Trial Outcomes & Findings for Pharmacokinetics and Metabolism of 14 Carbon [14C]-GSK3640254 (NCT NCT04507321)
NCT ID: NCT04507321
Last Updated: 2022-01-31
Results Overview
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
COMPLETED
PHASE1
5 participants
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
2022-01-31
Participant Flow
This was an open-label, non-randomized, 2-period, single-sequence study to determine the pharmacokinetics, balance/excretion, and metabolism of radiolabeled \[14C\]-GSK3640254 following a single intravenous radiolabeled microtracer dose and a single oral radiolabeled dose. The study was conducted at a single center in the United Kingdom.
A total of 5 participants were enrolled in the study. The washout time between dosing in consecutive study periods was at least 13 days.
Participant milestones
| Measure |
GSK3640254 Tablet+[14C]-GSK3640254 IV/ [14C]-GSK3640254 Oral Suspension
Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of \[14C\]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. In Treatment Period 2 on Day 1, participants were administered a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal. The treatment periods were separated by a washout period of at least 13 days between oral doses.
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|---|---|
|
Treatment Period 1 (8 Days)
STARTED
|
5
|
|
Treatment Period 1 (8 Days)
COMPLETED
|
5
|
|
Treatment Period 1 (8 Days)
NOT COMPLETED
|
0
|
|
Treatment Period 2 (8 Days)
STARTED
|
5
|
|
Treatment Period 2 (8 Days)
COMPLETED
|
5
|
|
Treatment Period 2 (8 Days)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics and Metabolism of 14 Carbon [14C]-GSK3640254
Baseline characteristics by cohort
| Measure |
GSK3640254 Tablet+[14C]-GSK3640254 IV/ [14C]-GSK3640254 Oral Suspension
n=5 Participants
Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of \[14C\]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. In Treatment Period 2 on Day 1, participants were administered a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal. The treatment periods were separated by a washout period of at least 13 days between oral doses.
|
|---|---|
|
Age, Continuous
|
37.4 Years
STANDARD_DEVIATION 5.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian- Central/South Asian Heritage
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White- White/Caucasian/European Heritage
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population comprised of all participants in the Safety Population (all participants who took atleast one dose of study intervention) who had at least 1 non-missing PK assessment.
Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
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
|
41234.1841 Hours*nanogram per milliliter
Geometric Coefficient of Variation 14.5
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254
|
NA Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation NA
Not applicable (NA) indicates data was not collected for this outcome measure as it was incorrectly stated as one of the Primary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to parent analyte specifically for blood 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
96.5532 Hours*nanogram per milliliter
Geometric Coefficient of Variation 19.7
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
105.0882 Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation 19.1
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
19026.4818 Hours*nanogram per milliliter
Geometric Coefficient of Variation 21.8
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
23226.8511 Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation 20.7
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254
|
NA Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation NA
NA indicates 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) in Plasma Following Administration of Oral Dose of GSK3640254
|
40816.9451 Hours*nanogram per milliliter
Geometric Coefficient of Variation 14.2
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254
|
NA Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation NA
NA indicates data was not collected for this outcome measure as it was incorrectly stated as one of the Primary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to parent analyte specifically for blood 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-t) in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
93.3371 Hours*nanogram per milliliter
Geometric Coefficient of Variation 20.4
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-t) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
101.8025 Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation 19.4
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC (0-t) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
18828.0326 Hours*nanogram per milliliter
Geometric Coefficient of Variation 21.7
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-t) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
22746.1486 Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation 20.4
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK population
Blood samples were collected at indicated time points for PK analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254
|
2395.2833 Hours*nanogram Equivalent per milliliter
Geometric Coefficient of Variation 17.7
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) in Plasma Following Administration of Oral Dose of GSK3640254
|
1293.0 Nanogram per milliliter
Geometric Coefficient of Variation 7.6
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254
|
NA Nanogram Equivalent per milliliter
Geometric Coefficient of Variation NA
NA indicates data was not collected for this outcome measure as it was incorrectly stated as one of the Primary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to parent analyte specifically for blood 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
8.435 Nanogram per milliliter
