Trial Outcomes & Findings for Absorption and Elimination of Radiolabeled Daprodustat (NCT NCT03239522)
NCT ID: NCT03239522
Last Updated: 2019-12-03
Results Overview
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
COMPLETED
PHASE1
6 participants
Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2
2019-12-03
Participant Flow
This study evaluated the excretion balance of daprodustat(GSK1278863) using radiolabeled 14 Carbon \[14C\]-drug substance administered orally, and as an intravenous (IV) infusion, administered as a micro tracer dose (concomitant with an oral, non-radiolabeled dose) in healthy male participants.
Participants were enrolled at a single center in United Kingdom. A total of 6 participants were enrolled in the study. All the enrolled participants were randomized to receive study treatment.
Participant milestones
| Measure |
All Participants Receiving GSK1278863
Participants received a single 6 milligram (mg) oral dose of GSK1278863 on Day 1 of treatment period 1, after an overnight fast of at least 8 hours. After approximately 1 hour, participants received 50 microgram (µg) \[14C\]-GSK1278863 by IV infusion over 1 hour. It was followed by a washout period of 7 days. On Day 1 of treatment period 2, each participant received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours.
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|---|---|
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Treatment Period 1 (Up to 7 Days)
STARTED
|
6
|
|
Treatment Period 1 (Up to 7 Days)
COMPLETED
|
6
|
|
Treatment Period 1 (Up to 7 Days)
NOT COMPLETED
|
0
|
|
Washout Period (Up to 7 Days)
STARTED
|
6
|
|
Washout Period (Up to 7 Days)
COMPLETED
|
6
|
|
Washout Period (Up to 7 Days)
NOT COMPLETED
|
0
|
|
Treatment Period 2 (Up to 15 Days)
STARTED
|
6
|
|
Treatment Period 2 (Up to 15 Days)
COMPLETED
|
6
|
|
Treatment Period 2 (Up to 15 Days)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Absorption and Elimination of Radiolabeled Daprodustat
Baseline characteristics by cohort
| Measure |
All Participants Receiving GSK1278863
n=6 Participants
Participants received a single 6 milligram (mg) oral dose of GSK1278863 on Day 1 of treatment period 1, after an overnight fast of at least 8 hours. After approximately 1 hour, participants received 50 microgram (µg) \[14C\]-GSK1278863 by IV infusion over 1 hour. It was followed by a washout period of 7 days. On Day 1 of treatment period 2, each participant received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours.
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|---|---|
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Age, Continuous
|
40.7 Years
STANDARD_DEVIATION 8.57 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
WHITE - ARABIC/NORTH AFRICAN HERITAGE
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1 Participants
n=5 Participants
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Race/Ethnicity, Customized
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE
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5 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=5 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-Inf]) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863
|
6.6864 Hour*nanogram equivalent per milliliter
Geometric Coefficient of Variation 19.8
|
2278.8914 Hour*nanogram equivalent per milliliter
Geometric Coefficient of Variation 18.2
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). Data were not analyzed for radiolabeled oral dose GSK1278863 as there were not enough data points captured for a terminal slope required to calculate AUC (0-inf).
Blood samples were planned to be collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error. Data were not analyzed for radiolabeled oral dose of GSK1278863 as there were not enough data points captured for a terminal slope required to calculate AUC (0-inf). The blood assay could not detect radiation levels at the time points blood was drawn to go into these calculations.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC [0-t]) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863
|
6.5252 Hour*nanogram equivalent per milliliter
Geometric Coefficient of Variation 18.9
|
2206.7099 Hour*nanogram equivalent per milliliter
Geometric Coefficient of Variation 18.5
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—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation).
Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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AUC (0-t) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863
|
—
|
824.6102 Hour*nanogram equivalent per milliliter
Geometric Coefficient of Variation 17.2
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863
|
3.0114 Nanogram equivalent per milliliter
Geometric Coefficient of Variation 15.8
|
623.9059 Nanogram equivalent per milliliter
Geometric Coefficient of Variation 34.8
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation).
Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Cmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863
|
—
|
289.9998 Nanogram equivalent per milliliter
Geometric Coefficient of Variation 30.7
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863
|
0.9833 Hour
Interval 0.983 to 1.25
|
0.7583 Hour
Interval 0.5 to 3.0
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—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation).
