Safety and Efficacy Study Adding GSK2190915 to Mid-dose Inhaled Corticosteroid/Long Acting Beta Agonist Combination Treatment for Asthma

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily in uncontrolled asthmatic subjects > or = 18 years of age over the course of 6 weeks treatment. The secondary objectives are to undertake an exploratory analysis of the efficacy and safety of adding montelukast 10mg administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects > or = 18 years of age over the course of 6 weeks treatment.

Official Title
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Three-Treatment, Three 6-Week Period Cross-Over, Multi-Center Study to Evaluate the Effect of Adding GSK2190915 300mg as Compared to Adding Montelukast 10mg or Placebo Tablets QD to Fluticasone Propionate/Salmeterol 250/50mcg Diskus BID

Conditions
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Asthma

Intervention / Treatment
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* Drug: FP/SAL 250/50mcg BID
* Drug: GSK2190915 200mg QD (AM)
* Drug: GSK2190915 100mg QD (AM)
* Drug: Montelukast 10mg QD (PM)
* Drug: Placebo tablets (2) (AM)
* Drug: Placebo capsule (PM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 years of age or older Non-, former or current smokers with a documented smoking history of ≤ 10 pack years Asthma diagnosis as defined by the National Institutes of Health Best FEV1 of 50% to <80% of the predicted normal value For current and former smokers, a post-albuterol FEV1/FVC ratio of >0.70 at Visit 1/1a (between 5:00AM and 12:00 noon) ≥ 12% and ≥200mL reversibility of FEV1 Must have been using FP/SAL 250/50mcg inhalation powder BID for at least 2 weeks just prior to Visit 1. Must be able to replace their current short-acting beta2-agonists with albuterol inhalation aerosol Must be able and willing to give written informed consent to take part in the study. Must be able and willing to comply with all aspects of the study including completion of daily e-Diary. Exclusion criteria: History of life-threatening asthma Recent asthma exacerbation Concurrent respiratory disease Recent respiratory infection Liver disease Other concurrent diseases/abnormalities Oral candidiasis Drug allergy Milk protein allergy Immunosuppressive Medications Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1 OATP1B1 substrates within 4 weeks of Visit 1 Cytochrome P450 3A4 (CYP 3A4) Inhibitors Cytochrome P450 3A4 (CYP 3A4) Inducers Investigational Medications Compliance: any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol Affiliation with Investigator's Site

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)<br>FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM) | Drug: FP/SAL 250/50mcg BID<br>* FP/SAL 250/50mcg BID<br>Drug: GSK2190915 200mg QD (AM)<br>* GSK2190915 200mg QD (AM)<br>Drug: GSK2190915 100mg QD (AM)<br>* GSK2190915 100mg QD (AM)<br>Drug: Placebo capsule (PM)<br>* Placebo capsule (PM)<br>|
| Active Comparator: FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)<br>FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM) | Drug: FP/SAL 250/50mcg BID<br>* FP/SAL 250/50mcg BID<br>Drug: Montelukast 10mg QD (PM)<br>* Montelukast 10mg QD (PM)<br>Drug: Placebo tablets (2) (AM)<br>* Placebo tablets (2) (AM)<br>|
| Placebo Comparator: FP/SAL 250/50mcg BID plus placebo BID<br>P/SAL 250/50mcg BID plus placebo BID | Drug: FP/SAL 250/50mcg BID<br>* FP/SAL 250/50mcg BID<br>Drug: Placebo tablets (2) (AM)<br>* Placebo tablets (2) (AM)<br>Drug: Placebo capsule (PM)<br>* Placebo capsule (PM)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough (AM pre-dose and pre-rescue bronchodilator) FEV1 |  | at the end of the 6 week treatment period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Daily trough (AM pre-dose and pre-rescue bronchodilator) AM PEF |  | averaged over the last 3 weeks of the 6 week treatment period. | 
| • Daily PM PEF |  | averaged over the last 3 weeks of the 6 week treatment period. | 
| • Daily (average of AM and PM) |  | averaged over the last 3 weeks of the 6 week treatment period | 
| • Daily asthma symptom score |  | averaged over the last 3 weeks of the 6 week treatment period. | 
| • Daily rescue salbutamol use |  | averaged over the last 3 weeks of the 6 week treatment period. | 
| • Percentage of symptom-free days |  | during the last 3 weeks of the 6 week treatment period. | 
| • Percentage of symptom-free nights |  | during the last 3 weeks of the 6 week treatment period. | 
| • Percentage of rescue-free days |  | during the last 3 weeks of the 6 week treatment period. | 
| • Percentage of rescue-free nights |  | during the last 3 weeks of the 6 week treatment period. | 
| • Percentage of nights without awakenings due to asthma |  | during the last 3 weeks of the 6 week treatment period. | 
| • Proportion of subjects withdrawn due to lack of efficacy |  | during the last 3 weeks of the 6 week treatment period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, GSK2190915