This study is being performed to comply with regulatory requirements that all new non-antiarrhythmic drugs must be assessed for potential effects on cardiac repolarization through electrocardiographic evaluation in a 'Thorough QT/ Corrected QT interval (TQT)' study. This will be a two part study, Part A will be an open-label, single oral dose study design in order to evaluate the pharmacokinetics, safety and tolerability of a 500 milligram (mg) dose of GSK1278863 and Part B will be a single-blind, randomized, placebo-controlled, single, oral dose, four-way crossover study design. Parts A and B will be conducted in healthy adult subjects with 12-lead electrocardiograms (ECGs), clinical laboratory safety tests, vital sign measurements, physical examinations, adverse event reports, and pharmacokinetic samples collected throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
61
A round, biconvex, white film coated tablet available in two doses (25 and 100 mg)
A round, biconvex, white film coated tablet available in two doses (25 and 100 mg)
Oblong, dull red, film-coated, convex tablets with M400 on one side
A round, biconvex, white film coated tablet as matching placebo for GSK1278863
Capsule shaped white film coated tablet as matching placebo for Moxifloxacin
GSK Investigational Site
Overland Park, Kansas, United States
Composite of pharmacokinetic (PK) parameters for GSK1278863 and its metabolites for Part A
Plasma concentrations of GSK1278863 and its metabolites (GSK2391220 \[M2\], GSK2506104 \[M3\], GSK2487818 \[M4\], GSK2506102 \[M5\], GSK2531398 \[M6\], and GSK2531401 \[M13\]) and derived pharmacokinetic parameters including maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Area under the concentration-time curve (AUC)
Time frame: Pre Dose, 0.25hour (h), 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 18h, and 24h post dose in each treatment period
Change from baseline in QT duration corrected for heart rate by Fridericia's formula (QTcF) interval for Part B
Change from baseline in QTcF interval at each time-point (average of at least three 12-lead Holter ECG replicates per time-point (Pre-dose, Day 1 \[0.25h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 18h\] and 24h) for 75 and 500 mg dose of GSK1278863 as compared with time-matched placebo
Time frame: At each treatment period (there are 4 periods) up to 24 hours
Assessment of 12-lead ECG for Part A
12-lead ECGs will be obtained at each time-point
Time frame: Up to Week 3
Assessment of Vital Signs for Part A
Vital Signs includes. temperature, systolic and diastolic blood pressure (BP) and pulse
Time frame: Up to Week 3
Number of participants with Adverse Events (AE) for Part A
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: Up to Week 3
Assessment of Clinical Laboratory Tests for Part A
Clinical Laboratory Tests includes Hematology, Clinical Chemistry and Urinalysis
Time frame: Up to Week 3
Change from baseline in QT duration corrected for heart rate by Bazett's formula (QTcB), heart rate (HR), PR, QRS, and QT interval corrected for heart rate (QTci/QTciL interval) for GSK1278863 for Part B
Change from baseline in QTcB, HR, PR, QRS and QTci/QTciL interval at each time-point (average of at least 3 12-lead Holter ECG replicates per time-point) for 75 mg and 500 mg dose of GSK1278863 as compared with time-matched placebo
Time frame: Up to Week 9
Change from baseline in QTcB, HR, PR, QRS, and QTci/QTciL interval for moxifloxacin for Part B
Change from baseline in QTcF, QTcB, and QTci/QTciL interval at each time-point (average of at least 3 12-lead Holter ECG replicates per time-point) for 400 mg dose of moxifloxacin as compared with time-matched placebo
Time frame: Up to Week 9
Composite of PK parameters for GSK1278863, its metabolites and moxifloxacin for Part B
Plasma concentrations of GSK1278863, and its metabolites GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13), moxifloxacin, and derived pharmacokinetic parameters including Cmax, tmax, AUC
Time frame: Pre-dose, 0.25h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 18h, and 24h in each treatment period of part B
Maximal change from baseline in ECG parameters for Part B
Maximal change from baseline in ECG parameters for QTcF and QTcB
Time frame: Up to Week 9
Change from baseline for other ECG parameters for Part B
Change from baseline at each time-point for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate
Time frame: Up to Week 9
Change in QTc Cmax for Part B
Evaluate the slope of the relationship and the predicted median (90% confidence interval \[CI\]) value of change in QTc Cmax following therapeutic doses
Time frame: Up to Week 9
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Assessment of Vital Signs for Part B
Vital Signs includes. temperature, systolic and diastolic blood pressure and pulse
Time frame: Up to Week 9
Number of participants with Adverse Events in Part B
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: Up to Week 9
Assessment of Clinical Laboratory Tests for Part B
Clinical Laboratory Tests includes Hematology, Clinical Chemistry and Urinalysis
Time frame: Up to Week 9
ECG assessment as a safety measure in Part B
Triplicate 12-lead ECGs will be obtained at each time-point (Day -1, Pre-dose, Day 1 \[0.25h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 18h\], Day 2 \[24h\])during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals
Time frame: Up to Week 9