Blood samples were collected from participants at indicated time points after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Tmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863
|
—
|
1.0000 Hour
Interval 1.0 to 3.0
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—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=5 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
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|---|---|---|---|
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Apparent Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863
|
6.7699 Hour
Geometric Coefficient of Variation 106.4
|
61.8251 Hour
Geometric Coefficient of Variation 15.1
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). Data were not analyzed for radiolabeled oral dose GSK1278863 as there were not enough data points captured for a terminal slope required to calculate t1/2.
Blood samples were planned to be collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error. Data were not analyzed for radiolabeled oral dose of GSK1278863 as there were not enough data points captured for a terminal slope required to calculate t1/2. The blood assay could not detect radiation levels at the time points blood was drawn to go into these calculations.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points in treatment period 1, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=5 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Volume of Distribution at Steady State (Vss) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863
|
32.2355 Liters
Geometric Coefficient of Variation 59.1
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation).
Blood samples were planned to be collected from participants at indicated time points in treatment period 1, after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points in treatment period 1 after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=5 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Total Systemic Clearance (CL) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863
|
7.4779 Liters per hour
Geometric Coefficient of Variation 19.8
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation).
Blood samples were planned to be collected from participants at indicated time points in treatment period 1 after administration of study treatment to investigate the pharmacokinetics of GSK1278863 in blood. Data were not collected for blood total radioactivity concentration following administration of radiolabeled IV dose of GSK1278863 because of an error (deviation). The deviation is due to a processing error: labels for whole blood draws, and aliquots for shipment were not generated in error.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose and then over 24 hours collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120,120-144 and 144-168 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Urine samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in urine. All participants were asked to void their bladders before study treatment administration.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
Pre-dose; n=6
|
0.000 Percent dose excreted
Standard Deviation 0.0000
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
0-24 hours; n=6
|
20.450 Percent dose excreted
Standard Deviation 2.7441
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
24-48 hours; n=6
|
20.838 Percent dose excreted
Standard Deviation 2.8280
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
48-72 hours; n=6
|
21.003 Percent dose excreted
Standard Deviation 2.8723
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
72-96 hours; n=6
|
21.065 Percent dose excreted
Standard Deviation 2.8744
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
96-120 hours; n=6
|
21.065 Percent dose excreted
Standard Deviation 2.8744
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
120-144 hours; n=6
|
21.065 Percent dose excreted
Standard Deviation 2.8744
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863
144-168 hours; n=5
|
21.434 Percent dose excreted
Standard Deviation 3.0507
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and then over 24 hour collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Fecal samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in feces.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
Pre-dose; n=6
|
0.000 Percent dose excreted
Standard Deviation 0.0000
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
0-24 hours; n=5
|
0.096 Percent dose excreted
Standard Deviation 0.1292
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
24-48 hours; n=5
|
22.298 Percent dose excreted
Standard Deviation 31.0164
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
48-72 hours; n=6
|
49.988 Percent dose excreted
Standard Deviation 25.3857
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
72-96 hours; n=6
|
68.312 Percent dose excreted
Standard Deviation 6.0872
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
96-120 hours; n=5
|
73.450 Percent dose excreted
Standard Deviation 3.1046
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
120-144 hours; n=5
|
74.698 Percent dose excreted
Standard Deviation 2.1027
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863
144-168 hours; n=4
|
73.553 Percent dose excreted
Standard Deviation 3.6611
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and then over 24 hour collection periods as follows: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Urine and fecal samples were collected at the indicated time points to determine the rate and extent of cumulative excretion of total radioactivity in urine and feces.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
Pre-dose; n=6
|
0.000 Percent dose excreted
Standard Deviation 0.0000
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
0-24 hours; n=6
|
20.530 Percent dose excreted
Standard Deviation 2.7223
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
24-48 hours; n=6
|
39.433 Percent dose excreted
Standard Deviation 28.2968
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
48-72 hours; n=6
