This is an open-label, single-centre, non-randomized study to investigate the pharmacokinetics of GSK3191607, administered as a single intravenous (IV) dose in healthy male subjects. Six subjects will be administered an IV microdose of radio-labeled \[14C\]-GSK3191607. The study will provide an early readout on human pharmacokinetic parameters. The results of this study will be used to estimate the potential duration of anti-parasite effect in humans, define predicted clinical oral doses, and hence inform about the compound's potential safety margin. Each subject will participate in the study for up to 8 weeks, and will have a screening visit, one treatment period, eight outpatient visits, and a follow-up visit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
\[14C\]-GSK3191607 is a solution to be administered intravenously as a single dose infusion over 15 minutes. It is a radio-labeled product; 100 mcg of \[14C\]-GSK3191607 contains approximately 7.4 kilobecquerel (kBq) of \[14C\] radioactivity.
GSK Investigational Site
London, United Kingdom
Maximum observed concentration (Cmax) of GSK3191607 in plasma following a single intravenous (IV) microdose
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Terminal phase half life (t1/2) of GSK3191607 following a single IV microdose
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Time of occurrence of Cmax (tmax) of GSK3191607 following a single IV microdose
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
AUC(0-t) of GSK3191607 following a single IV microdose
AUC(0-t) is the area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
AUC(0-infinity) of GSK3191607 following a single IV microdose
AUC(0-infinity) is the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Systemic clearance (CL) of GSK3191607 following a single IV microdose
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
GSK3191607 volume of distribution at steady state (Vss)
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Cmax of radioactive drug-related material (RDM) in plasma following a single IV microdose of [14C]-GSK3191607
RDM is a measure of total radioactivity. Cmax of RDM will be compared with that of the parent drug (GSK3191607).
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
T1/2 of RDM following a single IV microdose of [14C]-GSK3191607
T1/2 of RDM will be compared with that of the parent drug.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Tmax of RDM following a single IV microdose of [14C]-GSK3191607
Tmax of RDM will be compared with that of the parent drug.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607
AUC(0-t) of RDM will be compared with that of the parent drug.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607
AUC(0-infinity) of RDM will be compared with that of the parent drug.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Amount of RDM excreted in urine (Ae) following a single IV microdose of [14C]-GSK3191607
Subjects will be asked to void their bladders before study treatment administration. A blank urine sample will be collected pre-dose.
Time frame: Pre-dose; and 0-24 hours and 24-48 hours after the start of infusion
Whole-Blood:Plasma ratio of Cmax of RDM following a single IV microdose of [14C]-GSK3191607
Cmax of RDM in whole blood will be compared with that of RDM in plasma.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Whole-Blood:Plasma ratio of tmax of RDM following a single IV microdose of [14C]-GSK3191607
Tmax of RDM in whole blood will be compared with that of RDM in plasma.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Whole-Blood:Plasma ratio of t1/2 of RDM following a single IV microdose of [14C]-GSK3191607
T1/2 of RDM in whole blood will be compared with that of RDM in plasma.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Whole-Blood:Plasma ratio of AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607
AUC(0-t) of RDM in whole blood will be compared with that of RDM in plasma.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Whole-Blood:Plasma ratio of AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607
AUC(0-infinity) of RDM in whole blood will be compared with that of RDM in plasma.
Time frame: Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion
Number of subjects with adverse events
Time frame: Start of infusion until follow-up (up to Day 25)
Number of subjects with clinically significant abnormal laboratory parameters
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Hematology, clinical chemistry, and urinalysis parameters will be evaluated.
Time frame: Day -1, Day 1, Day 2, and follow-up (up to Day 25)
Number of subjects with clinically significant abnormal 12-lead electrocardiogram (ECG) parameters
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Bazett's formula (QTcB) intervals.
Time frame: Pre-dose, Day 1, Day 2, and follow-up (up to Day 25)
Number of subjects with clinically significant abnormal vital signs parameters
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include systolic and diastolic blood pressure and pulse rate.
Time frame: Pre-dose, Day 1, Day 2, Day 3, and follow-up (up to Day 25)