This will be a two-part study in healthy adults. Part A is a phase 1, non-randomized, open label, single-dose, single-centre mass balance study utilizing a radiolabeled dose to investigate the recovery, excretion, and pharmacokinetics of oral GSK1265744 in a cohort of 6 healthy adult male subjects. Subjects will undergo a pre-study screening visit within 30 days of the first dose and those who successfully pass pre-study assessments and meet eligibility criteria will be enrolled into the study to receive the equivalent of a 30 mg dose of GSK1265744 as an oral solution, containing approximately 70 microcuries (mcg Ci) \[0.96 millisieverts (mSv)\] of radioactivity under fasted conditions. Blood, urine and fecal samples will be collected for a maximum of 504 hours (21 days) following study drug administration. In Part B, approximately 10 healthy male and female subjects will be enrolled to evaluate the single-dose safety, tolerability and PK of supratherapeutic dose of GSK1265744 150 mg compared with placebo. Each subject will receive a single dose of GSK1265744 150 mg or placebo on Day 1 under fasting conditions in the morning. Blood, urine and fecal samples will be collected for 336 hours (14 days) following dosing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
16
A white to slightly colored nonsterile crystalline powder for oral solution
This is GSK1265744B (sodium salt of GSK1265744), lactose monohydrate, Microcrystalline cellulose, hypromellose, sodium lauryl sulfate, croscarmellose sodium, magnesium stearate, Opadry film-coating, white OY-S-28876 tablet
Microcrystalline cellulose, Opadry film-coating, white OY-S-28876 tablet
GSK Investigational Site
Overland Park, Kansas, United States
Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces.
Measurement of total radioactivity present in individual samples (plasma, urine, and feces) collected for a minimum of 336 hours (14 days) post dose up to a maximum of 504 hours (21 days).
Time frame: Up to 21 days
Part A: Composite of plasma GSK1265744 PK parameters to access total radioactivity in blood
The PK parameters will include: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a profile \[AUC (0-t)\], Area under the concentration-time curve from time zero (predose) extrapolated to infinite time \[AUC (0-infinity)\], Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Terminal phase elimination rate constant (lambda z), apparent terminal phase half-life (t1/2), and oral clearance (CL/F) of plasma GSK1265744 and total radioactivity in plasma and blood following single dose.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 288, 312 and 336 hours post dose.
Part B: Number of participants with the use of concurrent medication as a measure of safety and tolerability
Time frame: Up to 14 days
Part B: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 14 days
Part B: Composite of plasma GSK1265744 PK parameters
Plasma GSK1265744PK parameters following a single-dose administration of 150 mg under fasted conditions will include: AUC (0-t)\], AUC (0-infinity), Cmax, tmax, lambda z, t1/2, and oral clearance (CL/F) of plasma
Time frame: Up to 14 days
Part A: Blood: Plasma ratio of total drug-related material (radioactivity)
The blood: plasma ratio of total radioactivity (Cb/Cp) will be calculated at each time point by Clinical Statistics at GSK.
Time frame: Up to 21 days
Part A: Percent of total radioactivity associated with red blood cells
Percent of total radioactivity associated with red blood cells will be calculated based on radioactivity concentration in plasma and blood and hematocrit count.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 21 days
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