|
70.992 Percent dose excreted
Standard Deviation 25.9980
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
72-96 hours; n=6
|
89.377 Percent dose excreted
Standard Deviation 6.3351
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
96-120 hours; n=6
|
94.177 Percent dose excreted
Standard Deviation 2.1428
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
120-144 hours; n=6
|
94.705 Percent dose excreted
Standard Deviation 2.0982
|
—
|
—
|
|
Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time
144-168 hours; n=5
|
94.582 Percent dose excreted
Standard Deviation 2.3066
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=3 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
AUC (0-Inf) of GSK1278863 in Plasma Following Administration IV and Both Oral Doses
|
199.2552 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.9
|
2.6509 Hour*nanogram per milliliter
Geometric Coefficient of Variation 27.4
|
940.2011 Hour*nanogram per milliliter
Geometric Coefficient of Variation 28.6
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
AUC(0-t) of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses
|
198.1658 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.8
|
2.6368 Hour*nanogram per milliliter
Geometric Coefficient of Variation 20.4
|
938.5541 Hour*nanogram per milliliter
Geometric Coefficient of Variation 28.7
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Cmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses
|
96.1190 Nanogram per milliliter
Geometric Coefficient of Variation 17.2
|
2.0058 Nanogram per milliliter
Geometric Coefficient of Variation 25.5
|
544.7022 Nanogram per milliliter
Geometric Coefficient of Variation 34.1
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population
Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Tmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses
|
2.1167 Hour
Interval 1.417 to 4.0
|
0.983 Hour
Interval 0.983 to 0.983
|
0.5000 Hour
Interval 0.5 to 0.517
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points, after administration of IV dose, both radiolabeled and non-radiolabeled oral doses of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=3 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
T1/2 of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses
|
1.8786 Hour
Geometric Coefficient of Variation 21.6
|
2.0653 Hour
Geometric Coefficient of Variation 6.6
|
2.5037 Hour
Geometric Coefficient of Variation 30.2
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863.Pharmacokinetic analysis was conducted using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2391220; n=6,0,5
|
33.7699 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.1
|
—
|
139.7713 Hour*nanogram per milliliter
Geometric Coefficient of Variation 19.0
|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2487818; n=6,0,6
|
21.7209 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.3
|
—
|
92.0554 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.7
|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506102; n=6,0,6
|
8.6207 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.5
|
—
|
33.1332 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.6
|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506104; n=6,0,5
|
34.1180 Hour*nanogram per milliliter
Geometric Coefficient of Variation 11.9
|
—
|
140.3785 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.7
|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531398; n=6,0,6
|
15.0285 Hour*nanogram per milliliter
Geometric Coefficient of Variation 13.1
|
—
|
61.7760 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.4
|
|
AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531401; n=6,0,6
|
34.4699 Hour*nanogram per milliliter
Geometric Coefficient of Variation 21.9
|
—
|
124.1320 Hour*nanogram per milliliter
Geometric Coefficient of Variation 25.5
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2391220
|
32.2574 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.0
|
—
|
142.2907 Hour*nanogram per milliliter
Geometric Coefficient of Variation 18.9
|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2487818
|
21.2933 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.8
|
—
|
90.9953 Hour*nanogram per milliliter
Geometric Coefficient of Variation 16.7
|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506102
|
8.0798 Hour*nanogram per milliliter
Geometric Coefficient of Variation 14.1
|
—
|
31.8897 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.9
|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506104
|
32.3120 Hour*nanogram per milliliter
Geometric Coefficient of Variation 11.9
|
—
|
142.3372 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.6
|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531398
|
14.4743 Hour*nanogram per milliliter
Geometric Coefficient of Variation 13.4
|
—
|
60.2615 Hour*nanogram per milliliter
Geometric Coefficient of Variation 15.5
|
|
AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531401
|
31.7836 Hour*nanogram per milliliter
Geometric Coefficient of Variation 18.8
|
—
|
122.7102 Hour*nanogram per milliliter
Geometric Coefficient of Variation 25.8
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population.Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2391220
|
7.5219 Nanogram per milliliter
Geometric Coefficient of Variation 14.4
|
—
|
31.5278 Nanogram per milliliter
Geometric Coefficient of Variation 30.4
|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2487818
|
6.0391 Nanogram per milliliter
Geometric Coefficient of Variation 19.1
|
—
|
25.4542 Nanogram per milliliter
Geometric Coefficient of Variation 33.0
|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506102
|
1.8233 Nanogram per milliliter
Geometric Coefficient of Variation 16.6
|
—
|
6.8139 Nanogram per milliliter
Geometric Coefficient of Variation 25.7
|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506104
|
7.3607 Nanogram per milliliter
Geometric Coefficient of Variation 13.5
|
—
|
30.4258 Nanogram per milliliter
Geometric Coefficient of Variation 27.6