Geometric Coefficient of Variation 12.0
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
7.462 Nanogram Equivalent per milliliter
Geometric Coefficient of Variation 6.9
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
628.2 Nanogram per milliliter
Geometric Coefficient of Variation 15.4
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
675.312 Nanogram Equivalent per milliliter
Geometric Coefficient of Variation 13.6
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population
Blood samples were collected at indicated time points for PK analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254
|
377.5 Nanogram Equivalent per milliliter
Geometric Coefficient of Variation 23.9
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Time of Occurrence of Cmax (Tmax) in Plasma Following Administration of Oral Dose of GSK3640254
|
7.00 Hours
Interval 4.5 to 9.0
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254
|
NA Hours
NA indicates data was not collected for this outcome measure as it was incorrectly stated as one of the Primary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to parent analyte specifically for blood 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
0.983 Hours
Interval 0.983 to 0.983
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
0.983 Hours
Interval 0.983 to 0.983
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
4.00 Hours
Interval 1.5 to 5.5
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
4.0000 Hours
Interval 1.5 to 6.0
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population
Blood samples were collected at indicated time points for PK analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254
|
6.0 Hours
Interval 2.0 to 10.0
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Terminal Phase Half-life (T1/2) in Plasma Following Administration of Oral Dose of GSK3640254
|
24.0860 Hours
Geometric Coefficient of Variation 16.4
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254
|
NA Hours
Geometric Coefficient of Variation NA
NA indicates data was not collected for this outcome measure as it was incorrectly stated as one of the Primary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to parent analyte specifically for blood 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
21.6959 Hours
Geometric Coefficient of Variation 12.6
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
29.7527 Hours
Geometric Coefficient of Variation 11.3
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
24.2493 Hours
Geometric Coefficient of Variation 5.1
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254
|
30.0505 Hours
Geometric Coefficient of Variation 11.4
|
—
|
PRIMARY outcome
Timeframe: Day 1: 2, 4, 6, 8, 10 hoursPopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254
|
NA Hours
Geometric Coefficient of Variation NA
NA indicates 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.
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Volume of Distribution at Steady State (Vss) in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
28.7435 Liters
Geometric Coefficient of Variation 21.9
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Clearance (CL) in Plasma Following Administration of IV Dose of [14C]-GSK3640254
|
1.0357 Liters per hour
Geometric Coefficient of Variation 19.7
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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\[0-inf\]).
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Renal Clearance (CLr) Following Administration of IV Dose of [14C]-GSK3640254
|
0.01992 Liters per hour
Geometric Coefficient of Variation 29.2
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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\[0-inf\]).
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
CLr Following Administration of Oral Dose of [14C]-GSK3640254
|
0.01465 Liters per hour
Geometric Coefficient of Variation 30.1
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Oral Clearance (CL/F) in Plasma Following Administration of Oral Dose of GSK3640254
|
4.8503 Liters per hour
Geometric Coefficient of Variation 14.5
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
CL/F in Plasma Following Administration Oral Dose of [14C]-GSK3640254
|
4.4675 Liters per hour
Geometric Coefficient of Variation 21.8
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) Following Administration of Oral Dose of GSK3640254
|
168.5433 Liters
Geometric Coefficient of Variation 14.0
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Vz/F Following Administration of Oral Dose of [14C]-GSK3640254
|
156.2909 Liters
Geometric Coefficient of Variation 19.0
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Absolute Oral Bioavailability of GSK3640254
AUC (0 to infinity)
|
0.2317 Ratio of dose normalized AUC
Geometric Coefficient of Variation 10.1
|
—
|
|
Absolute Oral Bioavailability of GSK3640254
AUC (0 to t)
|
0.2373 Ratio of dose normalized AUC
Geometric Coefficient of Variation 11.1
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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).
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Drug Escaping First Pass Hepatic Clearance (Fh) Following Administration of [14C]-GSK3640254 IV
|
0.9945 Percentage of drug escaped
Geometric Coefficient of Variation 0.1
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Drug Absorbed (Fa) Following Administration of [14C]-GSK3640254 Oral Suspension
|
0.2595 Percentage of drug absorbed
Geometric Coefficient of Variation 8.9
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Drug Escaping Gut Metabolism (Fg) Following Administration of [14C]-GSK3640254 Oral Suspension
|
0.8980 Percentage of drug escaped
Geometric Coefficient of Variation 5.5
|
—
|
PRIMARY outcome
Timeframe: Day 1 (Pre-dose), 5, 24, 48, 72, 96, 120, 144 and 163 hours post-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
Pre-dose
|
NA Percentage of dose excreted
Standard Deviation NA
No concentration values detected for pre-dose.
