Dose Ranging Study Evaluating the Efficacy and Safety of GSK2190915 Administered Once Daily
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone Propionate 100mcg via ACCUHALER/DISKUS; GSK2190915 100mg; GSK2190915 10mg; GSK2190915 300mg; GSK2190915 30mg; Montelukast 10mg; Placebo GSK2190915 one tablet; Placebo montelukast; Placebo fluticasone propionate via ACCUHALER/DISKUS; Placebo GSK2190915 two tablets
Intervention description: Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS; GSK2190915 100mg (1 x 100mg) once daily in the morning; GSK2190915 10mg (1 x 10mg) once daily in the morning; GSK2190915 300mg (1 x 100mg, 1 x 200mg tablets) once daily in the morning; GSK2190915 30mg (1 x 30mg) once daily in the morning; Montelukast 10mg (1 x 10mg capsule) once daily in the evening; Placebo tablet, one tablet once daily in the morning; Placebo capsule once daily in the evening; Inhaled placebo twice daily via ACCUHALER/DISKUS; Placebo tablet, two tablets once daily in the morning
Intervention MeSH terms: Fluticasone; Xhance; Montelukast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 700.0
Sex: Female
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Efficacy; Asthma; Safety; Fluticasone Propionate; FLAP; Beta-agonists; GSK2190915; Montelukast; Placebo; FLAIR

Summary:

      To evaluate the efficacy, dose response and safety of four doses of GSK2190915 in tablet form
      (10mg, 30mg, 100mg and 300mg) administered once daily, over 8 weeks compared with placebo in
      adolescent and adult subjects (12 years of age and older) with persistent asthma. These data
      will form the basis for the selection of the optimal daily dose of GSK2190915 to be carried
      forward in Phase III asthma studies. The study also includes Fluticasone Propionate
      Inhalation Powder (100 mcg, twice daily) and Montelukast (10mg, once daily) to allow for an
      exploratory analysis of the efficacy of GSK2190915 versus a low dose inhaled corticosteroid
      and a leukotriene receptor antagonist.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type of Subject: Outpatient

          -  Age: ≥12 years of age

          -  Gender: Eligible Female (females of childbearing potential must commit to consistent
             and correct use of an acceptable method of birth control)

          -  Asthma Diagnosis: As defined by NIH

          -  Severity of Disease: FEV1 50-85% predicted AND in current and former smokers a post
             salbutamol/albuterol ratio >0.70

          -  Reversibility: ≥12% and ≥200mL in FEV1 within 30 ±15 minutes following
             salbutamol/albuterol

          -  Current anti-asthma therapy: Using short-acting beta-agonist (SABA) for ≥3 months

          -  Tobacco use: Non-smoker /former smoker with ≤10 pack years or current smoker with ≤10
             pack years

          -  QTC: QTc(F)<450msec or QTc(F)<480 for subjects with Bundle Branch Block

          -  Liver function: Normal liver function

          -  Informed Consent

        Exclusion Criteria:

          -  History of Life-threatening asthma: Within previous 5 years

          -  Asthma Exacerbation: Requiring OCS within 3 months or hospitalisation within 6 months

          -  Respiratory Infection: Not resolved within the 4 weeks before V1 AND led to a change
             in asthma management OR treatment with antibiotics OR is expected to affect the
             subject's asthma status or ability to participate

          -  Corticosteroid Use: ICS used within 6 weeks or OCS/depot corticosteroids within 12
             weeks

          -  OATP1B1 substrates: OATP1B1 substrates (e.g. statins, rifampicin,
             bromosulphophthalein, benzylpenicillin, methotrexate) within 4 weeks

          -  Immunosuppressive medications: Either using or required during the study

          -  Liver disease: Current or chronic history

          -  Concurrent disease/abnormalities: Clinically significant uncontrolled disease

          -  Investigational medications: Participation in a study or used investigational drug
             within 30 days

          -  Drug allergy: β-agonists, corticosteroids, constituents of inhalers

          -  Milk Protein Allergy: History of severe milk protein allergy

          -  Compliance: Factors likely to impair compliance either with regards to study
             medication, procedures or attendance

          -  Unable or unwilling to follow instructions: Procedures, dosing directions, e-diaries
             or pMDIs

          -  History of alcohol or drug abuse: Likely to interfere with the study

          -  Affiliation with Investigator's Site: Relative or employee