|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531398
|
3.5279 Nanogram per milliliter
Geometric Coefficient of Variation 12.7
|
—
|
13.5590 Nanogram per milliliter
Geometric Coefficient of Variation 25.8
|
|
Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531401
|
6.4247 Nanogram per milliliter
Geometric Coefficient of Variation 23.6
|
—
|
21.9493 Nanogram per milliliter
Geometric Coefficient of Variation 36.8
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2391220
|
3.5000 Hour
Interval 2.983 to 6.0
|
—
|
2.0000 Hour
Interval 1.5 to 4.0
|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2487818
|
3.5000 Hour
Interval 1.983 to 6.0
|
—
|
2.0000 Hour
Interval 1.5 to 4.0
|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506102
|
3.5000 Hour
Interval 2.983 to 6.0
|
—
|
2.0000 Hour
Interval 2.0 to 4.0
|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506104
|
4.0000 Hour
Interval 2.983 to 6.0
|
—
|
2.0000 Hour
Interval 2.0 to 4.0
|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531398
|
3.5000 Hour
Interval 2.983 to 6.0
|
—
|
2.0000 Hour
Interval 2.0 to 4.0
|
|
Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531401
|
4.0000 Hour
Interval 3.0 to 6.0
|
—
|
2.0000 Hour
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 2Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were collected from participants at indicated time points, for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2391220; n=6,0, 5
|
1.9805 Hour
Geometric Coefficient of Variation 7.9
|
—
|
3.1506 Hour
Geometric Coefficient of Variation 26.1
|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2487818; n=6,0, 6
|
1.5744 Hour
Geometric Coefficient of Variation 12.5
|
—
|
1.8644 Hour
Geometric Coefficient of Variation 10.7
|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506102; n=6,0, 6
|
2.0037 Hour
Geometric Coefficient of Variation 15.9
|
—
|
2.2738 Hour
Geometric Coefficient of Variation 5.1
|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2506104; n=6,0, 5
|
2.0849 Hour
Geometric Coefficient of Variation 8.0
|
—
|
3.3870 Hour
Geometric Coefficient of Variation 10.9
|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531398; n=6,0, 6
|
1.7006 Hour
Geometric Coefficient of Variation 14.7
|
—
|
1.9767 Hour
Geometric Coefficient of Variation 3.8
|
|
T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses
GSK2531401; n=6,0, 6
|
2.3217 Hour
Geometric Coefficient of Variation 12.0
|
—
|
2.9197 Hour
Geometric Coefficient of Variation 9.9
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=3 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Vss of GSK1278863 in Plasma Following IV Dose Administration
|
14.3387 Liter
Geometric Coefficient of Variation 23.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were planned to be collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Plasma samples were collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 to investigate the pharmacokinetics of GSK1278863 in plasma. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=3 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
CL of GSK1278863 in Plasma Following IV Dose Administration
|
18.8612 Liter per hour
Geometric Coefficient of Variation 27.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Plasma samples were planned to be collected from participants at indicated time points, after administration of radiolabeled IV dose of GSK1278863 for metabolite profiling. GSK2391220, GSK2506104, GSK2487818, GSK2506102, GSK2531398 and GSK2531401 were metabolites of GSK1278863. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Data were not collected for GSK1278863 metabolites following IV dose as analysis of pharmacokinetic parameters of only parent compound following IV dose was of interest to calculate the bioavailability and not the metabolites.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose in treatment period 1Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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)/Dose(oral) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses administered in treatment period 1 was analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Absolute Bioavailability of GSK1278863 Following Oral Dosing
AUC (0-inf); n=3
|
0.6575 Ratio of dose normalized AUC
Geometric Coefficient of Variation 11.8
|
—
|
—
|
|
Absolute Bioavailability of GSK1278863 Following Oral Dosing
AUC (0-t); n=6
|
0.6263 Ratio of dose normalized AUC
Geometric Coefficient of Variation 10.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 0-8 hours, 10-12 hours in period 2Population: Pharmacokinetic Population
Blood samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of \[14C\]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220) and M33 combined, M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. 2 pooled plasma samples were prepared. Aliquots of plasma samples collected between 0 to 8 hours post-dose from each participant were pooled in proportion to the time intervals. An equal amount of the individual pools from each participant was then pooled to create 1 plasma sample that was representative of the mean area under curve over the range of 0-8 hour. The second pool (10-12 hours pool) was obtained by mixing equal volume of the plasma samples at 10 and 12 hour across all participants. Percent radioactivity recovered for each metabolite in plasma following a single oral dose of \[14C\]-GSK1278863 at 25 mg is presented.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M2 (GSK2391220) and M33 combined, 0-8 hours
|
10.4 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M2 (GSK2391220) and M33 combined, 10-12 hours
|
14.4 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M3 (GSK2506104), 0-8 hours
|
7.6 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M3 (GSK2506104), 10-12 hours
|
11.8 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M4 (GSK2487818), 0-8 hours
|
5.7 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M4 (GSK2487818), 10-12 hours
|
NA Percent radioactivity
Data is not available since concentration of metabolite was not detected in the sample.
