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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001729-42 | EudraCT Number |
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Absorption, metabolism and excretion of daprodustat (GSK1278863) have been studied in previous clinical trials; however, the elimination routes and metabolic pathways of daprodustat have not been fully elucidated in humans. This is an open-label, single-center, non-randomized, 2-period, single-sequence, crossover, mass balance study in 6 healthy male participants. The aim of the study is to assess the excretion balance of daprodustat using [14C]-radiolabeled drug substance administered orally, and as an intravenous (IV) infusion, administered as a microtracer dose (concomitant with an oral, non-radiolabeled dose). Absolute bioavailability of an oral dose will also be assessed. Each participant will be involved in the study for up to 10 weeks which include a screening visit, two treatment periods (treatment periods 1 and 2), separated by about 7 days (at least 14 days between oral doses), and a follow up visit 1-2 weeks after the last assessment in treatment period 2. The primary objective of the study is to gain a better understanding of the compound's excretory and metabolic profile. This study will include sampling of duodenal bile to conduct qualitative assessment of drug metabolites in this matrix in order to characterize biliary elimination pathways.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All participants receiving treatment | Experimental | Each participant will receive a single 6 milligram (mg) oral dose of daprodustat on Day 1 of period 1. After approximately 1 hour, participants will receive 50 microgram (µg) of [14C]-GSK1278863 by IV infusion over 1 hour. On Day 1 of period 2, each participant will receive 25 mg [14C]-GSK1278863 as an oral solution. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]-GSK1278863 solution for IV infusion | Drug | It is a clear, colorless solution free from visible particulate matter. Participants will receive 10 mL of 5 µg/mL of [14C]-GSK1278863 IV solution (total dose: 50 µg) by IV infusion over 1 hour. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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). | 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 |
| AUC (0-Inf) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-Inf) of GSK1278863 in Plasma Following Administration IV and Both Oral Doses | 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
Only male participants, aged 30 to 55 years (inclusive) will be enrolled into the study.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Up to 7 Days) |
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| Washout Period (Up to 7 Days) |
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| Treatment Period 2 (Up to 15 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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). | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram equivalent per milliliter | 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 |
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK1278863 6 mg Oral Tablet+[14C]-GSK1278863 50 µg IV Infusion | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 1, 2017 | Jul 27, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 30, 2018 | Jul 27, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000740 | Anemia |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D007262 | Infusions, Intravenous |
| C000599718 | GSK1278863 |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D061605 | Administration, Intravenous |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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| [14C]-GSK1278863 oral solution | Drug | It is a clear, colorless solution. Participants will receive 125 mL of 200 µg/mL of [14C]-GSK1278863 oral solution (total dose: 25 mg). |
|
| Daprodustat 6 mg oral tablet | Drug | It is a 9.0 millimeter (mm) round, white film coated tablet. |
|
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.
| 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 |
| AUC (0-t) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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. | 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 |
| Cmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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 |
| Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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. | 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 |
| Tmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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 |
| Apparent Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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. | 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 |
| T1/2 of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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 |
| Volume of Distribution at Steady State (Vss) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863 | 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. | 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 |
| Vss of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863 | 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. | 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 |
| Total Systemic Clearance (CL) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863 | 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. | 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 |
| CL of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863 | 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. | 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 |
| Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863 | 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. | 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 2 |
| Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863 | Fecal samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in feces. | 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 2 |
| Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time | 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. | 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 2 |
| AUC(0-t) of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| Cmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| Tmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| T1/2 of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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 |