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
5 hours
|
0 Percentage of dose excreted
Standard Deviation 0.514
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
24 hours
|
1.1 Percentage of dose excreted
Standard Deviation 0.382
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
48 hours
|
1.61 Percentage of dose excreted
Standard Deviation 0.514
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
72 hours
|
1.76 Percentage of dose excreted
Standard Deviation 0.551
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
96 hours
|
1.82 Percentage of dose excreted
Standard Deviation 0.577
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
120 hours
|
1.84 Percentage of dose excreted
Standard Deviation 0.581
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
144 hours
|
1.85 Percentage of dose excreted
Standard Deviation 0.585
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254
163 hours
|
1.86 Percentage of dose excreted
Standard Deviation 0.589
|
—
|
PRIMARY outcome
Timeframe: Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
144 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
72 hours
|
0.31 Percentage of dose excreted
Standard Deviation 0.08
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
96 hours
|
0.33 Percentage of dose excreted
Standard Deviation 0.11
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
120 hours
|
0.34 Percentage of dose excreted
Standard Deviation 0.12
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
Pre-dose
|
0.00 Percentage of dose excreted
Standard Deviation 0.00
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
24 hours
|
0.14 Percentage of dose excreted
Standard Deviation 0.03
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
48 hours
|
0.26 Percentage of dose excreted
Standard Deviation 0.06
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
168 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
192 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
216 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
240 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
264 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254
288 hours
|
0.35 Percentage of dose excreted
Standard Deviation 0.13
|
—
|
PRIMARY outcome
Timeframe: Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144 and 163 hours post-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
Pre-dose
|
NA Percentage of dose excreted
Standard Deviation NA
No concentration values detected for pre-dose.
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
24 hours
|
0.0855 Percentage of dose excreted
Standard Deviation 0.0690
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
48 hours
|
14.6 Percentage of dose excreted
Standard Deviation 9.40
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
72 hours
|
41.7 Percentage of dose excreted
Standard Deviation 13.2
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
96 hours
|
52.0 Percentage of dose excreted
Standard Deviation 12.1
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
120 hours
|
61.1 Percentage of dose excreted
Standard Deviation 6.67
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
144 hours
|
72.1 Percentage of dose excreted
Standard Deviation 5.76
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254
163 hours
|
73.6 Percentage of dose excreted
Standard Deviation 4.87
|
—
|
PRIMARY outcome
Timeframe: Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dosePopulation: PK Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
Pre-dose
|
0.00 Percentage of dose excreted
Standard Deviation 0.00
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
24 hours
|
0.38 Percentage of dose excreted
Standard Deviation 0.59
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
48 hours
|
37.8 Percentage of dose excreted
Standard Deviation 35.1
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
72 hours
|
62.8 Percentage of dose excreted
Standard Deviation 35.9
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
96 hours
|
71.0 Percentage of dose excreted
Standard Deviation 37.5
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
120 hours
|
81.9 Percentage of dose excreted
Standard Deviation 38.3
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
144 hours
|
86.8 Percentage of dose excreted
Standard Deviation 42.4
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
168 hours
|
89.9 Percentage of dose excreted
Standard Deviation 42.6
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
192 hours
|
90.0 Percentage of dose excreted
Standard Deviation 42.3
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
216 hours
|
90.5 Percentage of dose excreted
Standard Deviation 43.0
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
240 hours
|
90.5 Percentage of dose excreted
Standard Deviation 43.0
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
264 hours
|
90.7 Percentage of dose excreted
Standard Deviation 43.3
|
—
|
|
Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254
288 hours
|
90.8 Percentage of dose excreted
Standard Deviation 43.4
|
—
|
SECONDARY outcome
Timeframe: Up to 50 daysPopulation: Safety Population comprised of all participants who received at least one dose of study intervention.
