A Study to Compare the Efficacy and Safety of Fluticasone Furoate (FF) 100 mcg Once Daily With Fluticasone Propionate (FP) 250 mcg Twice Daily (BD) and FP 100 mcg BD in Well-controlled Asthmatic Japanese Subjects
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone Furoate/Vilanterol; Fluticasone Furoate 100 mcg; Fluticasone Propionate 250 mcg; Fluticasone Propionate 100 mcg; Fluticasone Furoate Placebo; Fluticasone Propionate Placebo
Intervention description: FF/VI 100mg/25 mcg is available as a dry white powder to be given once daily in the evening via dry powder inhaler; FF 100 mcg is available as a dry white powder to be given once daily in the evening via dry powder inhaler; FP 250 mcg is available as a dry white powder to be given twice daily (morning and evening) via dry powder inhaler; FP 100 mcg is available as a dry white powder to be given twice daily (morning and evening) via dry powder inhaler; Matching placebo of Fluticasone Furoate will be given once daily in the evening via dry powder inhaler; Matching placebo of Fluticasone Propionate will be given twice daily (morning and evening) via dry powder inhaler
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 430.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: fluticasone propionate; step-down regimen; well-controlled subjects; adults; switching regimen; asthma; fluticasone furoate; fluticasone furoate/Vilanterol

Summary:

      The primary aim of this study is to clarify the position of FF and FF/Vilanterol (VI) 100/25
      micrograms (mcg) compared with existing therapies by assessing FF dosage equivalent to low to
      middle-dose inhaled corticosteroids (ICS). The study is divided into Run-in period, Period 1
      (open-label treatment), Period 2 (double blind treatment) and Follow-up. Subjects with well
      controlled asthma after completing a run-in period of 4 weeks will be switched from
      middle-dose ICS/long acting beta 2 agonist (LABA) equivalent dose to once-daily FF/VI 100/25
      mcg for an 8 weeks treatment period (Period 1). After this, subjects will be randomized in a
      1:1:1 ratio to receive either FP 250 mcg twice daily, FP 100 mcg twice daily or FF 100 mcg
      once daily in a 12 week double blind treatment period (Period 2). There will be a 1 week
      Follow-up Period following completion of the double-blind treatment period, or early
      withdrawal from the study. Overall , the total duration of subject's participation in the
      study will be for 25 weeks. RELVAR is a registered trademark of the GSK group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent: Subjects must give their signed and dated written informed consent
             to participate.

          -  Type of Subject: Outpatients 18 years of age or older at Visit 1. Subjects must have a
             diagnosis of asthma as defined by the National Institutes of Health at least 1 year
             prior to Visit 1.

          -  Gender: Male or Eligible Female, defined as non-childbearing potential or childbearing
             potential using an acceptable method of birth control consistently and correctly, as
             defined by the following: Male partner who is sterile prior to the female subject's
             entry into the study and is the sole sexual partner for that female subject; Oral
             contraceptive (either combined estrogen/progestin); Any intrauterine device (IUD) with
             a documented failure rate of less than 1% per year; Double barrier method - spermacide
             plus a mechanical barrier (e.g., spermacide plus a male condom or a spermacide and
             female diaphragm); Females of childbearing potential who are not sexually active must
             commit to complete abstinence from intercourse throughout the clinical trial and for a
             period after the trial to account for elimination of the drug (minimum of six days);
             Female subjects should not be enrolled if they are pregnant, lactating or plan to
             become pregnant during the time of study participation. A serum pregnancy test is
             required for females of childbearing potential at the initial screening visit (Visit
             1) and Visit 11 or Early Withdrawal. In addition a urine pregnancy test will be
             performed on all females of childbearing potential at Visit 2, Visit 5 and Visit 12.

          -  Severity of Disease: A best pre-bronchodilator FEV1 of >=80% of the predicted normal
             value at the screening visit (Visit 1). Predicted values will be based upon National
             Health and Nutrition Examination Survey (NHANES) III. As subjects are Asian, the Asian
             adjustment will be used.

          -  Stable Asthma: Subjects must have stable asthma, as judged by the Investigator. This
             includes no change in asthma medication for at least 8 weeks prior to Visit 1 and an
             ACT score of >=20 at Visit 1.

          -  Current Anti-Asthma Therapy: All subjects must be using the middle-dose ICS/LABA which
             is equivalent to twice-daily combination of fluticasone propionate and salmeterol 250
             mcg for at least 12 weeks prior to the registration visit. In addition, the
             prescription of the middle-dose ICS/LABA shouldn't be changed at least 8 weeks prior
             to Visit 1.

          -  Short-Acting Beta2-Agonists (SABA): All subjects must be able to use salbutamol
             aerosol inhaler which will be provided as a rescue medication at Visit 1 during the
             study as needed. Subjects must be able to avoid using salbutamol for at least 6 hours
             prior to study visits.