| Vss of GSK1278863 in Plasma Following IV Dose Administration | 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. | 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 |
| Vss of GSK1278863 Metabolites in Plasma Following IV Dose Administration | 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. | 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 |
| CL of GSK1278863 in Plasma Following IV Dose Administration | 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. | 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 |
| CL of GSK1278863 Metabolites in Plasma Following IV Dose Administration | 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. | 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 |
| Absolute Bioavailability of GSK1278863 Following Oral Dosing | 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. | 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 |
| Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | 0-8 hours, 10-12 hours in period 2 |
| Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | 0-24 hours in period 2 |
| Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | 0-120 hours in period 2 |
| Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion | 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. | 3 hours post-oral dose in period 1 |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study 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. | Up to 43 days |
| Number of Participants With AEs at a Particular Severity | 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. | Up to 43 days |
| Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range | 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. | Up to 43 days |
| Number of Participants With Worst Case Hematology Results Relative to Normal Range | 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. | Up to 43 days |
| Number of Participants With Abnormal Urinalysis Findings | 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. | Up to 43 days |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 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. | Pre-dose (on Day 1) and Day 8 in treatment period 2; 144 hours (Day 7) in treatment period 1 |
| Change From Baseline in Blood Pressure | 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. | 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 2 |
| Change From Baseline in Heart Rate | 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. | 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 2 |
| Change From Baseline in Respiratory Rate | 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. | 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 2 |
| Change From Baseline in Body Temperature | 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. | 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 2 |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Title |
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| Description |
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| OG000 | [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. |
| OG001 | [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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| Primary | AUC (0-Inf) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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). | Posted | 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 |
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| Primary | 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 | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram equivalent per milliliter | 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 |
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| Primary | AUC (0-t) of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram equivalent per milliliter | 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 |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram equivalent per milliliter | 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 |
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| Primary | Cmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram equivalent per milliliter | 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 |
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| Primary | Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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 | Posted | Median | Full Range | Hour | 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 |
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| Primary | Tmax of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). | Posted | Median | Full Range | Hour | 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 |
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| Primary | Apparent Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma Following Administration of GSK1278863 | 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. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | 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 |
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| Primary | T1/2 of Total Drug-related Material (Radioactivity) in Blood Following Administration of GSK1278863 | 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. | 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. | Posted | 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 |
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| Primary | Volume of Distribution at Steady State (Vss) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863 | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 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 |
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| Primary | Vss of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863 | 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. | Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). | Posted | 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 |
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| Primary | Total Systemic Clearance (CL) of Total Drug-related Material (Radioactivity) in Plasma Following IV Dose of GSK1278863 | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | 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 |
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| Primary | CL of Total Drug-related Material (Radioactivity) in Blood Following IV Dose of GSK1278863 | 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. | Pharmacokinetic Population. Data were not collected for radiolabeled IV dose of GSK1278863 because of an error (deviation). | Posted | 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 |
