Malaria, Falciparum
Conditions
Keywords
Malaria, Microdose, GSK3191607
Brief summary
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.
Interventions
DRUG[14C]-GSK3191607
\[14C\]-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.
Sponsors
Hammersmith Medicines Research
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 55 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>= 50 kg and body mass index (BMI) within the range 19.0-31.0 kilograms per meter squared (kg/m\^2) (inclusive). * Male. * Subjects with female partners of child bearing potential must use a condom from the time of first dose of study medication until follow-up. * Capable of giving signed informed consent, which includes compliance with pre-defined requirements and restrictions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) of GSK3191607 in plasma following a single intravenous (IV) microdose | 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 | 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 | 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 | 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) is the area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration. |
| AUC(0-infinity) of GSK3191607 following a single IV microdose | 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) is the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. |
| Systemic clearance (CL) of GSK3191607 following a single IV microdose | 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) | 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 | 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 | RDM is a measure of total radioactivity. Cmax of RDM will be compared with that of the parent drug (GSK3191607). |
| T1/2 of RDM following a single IV microdose of [14C]-GSK3191607 | 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 will be compared with that of the parent drug. |
| Tmax of RDM following a single IV microdose of [14C]-GSK3191607 | 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 will be compared with that of the parent drug. |
| AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607 | 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 will be compared with that of the parent drug. |
| AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607 | 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 will be compared with that of the parent drug. |
| Amount of RDM excreted in urine (Ae) following a single IV microdose of [14C]-GSK3191607 | Pre-dose; and 0-24 hours and 24-48 hours after the start of infusion | Subjects will be asked to void their bladders before study treatment administration. A blank urine sample will be collected pre-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole-Blood:Plasma ratio of Cmax of RDM following a single IV microdose of [14C]-GSK3191607 | 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 RDM in whole blood will be compared with that of RDM in plasma. |
| Whole-Blood:Plasma ratio of tmax of RDM following a single IV microdose of [14C]-GSK3191607 | 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 in whole blood will be compared with that of RDM in plasma. |
| Whole-Blood:Plasma ratio of t1/2 of RDM following a single IV microdose of [14C]-GSK3191607 | 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 in whole blood will be compared with that of RDM in plasma. |
| Whole-Blood:Plasma ratio of AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607 | 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 in whole blood will be compared with that of RDM in plasma. |
| Whole-Blood:Plasma ratio of AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607 | 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 in whole blood will be compared with that of RDM in plasma. |
| Number of subjects with adverse events | Start of infusion until follow-up (up to Day 25) | — |
| Number of subjects with clinically significant abnormal laboratory parameters | Day -1, Day 1, Day 2, and follow-up (up to Day 25) | Hematology, clinical chemistry, and urinalysis parameters will be evaluated. |
| Number of subjects with clinically significant abnormal 12-lead electrocardiogram (ECG) parameters | Pre-dose, Day 1, Day 2, and follow-up (up to Day 25) | 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. |
| Number of subjects with clinically significant abnormal vital signs parameters | Pre-dose, Day 1, Day 2, Day 3, and follow-up (up to Day 25) | 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. |
Countries
United Kingdom
Outcome results
None listed