A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Five-Treatment, Four 6-Week Period Cross-Over, Multi-Center Study to Evaluate the Effect of Adding GSK2190915 100mg, GSK2190915 300mg, Montelukast 10mg or Placebo Tablets Once Daily or Salmeterol 50mcg Inhalation Powder Twice Daily to Fluticasone Propionate 100mcg Inhalation Powder Twice Daily in Uncontrolled Asthmatic Subjects ≥ 12 Years of Age
Overview
- Phase
- Phase 2
- Intervention
- FP 100
- Conditions
- Asthma
- Sponsor
- GlaxoSmithKline
- Enrollment
- 162
- Locations
- 1
- Primary Endpoint
- Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 100mg, GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate 100mcg inhalation administered twice daily in uncontrolled asthmatic subjects > or = 12 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 or salmeterol 50mcg administered twice daily to fluticasone propionate 100mcg inhalation administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects > or = 12 years of age over the course of 6 weeks treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: 12 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
- •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 100mcg inhalation powder BID for at least 2 weeks just prior to Visit
- •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
- Not provided
Arms & Interventions
FP 100mcg BID plus GSK2190915 100mg QD (AM)
FP 100mcg BID plus GSK2190915 100mg QD (AM)
Intervention: FP 100
FP 100mcg BID plus GSK2190915 100mg QD (AM)
FP 100mcg BID plus GSK2190915 100mg QD (AM)
Intervention: GSK2190915 100
FP 100mcg BID plus GSK2190915 300mg QD (AM)
FP 100mcg BID plus GSK2190915 300mg QD (AM)
Intervention: FP 100
FP 100mcg BID plus GSK2190915 300mg QD (AM)
FP 100mcg BID plus GSK2190915 300mg QD (AM)
Intervention: GSK2190915 300
FP 100mcg BID plus montelukast 10mg QD (PM)
FP 100mcg BID plus montelukast 10mg QD (PM)
Intervention: FP 100
FP 100mcg BID plus montelukast 10mg QD (PM)
FP 100mcg BID plus montelukast 10mg QD (PM)
Intervention: montelukast
FP 100mcg BID plus placebo BID
FP 100mcg BID plus placebo BID
Intervention: FP 100
FP 100mcg BID plus placebo BID
FP 100mcg BID plus placebo BID
Intervention: placebo
FP/SAL 100/50mcg BID plus placebo BID
FP/SAL 100/50mcg BID plus placebo BID
Intervention: placebo
FP/SAL 100/50mcg BID plus placebo BID
FP/SAL 100/50mcg BID plus placebo BID
Intervention: FP/SAL 100/50
Outcomes
Primary Outcomes
Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period
Time Frame: End of Week 6
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically using spirometry, prior to study medication and any rescue albuterol (bronchodilator) use. At the end of the 6-week treatment period, FEV1 was measured approximately 24 hours after the participant's last morning dose of study medication and approximately 12 hours after the evening dose of study medication. Trough FEV1 was analyzed using mixed effect analysis of covariance (ANCOVA) model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effect of participant. Intent-to-Treat Population is defined as all participants who were randomized and received at least one dose of study drug.
Secondary Outcomes
- Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups(Week 4 to Week 6)
- Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)
- Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period(Week 4 to Week 6)
- Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period(Week 4 to Week 6)