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| Primary | Percentage of the Total Radioactive Dose Excreted in Urine Over Time Following a Single, Oral Dose of [14C]-GSK1278863 | 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Percent dose excreted | 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 2 |
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| Primary | Percentage of the Total Radioactive Dose Excreted in Feces Over Time Following a Single, Oral Dose of [14C]-GSK1278863 | Fecal samples were collected at the indicated time points to determine the rate and extent of excretion of total radioactivity in feces. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Percent dose excreted | 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 2 |
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| Primary | Percentage of the Total Radioactive Dose Excreted in Urine and Feces Determined as Total Excretion Over Time | 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Percent dose excreted | 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 2 |
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| Secondary | AUC (0-Inf) of GSK1278863 in Plasma Following Administration IV and Both Oral Doses | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | 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 |
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| Secondary | AUC(0-t) of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | 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 |
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| Secondary | Cmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | 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 |
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| Secondary | Tmax of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hour | 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 |
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|
| Secondary | T1/2 of GSK1278863 in Plasma Following Administration of IV and Both Oral Doses | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | 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 |
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|
| Secondary | AUC (0-Inf) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | 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 |
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|
|
| Secondary | AUC(0-t) of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | 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 |
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|
| Secondary | Cmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | 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 |
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| Secondary | Tmax of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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. | Posted | Median | Full Range | Hour | 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 |
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| Secondary | T1/2 of GSK1278863 Metabolites in Plasma Following Administration of IV and Both Oral Doses | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | 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 |
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| Secondary | Vss of GSK1278863 in Plasma Following IV Dose Administration | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | 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 |
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| Secondary | Vss of GSK1278863 Metabolites in Plasma Following IV Dose Administration | 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. | 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. | Posted | 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 |
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| Secondary | CL of GSK1278863 in Plasma Following IV Dose Administration | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | 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 |
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| Secondary | CL of GSK1278863 Metabolites in Plasma Following IV Dose Administration | 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. | 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. | Posted | 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 |
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| Secondary | Absolute Bioavailability of GSK1278863 Following Oral Dosing | 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of dose normalized AUC | 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 |
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| Secondary | Percent Radioactivity Recovered for Each Metabolite in Plasma Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | Pharmacokinetic Population | Posted | Number | Percent radioactivity | 0-8 hours, 10-12 hours in period 2 |
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| Secondary | Percent Radioactivity Recovered for Each Metabolite in Urine Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | Pharmacokinetic Population | Posted | Number | Percent radioactivity | 0-24 hours in period 2 |
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| Secondary | Percent Radioactivity Recovered for Each Metabolite in Feces Following a Single Oral Dose of [14C]-GSK1278863 at 25 mg | 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. | Pharmacokinetic Population | Posted | Number | Percent radioactivity | 0-120 hours in period 2 |
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| Secondary | Percent Radioactivity Recovered for Each Metabolite in Duodenal Bile Following a Single Dose of [14C]-GSK1278863 50 µg IV Infusion | 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. | Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. | Posted | Number | Percent radioactivity | 3 hours post-oral dose in period 1 |
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| Secondary | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study 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. | Safety Population | Posted | Count of Participants | Participants | Up to 43 days |
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| Secondary | Number of Participants With AEs at a Particular Severity | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 43 days |