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M6 (GSK2531398), 0-8 hours
|
3.6 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M6 (GSK2531398), 10-12 hours
|
NA Percent radioactivity
Data is not available as all concentration values were less than the lower limit of quantification.
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M13 (GSK2531401), 0-8 hours
|
8.3 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M13 (GSK2531401), 10-12 hours
|
16.1 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M5 (GSK2506102) and M14 combined, 0-8 hours
|
4.5 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M5 (GSK2506102) and M14 combined, 10-12 hours
|
NA Percent radioactivity
Data is not available as all concentration values were less than the lower limit of quantification.
|
—
|
—
|
SECONDARY outcome
Timeframe: 0-24 hours in period 2Population: Pharmacokinetic Population
Urine samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of \[14C\]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220) and M33 combined, M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. One pooled urine sample was prepared by urine collected from 0 to 24 hours post dose from all participants. Percent radioactivity recovered for each metabolite in urine following a single oral dose of \[14C\]-GSK1278863 at 25 mg is presented.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M2 (GSK2391220) and M33 combined
|
15.8 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M3 (GSK2506104)
|
16.0 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M4 (GSK2487818)
|
7.9 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M6 (GSK2531398)
|
5.8 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M13 (GSK2531401)
|
16.5 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M5 (GSK2506102) and M14 combined
|
10.4 Percent radioactivity
|
—
|
—
|
SECONDARY outcome
Timeframe: 0-120 hours in period 2Population: Pharmacokinetic Population
Feces samples were collected in treatment period 2 to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single oral dose of \[14C\]-GSK1278863 at 25 mg. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220), M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102) and M14 combined. One pooled feces sample was prepared by samples collected from 0 to 120 hours post dose from all participants. Percent radioactivity recovered for each metabolite in feces following a single oral dose of \[14C\]-GSK1278863 at 25 mg is presented.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M2 (GSK2391220)
|
19.8 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M3 (GSK2506104)
|
14.1 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M4 (GSK2487818)
|
17.0 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M6 (GSK2531398)
|
6.2 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M13 (GSK2531401)
|
4.9 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg
M5 (GSK2506102) and M14 combined
|
7.7 Percent radioactivity
|
—
|
—
|
SECONDARY outcome
Timeframe: 3 hours post-oral dose in period 1Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
The bile string was swallowed by participants prior to oral dose and was removed 3 hours after the oral dose (1 hour after the end of the IV infusion) in treatment period-1. Duodenal bile string extracts were pooled to create a single pool sample to measure total radioactivity and to characterize the metabolite profiling of GSK1278863 following a single dose of \[14C\]-GSK1278863 50 µg IV infusion. Potential metabolites were M3 (GSK2506104), M2 (GSK2391220), M4 (GSK2487818), M6 (GSK2531398), M13 (GSK2531401), M5 (GSK2506102). Mean percent radioactivity recovered for each metabolite in bile following a single dose of \[14C\]-GSK1278863 50 µg IV infusion is presented.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=3 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M2 (GSK2391220)
|
12.3 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M3 (GSK2506104)
|
20.0 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M4 (GSK2487818)
|
15.5 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M6 (GSK2531398)
|
6.3 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M13 (GSK2531401)
|
2.4 Percent radioactivity
|
—
|
—
|
|
Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion
M5
|
11.1 Percent radioactivity
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 43 daysPopulation: Safety Population
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose which 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, associated with liver injury and impaired liver function or any other situations as per Medical or scientific judgment. Safety Population comprised of all participants who take at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Any AE
|
2 Participants
|
2 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 43 daysPopulation: Safety Population
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Severity was categorized as mild, moderate and severe. The number of participants with AEs at any type of severity (mild, moderate and severe) has been presented.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With AEs at a Particular Severity
Moderate
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With AEs at a Particular Severity
Mild
|
2 Participants
|
2 Participants
|
—
|
|
Number of Participants With AEs at a Particular Severity
Severe
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 43 daysPopulation: Safety Population
Blood samples were collected from participants at indicated time points for the analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Alkaline phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Potassium, Protein, Sodium and Urea. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (example given \[e.g.\], High to High), or whose value became normal, are 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%. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Urea; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
