This first time in human (FTIH) study assesses the safety, tolerability, and pharmacokinetics (PK) of single and multiple increasing doses of GSK2556286. It also includes food effect cohorts to evaluate how food influences the PK of GSK2556286. The findings will help determine appropriate dosing for future clinical studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
92
GSK2556286 will be administered.
Placebo will be administered
GSK Investigational Site
Groningen, Netherlands
GSK Investigational Site
Cambridge, United Kingdom
Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs
Time frame: Up to Day 15
Part B: Number of participants with any SAEs and non-SAEs
Time frame: Up to Day 28
Part A: Number of participants with AEs (SAEs and non-SAEs) by severity
Time frame: Up to Day 15
Part B: Number of participants with AEs (SAEs and non-SAEs) by severity
Time frame: Up to Day 28
Part A: Plasma concentrations of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Area under the plasma drug concentration versus time curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Maximum observed plasma drug concentration (Cmax) of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
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Part A: Apparent terminal half-life (T1/2) of GSK2556286
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Plasma concentrations of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose. Day 12 and 13: Pre-dose
Part B: AUC(0-t) of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: AUC(0-inf) of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Area under the plasma drug concentration versus time curve from time zero during a dosage interval of time tau (AUC[0-tau)] of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Cmax of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Tmax of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Trough plasma concentration (Ctau) of GSK2556286
Time frame: Pre-dose on Days 1, 12, 13 and 14
Part B: T1/2 of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Cmax of GSK2556286 under fasted and fed conditions
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Tmax of GSK2556286 under fasted and fed conditions
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: T1/2 of GSK2556286 under fasted and fed conditions
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Dose proportionality of GSK2556286 based on AUC(0-inf)
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Dose proportionality of GSK2556286 based on AUC(0-t)
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Dose proportionality of GSK2556286 based on Cmax
Time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Dose proportionality of GSK2556286 based on AUC(0-tau)
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Dose proportionality of GSK2556286 based on Cmax
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro])
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax)
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Steady state ratio (Rss) of GSK2556286
Time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Ctau at the end of the dosing interval to assess steady state of GSK2556286
Time frame: Pre-dose on Days 1, 12, 13 and 14