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| Secondary | Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 43 days |
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| Secondary | Number of Participants With Worst Case Hematology Results Relative to Normal Range | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 43 days |
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| Secondary | Number of Participants With Abnormal Urinalysis Findings | 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. | Safety Population | Posted | Count of Participants | Participants | Up to 43 days |
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| Secondary | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Count of Participants | Participants | Pre-dose (on Day 1) and Day 8 in treatment period 2; 144 hours (Day 7) in treatment period 1 |
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| Secondary | Change From Baseline in Blood Pressure | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury | 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 2 |
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| Secondary | Change From Baseline in Heart Rate | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Beats per minute | 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 2 |
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| Secondary | Change From Baseline in Respiratory Rate | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Breaths per minute | 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 2 |
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| Secondary | Change From Baseline in Body Temperature | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). | Posted | Mean | Standard Deviation | Celsius | 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 2 |
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|
| 0 |
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | [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. | 0 | 6 | 0 | 6 | 2 | 6 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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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.
| D007263 |
| Infusions, Parenteral |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
|
| 24-48 hours; n=6 |
|
|
| 48-72 hours; n=6 |
|
|
| 72-96 hours; n=6 |
|
|
| 96-120 hours; n=6 |
|
|
| 120-144 hours; n=6 |
|
|
| 144-168 hours; n=5 |
|
|
|
| 24-48 hours; n=5 |
|
|
| 48-72 hours; n=6 |
|
|
| 72-96 hours; n=6 |
|
|
| 96-120 hours; n=5 |
|
|
| 120-144 hours; n=5 |
|
|
| 144-168 hours; n=4 |
|
|
|
| 24-48 hours; n=6 |
|
|
| 48-72 hours; n=6 |
|
|
| 72-96 hours; n=6 |
|
|
| 96-120 hours; n=6 |
|
|
| 120-144 hours; n=6 |
|
|
| 144-168 hours; n=5 |
|
|
| GSK2487818; n=6,0,6 |
|
|
| GSK2506102; n=6,0,6 |
|
|
| GSK2506104; n=6,0,5 |
|
|
| GSK2531398; n=6,0,6 |
|
|
| GSK2531401; n=6,0,6 |
|
|
| GSK2506102 |
|
| GSK2506104 |
|
| GSK2531398 |
|
| GSK2531401 |
|
| GSK2506102 |
|
| GSK2506104 |
|
| GSK2531398 |
|
| GSK2531401 |
|
| GSK2506102 |
|
| GSK2506104 |
|
| GSK2531398 |
|
| GSK2531401 |
|
| GSK2487818; n=6,0, 6 |
|
|
| GSK2506102; n=6,0, 6 |
|
|
| GSK2506104; n=6,0, 5 |
|
|
| GSK2531398; n=6,0, 6 |
|
|
| GSK2531401; n=6,0, 6 |
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|
|
| Title | Measurements |
|---|---|
|
| M3 (GSK2506104), 10-12 hours |
|
| M4 (GSK2487818), 0-8 hours |
|
| M4 (GSK2487818), 10-12 hours |
|
| M6 (GSK2531398), 0-8 hours |
|
| M6 (GSK2531398), 10-12 hours |
|
| M13 (GSK2531401), 0-8 hours |
|
| M13 (GSK2531401), 10-12 hours |
|
| M5 (GSK2506102) and M14 combined, 0-8 hours |
|
| M5 (GSK2506102) and M14 combined, 10-12 hours |
|
| Title | Measurements |
|---|---|
|
| M6 (GSK2531398) |
|
| M13 (GSK2531401) |
|
| M5 (GSK2506102) and M14 combined |
|
| Title | Measurements |
|---|---|
|
| M6 (GSK2531398) |
|
| M13 (GSK2531401) |
|
| M5 (GSK2506102) and M14 combined |
|
| Title | Measurements |
|---|---|
|
| M6 (GSK2531398) |
|
| M13 (GSK2531401) |
|
| M5 |
|
| Severe |
|
| ALT; To High |
|
| Alk Phos; To Low |
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| Alk Phos; To Normal or No Change |
|
| Alk Phos; To High |
|
| AST; To Low |
|
| AST;To Normal or No Change |
|
| AST; To High |
|
| Bilirubin; To Low |
|
| Bilirubin; To Normal or No Change |
|
| Bilirubin; To High |
|
| Calcium; To Low |
|
| Calcium; To Normal or No Change |
|
| Calcium; To High |
|
| Creatinine; To Low |
|
| Creatinine; To Normal or No Change |
|
| Creatinine; To High |
|
| Direct Bilirubin; To Low |
|
| Direct Bilirubin; To Normal or No Change |
|
| Direct Bilirubin; To High |
|
| Glucose; To Low |
|
| Glucose; To Normal or No Change |
|
| Glucose; To High |
|
| Potassium; To Low |
|
| Potassium; To Normal or No Change |
|
| Potassium; To High |
|
| Protein; To Low |
|
| Protein; To Normal or No Change |
|
| Protein; To High |
|
| Sodium; To Low |
|
| Sodium; To Normal or No Change |
|
| Sodium; To High |
|
| Urea; To Low |
|
| Urea;To Normal or No Change |
|
| Urea; To High |
|
| Basophils; To High |
|
| Eosinophils; To Low |
|
| Eosinophils; To Normal or No Change |
|
| Eosinophils; To High |
|
| MCH; To Low |
|
| MCH; To Normal or No Change |
|
| MCH; To High |
|
| MCV; To Low |
|
| MCV; To Normal or No Change |
|
| MCV; To High |
|
| Erythrocytes; To Low |
|
| Erythrocytes; To Normal or No Change |
|
| Erythrocytes; To High |
|
| Hematocrit; To Low |
|
| Hematocrit; To Normal or No Change |
|
| Hematocrit; To High |
|
| Hemoglobin; To Low |
|
| Hemoglobin; To Normal or No Change |
|
| Hemoglobin; To High |
|
| Leukocytes; To Low |
|
| Leukocytes; To Normal or No Change |
|
| Leukocytes; To High |
|
| Lymphocytes; To Low |
|
| Lymphocytes; To Normal or No Change |
|
| Lymphocytes; To High |
|
| Monocytes; To Low |
|
| Monocytes; To Normal or No Change |
|
| Monocytes; To High |
|
| Neutrophils; To Low |
|
| Neutrophils; To Normal or No Change |
|
| Neutrophils; To High |
|
| Platelets; To Low |
|
| Platelets; To Normal or No Change |
|
| Platelets; To High |
|
| Reticulocytes; To Low |
|
| Reticulocytes; To Normal or No Change |
|
| Reticulocytes; To High |
|
| Reticulocytes/Erythrocytes; To Low |
|
| Reticulocytes/Erythrocytes; To Normal or No Change |
|
| Reticulocytes/Erythrocytes; To High |
|
| 144 hours (Day 7); n= 6, 0 |
|
|
| Day 8; n=0, 6 |
|
|
| SBP; Avg 144 hours (Day 7); n=6, 6 |
|
|
| SBP; Avg Day 8; n=0,6 |
|
|
| DBP; Avg 3 hours; n=6, 6 |
|
|
| DBP; Avg 144 hours (Day 7); n=6, 6 |
|
|
| DBP; Avg Day 8; n=0,6 |
|
|
| Avg 144 hours (Day 7); n=6, 6 |
|
|
| Avg Day 8; n=0,6 |
|
|
| 144 hours (Day 7); n=6, 6 |
|
|
| Day 8; n=0,6 |
|
|
| 144 hours (Day 7); n=6, 6 |
|
|
| Day 8; n=0,6 |
|
|