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

Phase 2

Completed

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

Brief Summary: 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.

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)	FP/SAL 250/50mcg BID	FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)
FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)	GSK2190915 200mg QD (AM)	FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)
FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)	GSK2190915 100mg QD (AM)	FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)
FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)	Placebo capsule (PM)	FP/SAL 250/50mcg BID plus GSK2190915 300mg QD (AM)
FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)	FP/SAL 250/50mcg BID	FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)
FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)	Montelukast 10mg QD (PM)	FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)
FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)	Placebo tablets (2) (AM)	FP/SAL 250/50mcg BID plus montelukast 10mg QD (PM)
FP/SAL 250/50mcg BID plus placebo BID	FP/SAL 250/50mcg BID	P/SAL 250/50mcg BID plus placebo BID
FP/SAL 250/50mcg BID plus placebo BID	Placebo tablets (2) (AM)	P/SAL 250/50mcg BID plus placebo BID
FP/SAL 250/50mcg BID plus placebo BID	Placebo capsule (PM)	P/SAL 250/50mcg BID plus placebo BID

Primary Outcome Measures

Name	Time	Method
Trough (AM pre-dose and pre-rescue bronchodilator) FEV1	at the end of the 6 week treatment period.

Secondary Outcome Measures

Name	Time	Method
• 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.
• Percentage of symptom-free days	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.
• 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.
• Percentage of rescue-free days	during 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 nights	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.