powder in the Morning or Evening on Lung Function
Condition: Asthma
MeSH terms: Respiratory Aspiration
Intervention: FF(100mcg)/Vilanterol(25mcg) AM; FF(100mcg)/Vilanterol(25mcg) PM; Placebo AM; Placebo PM
Intervention description: Inhalation powder; Inhalation powder; Inhalation powder; Inhalation powder
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Fluticasone furoate; Vilanterol; Efficacy; FEV1; FF/VI Inhalation powder

Summary:

      This study will be a repeat-dose, double-blind, randomized, placebo controlled, three-way
      crossover study in patients with persistent bronchial asthma to compare the effect of morning
      (AM) and evening (PM) dosing with fluticasone furoate (FF)/Vilanterol (VI) inhalation powder
      on lung function. Following screening there will be a run-in period of 14 days. There will be
      3 treatment periods; drug at AM, drug at PM and placebo, which will last for 14 days each
      with a 14-21 day washout period between starting the next. Key assessments include; forced
      expiratory volume in one second (FEV1), peak expiratory flow (PEF), vital signs,
      electrocardiograms (ECGs), adverse event (AE) monitoring and laboratory safety tests.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with a documented history of persistent asthma, with the exclusion of other
             significant pulmonary diseases.

          -  Male or female between 18 and 70 years of age inclusive

          -  A female subject is eligible to participate if she is of:

               -  Non-childbearing potential. Females on hormone replacement therapy (HRT) and
                  whose menopausal status is in doubt will be required to use one of the
                  contraception methods if they wish to continue their HRT during the study.
                  Otherwise, they must discontinue HRT to allow confirmation of postmenopausal
                  status prior to study enrollment.

               -  Child-bearing potential and agrees to use one of the protocol contraception
                  methods.

          -  All subjects must be using an inhaled corticosteroid (ICS), with or without a
             short-acting, beta2-receptor agonist (SABA), for at least 12 weeks prior to screening.

          -  Subjects with a screening pre-bronchodilator FEV1 ≥ 60% of predicted.

          -  During the screening visit, subjects must demonstrate the presence of reversible
             airway disease.

          -  All subjects must be able to replace all their current asthma treatments with
             albuterol/salbutamol aerosol inhaler at screening for use as needed for the run-in
             period and throughout the duration of the study. Subjects must be able to withhold
             albuterol/salbutamol for at least 6 hours prior to study visits.

          -  Subjects who are current non-smokers, who have not used any inhaled tobacco products
             in the 12 month period preceding the screening visit.

          -  Body weight ≥ 50 kg and Body Mass Index (BMI) within the range 19.0-29.9 kg/m2
             (inclusive).

          -  No evidence of significant abnormality in the 12-lead ECG performed at screening.

          -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2x Upper limit
             of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin
             >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

          -  Capable of giving written informed consent

          -  Able to satisfactorily use the novel dry powder inhaler.

        Exclusion Criteria:

          -  A history of life-threatening asthma within the last 5 years.

          -  Culture-documented or suspected bacterial or viral infection that is not resolved
             within 4 weeks of screening 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.

          -  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.

          -  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.

          -  A subject will not be eligible if he/she has clinical visual evidence of oral
             candidiasis at screening.

          -  Pregnant females.

          -  Lactating females.

          -  The subject has participated in a clinical trial and has received an investigational
             product within 30 days prior to the first dosing day in the current study.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Any adverse reaction including immediate or delayed hypersensitivity to any beta 2-
             agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid
             therapy.

          -  History of severe milk protein allergy.

          -  History of drug or other allergy that, in the opinion of the investigator or GSK
             Medical Monitor, contraindicates their participation.

          -  Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is
             a potential enzyme inducer) 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.

          -  Subjects who have taken high doses of an ICS within 8 weeks of the screening visit or
             oral steroids within 12 weeks of the screening visit.

          -  Subjects who have changed their ICS treatment within the last 4 weeks before screening
             or can be expected to do so during the study.

          -  History of regular alcohol consumption within 6 months of the study.

          -  A positive test for Hepatitis B or Hepatitis C within 3 months of screening.

          -  A positive breath carbon monoxide (CO) test.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period.

          -  No subject is permitted to perform night shift work for 1 week prior to screening
             until completion of the study treatment periods.

          -  Unwillingness or inability to follow the procedures outlined in the protocol.