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| Name | Class |
|---|---|
| Hammersmith Medicines Research | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [14C]-GSK3191607 IV Microdose | Experimental | Subjects will receive a single microdose of 100 micrograms (mcg) of [14C]-GSK3191607 by intravenous infusion over 15 minutes on Day 1 of the study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]-GSK3191607 | Drug | [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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | AUC(0-t) is the area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration. | 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. | 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 | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
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| Label | URL |
|---|---|
| Results for study 204853 can be found on the GSK Clinical Study Register. | View source |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| 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). | 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. | 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. | 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. | 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. | 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. | Pre-dose; and 0-24 hours and 24-48 hours after the start of infusion |
Tmax of RDM in whole blood will be compared with that of RDM in plasma. |
| 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. | 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. | 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. | 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 | Start of infusion until follow-up (up to Day 25) |
| Number of subjects with clinically significant abnormal laboratory parameters | Hematology, clinical chemistry, and urinalysis parameters will be evaluated. | 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. | 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. | Pre-dose, Day 1, Day 2, Day 3, and follow-up (up to Day 25) |
| D000079426 |
| Vector Borne Diseases |