ALT; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
ALT;To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
ALT; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Alk Phos; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Alk Phos; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Alk Phos; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
AST; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
AST;To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
AST; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Bilirubin; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Bilirubin; To Normal or No Change
|
5 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Bilirubin; To High
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Calcium; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Calcium; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Calcium; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Creatinine; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Creatinine; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Creatinine; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Direct Bilirubin; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Direct Bilirubin; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Direct Bilirubin; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Glucose; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Glucose; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Glucose; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Potassium; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Potassium; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Potassium; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Protein; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Protein; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Protein; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Sodium; To Low
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Sodium; To Normal or No Change
|
5 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Sodium; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Urea;To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range
Urea; To High
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 43 daysPopulation: Safety Population
Blood samples were collected from participants at indicated time points for the analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes, and Reticulocytes/Erythrocytes. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are 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%. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Leukocytes; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Leukocytes; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Leukocytes; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Lymphocytes; To Low
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Lymphocytes; To Normal or No Change
|
5 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Lymphocytes; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Monocytes; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Monocytes; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Monocytes; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Neutrophils; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Neutrophils; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Neutrophils; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Platelets; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Platelets; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Platelets; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes; To High
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes/Erythrocytes; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes/Erythrocytes; To Normal or No Change
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Reticulocytes/Erythrocytes; To High
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Basophils; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Basophils; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Basophils; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Eosinophils; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Eosinophils; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Eosinophils; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCH; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCH; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCH; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCV; To Low
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCV; To Normal or No Change
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
MCV; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Erythrocytes; To Low
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Erythrocytes; To Normal or No Change
|
5 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Erythrocytes; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hematocrit; To Low
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hematocrit; To Normal or No Change
|
5 Participants
|
5 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hematocrit; To High
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hemoglobin; To Low
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hemoglobin; To Normal or No Change
|
5 Participants
|
6 Participants
|
—
|
|
Number of Participants With Worst Case Hematology Results Relative to Normal Range
Hemoglobin; To High
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 43 daysPopulation: Safety Population
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including specific gravity and PH of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase in urine.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With Abnormal Urinalysis Findings
