A Study to Compare the Efficacy of Fluticasone Furoate/Vilanterol Inhalation Powder With Usual Inhaled Corticosteroids (ICS)/Long Acting Beta Agonists (LABA) in Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone Furoate; Vilanterol; Fluticasone propionate; Salmeterol; Budesonide; Formoterol Fumarate
Intervention description: FF 92 mcg or 184 mcg blended with lactose administered once daily via ELLIPTA DPI; Vilanterol 22 mcg blended with lactose and magnesium stearate administered once daily via ELLIPTA DPI; FP 250 mcg or 500 mcg blended with lactose administered twice daily via DISKUS DPI; Salmeterol 50 mcg blended with lactose administered twice daily via DISKUS DPI; Budesonide 200 mcg or 400 mcg blended with lactose administered twice daily via TURBUHALER DPI; Formoterol Furoate 6 mcg or 12 mcg blended with lactose administered twice daily via TURBUHALER DPI
Intervention MeSH terms: Fluticasone; Xhance; Budesonide; Formoterol Fumarate; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 423.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: dry powder inahler; vilanerol; efficacy; safety; fluticasone furoate; quality of life

Summary:

      The combination of FF, an ICS and VI, an orally inhaled LABA has been developed as a
      once-daily combination therapy for the long-term maintenance treatment of asthma in adults
      and children >=12 years of age. Pivotal phase III studies have demonstrated the safety and
      efficacy of FF/VI in asthma. However, it is increasingly acknowledged that randomised
      clinical trials tend to be highly controlled and enrol a more highly selected subject
      population than is expected to be prescribed the medication post-approval. There is a need
      for data in a more representative population in close to a 'real life' conditions, where
      physicians have the ability to choose the best treatment in their view for any individual
      subject and adapt treatments to subjects' characteristics and response. This multi-center,
      open-label, randomized, parallel group study will evaluate the efficacy and safety of FF/VI
      compared with two usual ICS/LABA fixed combination (fluticasone propionate/salmeterol [FP/S]
      or budesonide/formoterol [BUD/F]) in subjects with persistent asthma, in a "close to real
      life" settings. FF/VI will be administered once-daily (QD) via ELLIPTA dry powder inhaler
      (DPI) and FP/S or BUD/F will be administered twice daily (BID) via DISKUS™ and TURBUHALER™
      DPI respectively. ELLIPTA is a new powder inhaler designed to be easy to use. The total
      duration of subject participation will be approximately 6 months (24 weeks). ELLIPTA and
      DISKUS are registered trademarks of the GSK group of companies. TURBUHALER is a registered
      trademark of AstraZeneca.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent: Capable of giving signed informed consent which includes compliance
             with the requirements and restrictions listed in the consent form and in this
             protocol.

          -  Gender and Age: Male or female subjects aged >=18 and <=75years of age at Screening
             visit.

        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 with one of the following -
        Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with
        follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented 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 below in the GSK
        Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
        Potential (FRP) requirements from 30 days prior to the first dose of study medication and
        until Week 24.

        GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP:

        This list does not apply to FRP with same sex partners, when this is their preferred and
        usual lifestyle or for subjects who are and will continue to be abstinent from
        penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal
        implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including
        a <1percent rate of failure per year, as stated in the product label; Intrauterine device
        or intrauterine system that meets the SOP effectiveness criteria including a <1 percent
        rate of failure per year, as stated in the product label; Oral Contraceptive, either
        combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring;
        Percutaneous contraceptive patches; Male partner sterilization with documentation of
        azoospermia prior to the female subject's entry into the study, and this male is the sole
        partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film,
        cream, or suppository); These allowed methods of contraception are only effective when used
        consistently, correctly and in accordance with the product label. The investigator is
        responsible for ensuring that subjects understand how to properly use these methods of
        contraception.

          -  Type of subject: Subjects with documented physician's diagnosis of asthma >=1 year,
             unsatisfactorily controlled asthma (ACT <20 at Screening and Randomisation visit)
             treated by ICS alone and intended to be treated by ICS/LABA maintenance therapy;
             France Only: A subject will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a Social Security category.

          -  Current Asthma Therapy: All subjects must be prescribed maintenance therapy and
             receiving ICS alone without LABA for at least 4 weeks prior to Randomisation visit;
             Other background asthma medication such as anti-leukotrienes or theophylline is
             permitted as an alternative to ICS alone, if initiated at least 4 weeks prior to
             screening visit.

          -  Subject questionnaires Subjects must be able to complete the questionnaires
             themselves.

        Exclusion Criteria:

          -  History of Life-threatening asthma: Defined for this protocol as an asthma episode
             that required intubation and/or was associated with hypercapnea, respiratory arrest or
             hypoxic seizures within the last 6 months before Screening and Randomisation visit.

          -  Subjects having a severe and unstable asthma, with ACT score < 15 at Visit 1 and at
             Visit 2, and/or a history of repeated severe exacerbations (3/year) and/or a severe
             exacerbation in the previous 6 weeks before Visit 1 and Visit 2.

          -  Chronic obstructive pulmonary disease (COPD) Respiratory Disease: A subject must not
             have current evidence or diagnosis of chronic obstructive pulmonary disease at
             Screening visit.

          -  Current or former cigarette smokers with a history of cigarette smoking of >=10
             pack-years at screening [number of pack years = (number of cigarettes per day / 20) x
             number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per
             day for 20 years)].

          -  Other diseases/abnormalities: Subjects with historical or current evidence of
             uncontrolled or clinically significant disease at Screening and Randomisation visit.
             Significant is defined as any disease that, in the opinion of the Investigator, would
             put the safety of the subject at risk through participation, or which would affect the
             efficacy or safety analysis if the disease/condition exacerbated during the study.

          -  Subjects with a history of adverse reaction including immediate or delayed
             hypersensitivity to any intranasal, inhaled, or systemic corticosteroid and LABA
             therapy and to components of the inhalation powder (e.g., lactose, magnesium stearate)
             at Screening and Randomisation visit. In addition, subjects with a history of severe
             milk protein allergy that, in the opinion of the Investigator, contraindicates the
             subject's participation will also be excluded.

          -  Investigational Medications: A subject must not have used any investigational drug
             within 30 days prior to Randomisation visit or within five half-lives (t½) of the
             prior investigational study (whichever is longer of the two), (if unsure discuss with
             the medical monitor prior to screening).

          -  Chronic user of systemic corticosteroids: A subject who, in the opinion of the
             Investigator, is considered to be a chronic user of systemic corticosteroids for
             respiratory or other indications (if unsure discuss with the medical monitor prior to
             screening) at Screening visit.

          -  Subjects treated by the monoclonal antibody omalizumab or mepolizumab at Visit 1.
             Treatment with omalizumab or mepolizumab is not allowed during the study.

          -  Subjects involved in other clinical trials at Screening visit.

          -  Affiliation with Investigator Site: Is an investigator, sub-investigator, study
             coordinator, employee of a participating investigator or study site, or immediate
             family member of the aforementioned that is involved in this study.

          -  Subjects who plan to move away from the geographical area where the study is being
             conducted during the study.