This study will be conducted in three parts (Part 1, Part 2 and Part 3). Part 1 of this study will evaluate the relative bioavailability of a single dose of GSK2140944 tablet formulation compared to the reference capsule formulation under fasted conditions. The effect of food on the pharmacokinetics (PK) of a single dose of the tablet formulation will also be assessed. Part 2 will evaluate the effect of repeat doses of itraconazole on the pharmacokinetics of GSK2140944 following a single dose. A decision will be made whether to use the current capsule formulation or the new tablet formulation in Part 2 based upon the safety and PK data obtained from Part 1. Part 3 is conditionally based upon progression of the tablet formulation from Part 1 and will evaluate the effect of food on the safety, tolerability, and pharmacokinetics of the tablet formulation following multiple doses in elderly healthy subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Immediate release capsule containing GSK2140944 and inactive formulation excipients with a unit dose strength of 500 mg
Immediate release tablet containing GSK2140944 and inactive formulation excipients with a unit dose strength of 750 mg
Capsule containing Itraconazole with a unit dose strength of 100 mg
GSK Investigational Site
Overland Park, Kansas, United States
Part 1: Composite of PK parameters following GSK2140944 administration in fasted and fed state
PK parameters will include area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time AUC(0-infinity), AUC from time zero to last quantifiable concentration AUC(0-t), relative bioavailability of drug (Frel), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), lag time before observation of drug concentration (tlag) and terminal phase half-life (t1/2) in the fasted state; AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax after moderate fat meal.
Time frame: Day 1 (Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h)
Part 2: Composite of PK parameters of GSK2140944 following repeat oral dosing of itraconazole
PK parameters will include AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax of GSK2140944.
Time frame: Day 1 and Day 7 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and 48h post dose and also at 60h and 72h post dose on Day 7
Part 3: Safety and tolerability of GSK2140944 as assessed by adverse events (AEs)
Time frame: Approximately 8 weeks
Part 3: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications
Time frame: Approximately 8 weeks
Part 3: Safety and tolerability of GSK2140944 by laboratory assessments
Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
Time frame: Approximately 8 weeks
Part 3: Safety and tolerability of GSK2140944 as assessed by 12-lead electrocardiograms (ECGs)
All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes
Time frame: Approximately 8 weeks
Part 3: Safety and tolerability of GSK2140944 as assessed by vital signs
Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature
Time frame: Approximately 8 weeks
Part 1: Safety and tolerability of GSK2140944 as assessed by AEs
Time frame: Approximately 7 weeks
Part 1: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications
Time frame: Approximately 7 weeks
Part 1: Safety and tolerability of GSK2140944 by laboratory assessments
Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
Time frame: Approximately 7 weeks
Part 1: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs
All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes
Time frame: Approximately 7 weeks
Part 1: Safety and tolerability of GSK2140944 as assessed by vital signs
Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature
Time frame: Approximately 7 weeks
Part 2: Safety and tolerability of GSK2140944 as assessed by AEs
Time frame: Approximately 6 weeks
Part 2: Safety and tolerability of GSK2140944 by laboratory assessments
Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
Time frame: Approximately 6 weeks
Part 2: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs
All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes
Time frame: Approximately 6 weeks
Part 2: Safety and tolerability of GSK2140944 as assessed by vital signs
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Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature
Time frame: Approximately 6 weeks
Part 3: Composite of PK parameters of GSK2140944 following repeat oral dosing of GSK2140944
PK parameters will include AUC over the dosing interval (0-tau), tmax, tlag, t1/2, pre-dose (trough) concentration at the end of the dosing interval (Ctau) and Cmax of GSK2140944
Time frame: Day 3 and Day 4 (Pre-dose), Day 5 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h)