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
Any Non-serious AEs
|
1 Participants
|
1 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
Any SAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose) and Up to 50 DaysPopulation: Safety Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Basophils, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Basophils, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Basophils, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Eosinophils, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Eosinophils, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Eosinophils, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCH, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCH, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCH, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCV, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCV, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes MCV, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Erythrocytes, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hematocrit, To Low
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hematocrit, To Normal or No Change
|
5 Participants
|
3 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hematocrit, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hemoglobin, To Low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hemoglobin, To Normal or No Change
|
5 Participants
|
4 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Hemoglobin, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Leukocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Leukocytes, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Leukocytes, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Lymphocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Lymphocytes, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Lymphocytes, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Monocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Monocytes, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Monocytes, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Neutrophils, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Neutrophils, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Neutrophils, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Platelets, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Platelets, To Normal or No Change
|
5 Participants
|
4 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Platelets, To High
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes, To Normal or No Change
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes, To High
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes/Erythrocytes, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes/Erythrocytes, To Normal or No Change
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline
Reticulocytes/Erythrocytes, To High
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose) and Up to 50 DaysPopulation: Safety Population
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
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALT, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALT, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALT, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Albumin, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Albumin, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Albumin, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALP, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALP, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
ALP, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
AST, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
AST, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
AST, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Bilirubin, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Bilirubin, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Bilirubin, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Calcium, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Calcium, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Calcium, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Chloride, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Chloride, To Normal or No Change
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Chloride, To High
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Cholesterol, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Cholesterol, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Cholesterol, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Creatinine, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Creatinine, To Normal or No Change
|
3 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Creatinine, To High
|
2 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Direct Bilirubin, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Direct Bilirubin, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Direct Bilirubin, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Globulin, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Globulin, To Normal or No Change
|
5 Participants
|
4 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Globulin, To High
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Glucose, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Glucose, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Glucose, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
HDL Cholesterol, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
HDL Cholesterol, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
HDL Cholesterol, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
LDL Cholesterol, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
LDL Cholesterol, To Normal or No Change
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
LDL Cholesterol, To High
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Phosphate, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Phosphate, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Phosphate, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Potassium, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Potassium, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Potassium, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Protein, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Protein, To Normal or No Change
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Protein, To High
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Sodium, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Sodium, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Sodium, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Triglycerides, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Triglycerides, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Triglycerides, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urate, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urate, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urate, To High
