Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
AUC(0-inf) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-inf) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-inf) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-inf) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as AUC(0-inf) is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
AUC(0-t) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-t) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC (0-t) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-t) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at indicated time points for PK analysis. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Maximum Observed Concentration (Cmax) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Cmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Cmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Cmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Cmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at indicated time points for PK analysis. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Time of Occurrence of Cmax (Tmax) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Tmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Tmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Tmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Tmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at indicated time points for PK analysis. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Terminal Phase Half-life (T1/2) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
T1/2 in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
T1/2 of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
T1/2 in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
T1/2 of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as T1/2 is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. |
Day 1: 2, 4, 6, 8, 10 hours |
|
Primary |
Volume of Distribution at Steady State (Vss) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Clearance (CL) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Renal Clearance (CLr) Following Administration of IV Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative amount [Ae][Urine] for Period 1)/(Plasma AUC[0-inf]). |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
CLr Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative Ae[Urine] for Period 2)/(Plasma AUC[0-inf]). |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Oral Clearance (CL/F) in Plasma Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
CL/F in Plasma Following Administration Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Apparent Volume of Distribution (Vz/F) Following Administration of Oral Dose of GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Vz/F Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Absolute Oral Bioavailability of GSK3640254 |
Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(Oral Tablet)/Dose(Oral Tablet) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses were analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Percentage of Drug Escaping First Pass Hepatic Clearance (Fh) Following Administration of [14C]-GSK3640254 IV |
Blood samples were collected at the indicated time points for PK analysis. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute). |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Percentage of Drug Absorbed (Fa) Following Administration of [14C]-GSK3640254 Oral Suspension |
Blood samples were collected at the indicated time points for PK analysis. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Percentage of Drug Escaping Gut Metabolism (Fg) Following Administration of [14C]-GSK3640254 Oral Suspension |
Blood samples were collected at the indicated time points for PK analysis. Fg is defined as the fraction metabolized by gut wall as a fraction of the oral dose and was expressed as 1 minus Metabolite load following intravenous and oral administration multiplied by 100. |
Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
Primary |
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254 |
Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. Not applicable (NA) indicates that No concentration values detected for pre-dose. |
Day 1 (Pre-dose), 5, 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
|
Primary |
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254 |
Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. |
Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
|
Primary |
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254 |
Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. NA indicates that No concentration values detected for pre-dose. |
Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
|
Primary |
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254 |
Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. |
Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
|
Secondary |
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with common (greater than or equal to [>=]5 percent [%]) non-serious AEs and SAEs is presented. |
Up to 50 days |
|
Secondary |
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline |
Blood samples were collected to analyze following hematology parameters; Basophils, Eosinophils, Erythrocytes mean corpuscular hemoglobin (MCH), Erythrocytes mean corpuscular volume (MCV), Erythrocytes, Hematocrit (HCT), Hemoglobin (Hb), Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes and Reticulocytes/Erythrocytes. Participants were counted in worst case category if their value changed to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.] High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline value=latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. |
Baseline (Day 1: pre-dose) and Up to 50 Days |
|
Secondary |
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline |
Blood samples were collected to analyze following clinical chemistry parameters:Alanine aminotransferase(ALT),albumin,alkaline phosphatase(ALP),aspartate aminotransferase(AST),bilirubin,calcium,chloride,cholesterol,creatinine,direct bilirubin,globulin,glucose,high-density lipoprotein (HDL) cholesterol,low-density lipoprotein (LDL) cholesterol,phosphate,potassium,protein,sodium,triglycerides,urate and urea.Participants were counted in worst case category if their value changed to(low,normal or high),unless there was no change in their category.Participants whose laboratory value category was unchanged(e.g. High to High),or whose value became normal,were recorded in the 'To Normal or No Change' category.Participants were counted twice if the participant had values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline value=latest pre-dose assessment(prior to oral dose) in each treatment period,with a non-missing value,including those from unscheduled visits |
Baseline (Day 1: pre-dose) and Up to 50 Days |
|
Secondary |
Number of Participants With Clinically Significant Urinalysis Findings |
Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and potential of Hydrogen (pH). Number of participants with clinically significant urinalysis findings are presented. |
Up to 50 days |
|
Secondary |
Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings |
12-lead ECGs were recorded with the participants in semi-supine position after 5 minutes rest using an automated ECG machine that measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal, not clinically significant (NCS) and Clinically significant (CS) ECG findings for worst case post-Baseline are presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. |
Baseline (Day 1: pre-dose) and Up to 50 days |
|
Secondary |
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
SBP and DBP were measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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Secondary |
Change From Baseline in Pulse Rate |
Pulse rate was measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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Secondary |
Change From Baseline in Respiratory Rate |
Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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Secondary |
Change From Baseline in Temperature |
Temperature was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Baseline (Day 1: pre-dose), Day 1 (4 hours), 36, 72, 96, 120, 144, 168 hours and Day 8 |
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Secondary |
Change From Baseline in Weight |
Weight was measured and recorded. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Baseline (Day 1: pre-dose) and up to Day 8 |
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Secondary |
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254 |
Blood samples were collected at the indicated time points for analysis of total radioactivity in blood to plasma. It was calculated as Radioactivity Concentration in blood (Cb) divided by Radioactivity Concentration in plasma (Cp). |
Day 1: 2, 4, 6, 8 and 10 hours |
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