A 3-period Crossover Study With GSK573719 as Monotherapy in Adult Subjects With Asthma

Study Summary

This is a multi-national, randomized, double-blind, 3-period crossover, incomplete block design to evaluate 5 once-daily and 2 twice-daily doses of GSK573719 in combination with placebo. The study will explore the dose range of GSK573719 in asthmatic subjects who are currently using non-ICS controller medications. Subjects will participate in the study for up to a maximum of 14 weeks. At randomization subjects will be stratified by age to ensure adequate exposure to GSK573719 throughout the expected age range. The primary endpoint will be trough FEV1 obtained 24 hours after the last morning dose on Day 14 of each treatment sequence. A sub-group of subjects at selected sites (approximately 30% of the total population) will have additional serial assessments for spirometry, ECG and Holter, and pharmacokinetic sampling at the start and end of each treatment period. Safety assessments will include monitoring for adverse events, laboratory tests, asthma symptom assessments and twice daily PEF evaluation. Consenting subjects will have a blood sample taken for pharmacogenetic analysis.

Primary Outcome

Dose-response was conducted for both QD and BID UMEC doses on trough FEV1 (measure of lung function, defined as the maximal amount of air that can be forcefully exhaled in 1 second) on D 15. Total daily dose of UMEC was used in the modeling. The null model was the final model. The null model is defined as: CFEV1,ij=(THETA1+ETA1j)\*meanBL+(THETA2+ETA1j)\*periodBL+EPSij, where CFEV1,ij represents the change from BL in trough FEV1 for participant j measured at period i. THETA1 and THETA2 were the s

Interventions

• DRUG GSK573719 Active treatment or Placebo
• PROCEDURE GSK573719 (Sub-group cohort)
• DRUG Salbutamol/Albuterol