Dose Ranging Study Evaluating the Efficacy and Safety of GSK2190915 Administered Once Daily

A Randomised Double-Blind, Double-Dummy, Placebo-Controlled, Stratified, Parallel-Group, Multicentre, Dose Ranging Study to Evaluate the Efficacy and Safety of GSK2190915 Tablets Administered Once Daily, Fluticasone Propionate Inhalation Powder 100mcg Twice Daily and Montelukast 10mg Once Daily Compared With Placebo for 8 Weeks in Adolescent and Adult Subjects With Persistent Asthma While Treated With Short Acting Beta2-agonist.

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.

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