          -  12-lead electrocardiogram (ECG): Evidence of significant normality in the 12-lead ECG
             performed at Visit 1, as judged by the investigator Selected specific ECG findings
             that are not considered to be significant and will not exclude the subject from study
             participation include, but are not limited to, the following: T interval corrected for
             heart rate (QTc) <450 milliseconds (msec) or QTc <480 msec for patients with bundle
             branch block. The QTc is the QT interval corrected for heart rate according to
             Fridericia's formula (QTcF), machine overread. The QTc should be based on single or
             averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief
             recording period. If there are any clinically significant abnormalities including but
             not limited to a T interval for heart rate (QT) prolonged, confirm with two additional
             ECGs taken.

        Other inclusion criteria at Visit 2 and Visit 5:

          -  Subjects whose asthma meets the criterion of "well-controlled" (as defined in the
             protocol), and in the Investigators judgement it is acceptable for subject to "switch
             (Visit 2)" and "step-down (Visit 5)" in one week prior to Visit 2 or Visit 5.

          -  Compliance rate of the middle-dose ICS/LABA which is equivalent to twice-daily
             combination of fluticasone propionate and salmeterol 250 mcg (Visit1- Visit 2) and
             FF/VI 100/25 mcg (Visit 2 - Visit5) should be achieved >=80%

          -  Compliance with completion of both morning and evening eDairy data fulfils >=5days in
             one week prior to Visit 2 and Visit 5.

        Exclusion Criteria:

          -  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.

          -  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
             8 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.

          -  Asthma Exacerbation: Any asthma exacerbation requiring systemic corticosteroids or
             injection within 12 weeks of Visit 1 or that resulted in overnight hospitalization
             requiring additional treatment for asthma within 6 months prior to Visit 1.

          -  Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia,
             pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia,
             chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other
             respiratory abnormalities 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. 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 (two
             or more measurements with systolic BP >160 millimeters of mercury (mmHg), or diastolic
             BP >100mmHg), recent or poorly controlled peptic ulcer, haematologic, hepatic, or
             renal disease, immunologic compromise, current malignancy (history of malignancy is
             acceptable only if subject has been in remission for one year prior to Visit 1
             (remission = no current evidence of malignancy and no treatment for the malignancy in
             the 12 months prior to Visit 1)), tuberculosis (current or untreated) [Subjects with a
             history of tuberculosis infection who have completed an appropriate course of
             antituberculous treatment may be suitable for study entry provided that there is no
             clinical suspicion of active or recurrent disease], Cushing's disease, Addison's
             disease, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, recent history
             of drug or alcohol abuse

          -  Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has
             clinical visual evidence of candidiasis at Visit 1.

          -  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).

          -  Allergies: 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 investigational product (i.e., lactose or magnesium stearate);
             Milk Protein Allergy: History of severe milk protein allergy.

          -  Concomitant Medication: Administration of prescription or over the counter medication
             that would significantly affect the course of asthma, or interact with study drug,
             such as: anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic
             antidepressants; beta-adrenergic blocking agents; phenothiazines and monoamine oxidase
             (MAO) inhibitors; Immunosuppressive Medications: A subject must not be using or
             require use of immunosuppressive medications during the study.

        Note: Immunotherapy for the treatment of allergies is allowed during the study provided it
        was initiated at least 4 weeks prior to Visit 1 and subjects remain in the maintenance
        phase for the duration of the study; Cytochrome P450 3A4 (CYP3A4) inhibitors: Subjects who
        have received a potent CYP3A4 inhibitor within 4 weeks of Visit 1 (e.g.,Clarithromycin,
        atazanavir, indinavir, itraconazole, ketoconazole, nefazadone, nelfinavir; ritonavir;
        saquinavir; telithromycin, troleandomycin, voriconazole, mibefradil, cyclosporine, etc).

          -  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, including visit schedule and completion of eDiaries and a paper
             medical conditions diary.

          -  Tobacco Use: Current smoker or a smoking history of 10 pack years (e.g., 20
             cigarettes/day for 10 years). A subject may not have used inhaled tobacco products
             within the past 3 months (i.e., cigarettes, cigars 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 employee of the participating Investigator.

        Other exclusion criteria at Visit 2 and Visit 5:

          -  Evidence of clinically significant abnormal laboratory tests during Visit 1which are
             still abnormal upon repeat analysis and are not believed to be due to disease(s)
             present. Each Investigator will use his/her own discretion in determining the clinical
             significance of the abnormality.

          -  Changes in asthma medication (excluding salbutamol inhalation aerosol provided at
             Visit 1).

          -  Occurrence of a culture-documented or suspected bacterial or viral infection of the
             upper or lower respiratory tract, sinus or middle ear during the run-in and the
             open-label treatment period 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.

          -  Any asthma exacerbation requiring systemic corticosteroids or injection or that
             resulted in overnight hospitalization requiring additional treatment for asthma.
             Clinical visual evidence of oral candidiasis at Visit 2 and Visit 5.

          -  Positive urine pregnancy test for all females of childbearing potential at Visit 2 and
             Visit 5

          -  Subjects that the investigator decides that it is impossible for subject to do "switch
             (Visit 2)" and "step-down (Visit 5)".