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urea, To Low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urea, To Normal or No Change
|
5 Participants
|
5 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline
Urea, To High
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 50 daysPopulation: Safety Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Number of Participants With Clinically Significant Urinalysis Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose) and Up to 50 daysPopulation: Safety Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings
Abnormal, NCS
|
2 Participants
|
3 Participants
|
|
Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings
Abnormal, CS
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP: Day 1 (4 hours); n= 5, 4
|
3.4 Millimeters of mercury (mmHg)
Standard Deviation 6.95
|
-0.3 Millimeters of mercury (mmHg)
Standard Deviation 5.38
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP: Day 1 (4 hours); n = 5, 4
|
2.6 Millimeters of mercury (mmHg)
Standard Deviation 6.19
|
3.0 Millimeters of mercury (mmHg)
Standard Deviation 3.37
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP: Day 8; n= 5, 5
|
2.8 Millimeters of mercury (mmHg)
Standard Deviation 5.07
|
3.0 Millimeters of mercury (mmHg)
Standard Deviation 6.82
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP: Day 8; n= 5, 5
|
2.8 Millimeters of mercury (mmHg)
Standard Deviation 6.30
|
-5.8 Millimeters of mercury (mmHg)
Standard Deviation 6.98
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Change From Baseline in Pulse Rate
Pulse rate: Day 1 (4 hours); n= 5, 4
|
-3.8 Beats per minute
Standard Deviation 7.53
|
-2.3 Beats per minute
Standard Deviation 2.22
|
|
Change From Baseline in Pulse Rate
Pulse rate: Day 8; n= 5, 5
|
8.2 Beats per minute
Standard Deviation 7.19
|
0.0 Beats per minute
Standard Deviation 5.29
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Change From Baseline in Respiratory Rate
Respiratory rate: Day 1 (4 hours); n= 5, 4
|
0.0 Breaths per minute
Standard Deviation 2.83
|
-1.0 Breaths per minute
Standard Deviation 1.15
|
|
Change From Baseline in Respiratory Rate
Respiratory rate: Day 8; n= 5, 5
|
0.8 Breaths per minute
Standard Deviation 1.79
|
0.8 Breaths per minute
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose), Day 1 (4 hours), 36, 72, 96, 120, 144, 168 hours and Day 8Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Change From Baseline in Temperature
Temperature: 4 hours; n= 5, 4
|
0.28 Degree Celsius
Standard Deviation 0.259
|
0.38 Degree Celsius
Standard Deviation 0.403
|
|
Change From Baseline in Temperature
Temperature: 36 hours; n= 5, 5
|
0.04 Degree Celsius
Standard Deviation 0.404
|
0.28 Degree Celsius
Standard Deviation 0.383
|
|
Change From Baseline in Temperature
Temperature: 72 hours; n= 5, 5
|
0.24 Degree Celsius
Standard Deviation 0.336
|
0.32 Degree Celsius
Standard Deviation 0.415
|
|
Change From Baseline in Temperature
Temperature: 96 hours; n= 5, 5
|
0.32 Degree Celsius
Standard Deviation 0.421
|
0.08 Degree Celsius
Standard Deviation 0.363
|
|
Change From Baseline in Temperature
Temperature: 120 hours; n= 5, 5
|
0.26 Degree Celsius
Standard Deviation 0.321
|
-0.14 Degree Celsius
Standard Deviation 0.329
|
|
Change From Baseline in Temperature
Temperature: 144 hours; n= 5, 5
|
0.08 Degree Celsius
Standard Deviation 0.356
|
0.00 Degree Celsius
Standard Deviation 0.430
|
|
Change From Baseline in Temperature
Temperature: 168 hours; n= 5, 5
|
0.12 Degree Celsius
Standard Deviation 0.277
|
0.08 Degree Celsius
Standard Deviation 0.492
|
|
Change From Baseline in Temperature
Temperature: Day 8; n= 5, 5
|
0.36 Degree Celsius
Standard Deviation 0.385
|
0.16 Degree Celsius
Standard Deviation 0.270
|
SECONDARY outcome
Timeframe: Baseline (Day 1: pre-dose) and up to Day 8Population: Safety Population
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.
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
n=5 Participants
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Change From Baseline in Weight
|
-0.64 Kilograms
Standard Deviation 0.792
|
-1.10 Kilograms
Standard Deviation 0.892
|
SECONDARY outcome
Timeframe: Day 1: 2, 4, 6, 8 and 10 hoursPopulation: PK Population
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).
Outcome measures
| Measure |
GSK3640254 Tablet
n=5 Participants
Eligible participants received a single oral dose of 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal on Day 1 in treatment Period 1
|
[14C]-GSK3640254 Oral Suspension
Eligible participants received a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal on Day 1 in treatment period 2.
|
|---|---|---|
|
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254
2 hours
|
0.555 Ratio
Standard Deviation 0.0340
|
—
|
|
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254
4 hours
|
0.480 Ratio
Standard Deviation 0.0844
|
—
|
|
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254
6 hours
|
0.522 Ratio
Standard Deviation 0.0429
|
—
|
|
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254
8 hours
|
0.503 Ratio
Standard Deviation 0.0249
|
—
|
|
Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254
10 hours
|
0.595 Ratio
Standard Deviation 0.164
|
—
|
Adverse Events
GSK3640254 Tablet+[14C]-GSK3640254 IV
[14C]-GSK3640254 Oral Suspension
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
GSK3640254 Tablet+[14C]-GSK3640254 IV
n=5 participants at risk
Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of \[14C\]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. The treatment periods were separated by a washout period of at least 13 days between oral doses.
|
[14C]-GSK3640254 Oral Suspension
n=5 participants at risk
Participants were administered a single oral dose of 85 mg \[14C\]-GSK3640254 as an oral suspension with a moderate fat meal in Treatment Period 2 on Day 1. The treatment periods were separated by a washout period of at least 13 days between oral doses.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • Number of events 1 • All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.
SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment.
|
0.00%
0/5 • All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.
SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment.
|
|
General disorders
Asthenia
|
20.0%
1/5 • Number of events 1 • All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.
SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment.
|
20.0%
1/5 • Number of events 1 • All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.
SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER