This is a randomized, placebo controlled, four period incomplete block,crossover thorough QT study to estimate the effect of repeat dose GSK573719/GW642444M (Vilanterol) combination and GSK573719 monotherapy on the QTc interval in healthy male and female subjects compared with placebo. At least 100 subjects will receive, four of five possible, 10-day repeat dose treatments. Treatments are placebo with a moxifloxacin placebo on day 10, placebo with moxifloxacin (400mg) on day 10, GSK573719/Vilanterol combination (125/25μg) with moxifloxacin placebo on day 10, GSK573719/Vilanterol combinatio (500/100μg) with moxifloxacin placebo on day 10, or GSK573719 (500μg) with a moxifloxacin placebo on day 10. All treatments are double blind except for moxifloxacin (400mg) and moxifloxacin placebo controls, given as a single-blind single dose on Day 10 of the appropriate treatment period. Primary endpoints are individual time-matched changes from baseline QTcF for GSK573719/Vilanterol combination (125/25μg) and GSK573719 (500μg), 0-24 hours after dosing on Day 10. Secondary endpoints will include individual time-matched changes from baseline in QTcF for GSK573719/Vilanterol combination (500/100μg) and moxifloxacin (400mcg) 0-24 hours after dosing on Day 10. Also changes from baseline in QTci, QTcB, QT, QRS, RR, PR and ventricular rate at each time point after 10 days dosing of each GSK573719 and GSK573719/Vilanterol treatment and single dose moxifloxacin (400mg). Maximal change from baseline 0-24hours after dosing on day 10 will be derived for QTcF, QTci and QTcB for each treatment. Plasma concentrations on Day 10 (0-24 hours) and pharmacokinetic parameters of GSK573719 and Vilanterol will also be derived. Key assessments: 12- lead electrocardiogram (ECG), pharmacokinetics. Safety will be assessed by blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events (AEs).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
100
Single dose placebo oral tablet Moxifloxacin
Single oral dose tablet Moxifloxacin (400mg)
Single inhalation from GSK573719/Vilanterol 125/25mcg DPI once daily
Single inhalation from GSK573719 500mcg DPI once daily
Single inhalation from GSK573719/Vilanterol 500/100mcg DPI once daily
Single Inhalation from matching Placebo DPI once daily
GSK Investigational Site
London, United Kingdom
Change from baseline in QTcF Interval with GSK573719/ Vilanterol 125/25mcg
To estimate the effect of GSK573719/ Vilanterol 125/25mcg on the QTcF interval as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTcF Interval with GSK573719 500 mcg
To estimate the effect of GSK573719 500 mcg (four times the highest combination dose being evaluated in Phase III trials) on the QTcF interval as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTcF interval with GSK573719/Vilanterol 500/100mcg
To estimate the effect of GSK573719/ Vilanterol 500/100mcg (four times the highest combination dose being evaluated in Phase III trials) on the QTcF interval as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTci and QTcB interval for GSK573719/Vilanterol 125/25mcg and 500/100mcg as compared with timematched placebo.
To estimate the effect of GSK573719/Vilanterol 125/25mcg and 500/100mcg on the QTci and QTcB interval interval as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTci and QTcB interval for GSK573719 500mcg as compared with time-matched placebo.
To estimate the effect of GSK573719 500mcg, on the QTci and QTcB interval interval as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTcF interval for moxifloxacin as compared with time-matched placebo.
To estimate the effect of a single oral dose of 400mg moxifloxacin on the QTcF interval as compared with placebo on day 10.
Time frame: Screening, Day 1, and Day 10
Change from baseline in QTci and QTcB interval for moxifloxacin as compared with time-matched placebo.
To estimate the effect of a single oral dose of 400mg moxifloxacin on the QTci and QTcB interval interval as compared with placebo on day 10.
Time frame: Screening, Day 1, and Day 10
Change from baseline at each timepoint on Day 10 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate for each active treatment compared with placebo.
To estimate the effect of all active treatments on other cardiac electrophysiological parameters as compared with placebo after 10 days dosing.
Time frame: Screening, Day 1, and Day 10
Plasma concentrations of GSK573719 and Vilanterol and derived pharmacokinetic parameters including Cmax, tmax and AUC(0-τ).
To characterise the pharmacokinetic profiles of GSK573719 and Vilanterol when administered in combination via novel DPI.
Time frame: Screening, Day 1, and Day 10
Plasma concentrations of GSK573719 and derived pharmacokinetic parameters including Cmax, tmax and AUC(0-τ).
To characterise the pharmacokinetic profile of supra-therapeutic dose of GSK573719 when administered as monotherapy via novel DPI.
Time frame: Screening, Day 1, and Day 10
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