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (on Day 1) and Day 8 in treatment period 2; 144 hours (Day 7) in treatment period 1Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Full 12-lead ECGs were recorded with the participant in a supine position. The number of participants with abnormal ECG findings at indicated time points were presented. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Pre-dose (Day 1); n=0,6
|
—
|
0 Participants
|
—
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
144 hours (Day 7); n= 6, 0
|
0 Participants
|
—
|
—
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 8; n=0, 6
|
—
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (average of Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Vital sign including systolic and diastolic blood pressure were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the mean of the 3 pre-dose measurements (Average \[Avg\] Pre-dose) taken on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Change From Baseline in Blood Pressure
SBP; Avg 3 hours; n=6, 6
|
-0.17 Millimeters of mercury
Standard Deviation 5.722
|
-1.22 Millimeters of mercury
Standard Deviation 3.468
|
—
|
|
Change From Baseline in Blood Pressure
SBP; Avg 144 hours (Day 7); n=6, 6
|
5.06 Millimeters of mercury
Standard Deviation 10.521
|
-2.00 Millimeters of mercury
Standard Deviation 9.541
|
—
|
|
Change From Baseline in Blood Pressure
SBP; Avg Day 8; n=0,6
|
—
|
4.22 Millimeters of mercury
Standard Deviation 4.075
|
—
|
|
Change From Baseline in Blood Pressure
DBP; Avg 3 hours; n=6, 6
|
1.22 Millimeters of mercury
Standard Deviation 5.484
|
0.89 Millimeters of mercury
Standard Deviation 4.834
|
—
|
|
Change From Baseline in Blood Pressure
DBP; Avg 144 hours (Day 7); n=6, 6
|
3.61 Millimeters of mercury
Standard Deviation 9.365
|
-1.00 Millimeters of mercury
Standard Deviation 9.814
|
—
|
|
Change From Baseline in Blood Pressure
DBP; Avg Day 8; n=0,6
|
—
|
3.39 Millimeters of mercury
Standard Deviation 5.170
|
—
|
SECONDARY outcome
Timeframe: Baseline (average of Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Heart rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the mean of the 3 pre-dose measurements (Avg Pre-dose) taken on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Change From Baseline in Heart Rate
Avg 3 hours; n=6, 6
|
0.22 Beats per minute
Standard Deviation 3.526
|
1.67 Beats per minute
Standard Deviation 3.425
|
—
|
|
Change From Baseline in Heart Rate
Avg 144 hours (Day 7); n=6, 6
|
1.28 Beats per minute
Standard Deviation 6.571
|
3.78 Beats per minute
Standard Deviation 5.500
|
—
|
|
Change From Baseline in Heart Rate
Avg Day 8; n=0,6
|
—
|
4.72 Beats per minute
Standard Deviation 5.535
|
—
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Respiratory rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the pre-dose on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Change From Baseline in Respiratory Rate
3 hours; n=6, 6
|
-0.67 Breaths per minute
Standard Deviation 2.422
|
-0.33 Breaths per minute
Standard Deviation 4.082
|
—
|
|
Change From Baseline in Respiratory Rate
144 hours (Day 7); n=6, 6
|
-1.33 Breaths per minute
Standard Deviation 2.066
|
-0.33 Breaths per minute
Standard Deviation 1.506
|
—
|
|
Change From Baseline in Respiratory Rate
Day 8; n=0,6
|
—
|
0.00 Breaths per minute
Standard Deviation 2.530
|
—
|
SECONDARY outcome
Timeframe: Baseline (Pre-dose on Day 1 in treatment period 1 and 2); 3 hours, 144 hours (Day 7) in treatment period 1; 3 hours, 144 hours (Day 7) and Day 8 in treatment period 2Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Body temperature measurement was performed in participants at indicated time points. Baseline is defined as the pre-dose on Day 1 in each treatment period. Change from Baseline was defined as any visit value minus the Baseline value. Data has been presented for participants with respect to the actual treatment received in respective treatment periods.
Outcome measures
| Measure |
[14C]-GSK1278863 50 µg IV Infusion
n=6 Participants
Participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour in treatment period 1, after approximately 1 hour of receiving GSK1278863 6 mg Oral tablet.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 Participants
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
[14C]-GSK1278863 25 mg Oral Solution
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|---|
|
Change From Baseline in Body Temperature
3 hours; n=6, 6
|
0.08 Celsius
Standard Deviation 0.183
|
0.25 Celsius
Standard Deviation 0.455
|
—
|
|
Change From Baseline in Body Temperature
144 hours (Day 7); n=6, 6
|
0.07 Celsius
Standard Deviation 0.446
|
0.12 Celsius
Standard Deviation 0.588
|
—
|
|
Change From Baseline in Body Temperature
Day 8; n=0,6
|
—
|
0.30 Celsius
Standard Deviation 0.693
|
—
|
Adverse Events
GSK1278863 6 mg Oral Tablet+[14C]-GSK1278863 50 µg IV Infusion
[14C]-GSK1278863 25 mg Oral Solution
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
GSK1278863 6 mg Oral Tablet+[14C]-GSK1278863 50 µg IV Infusion
n=6 participants at risk
Participants received a single 6 mg oral dose of GSK1278863 on Day 1 of treatment period 1, after an overnight fast of at least 8 hours. After approximately 1 hour, participants received 50 µg \[14C\]-GSK1278863 by IV infusion over 1 hour.
|
[14C]-GSK1278863 25 mg Oral Solution
n=6 participants at risk
Participants received 25 mg \[14C\]-GSK1278863 as an oral solution, after an overnight fast of at least 8 hours in treatment period 2.
|
|---|---|---|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
16.7%
1/6 • Number of events 2 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
0.00%
0/6 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
0.00%
0/6 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
0.00%
0/6 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 dose of study treatment
|
16.7%
1/6 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 43 days.
SAEs and Non-SAEs were reported by treatment for the Safety Population which comprised of all participants who had taken at least 1 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