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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-004444-30 | EudraCT Number |
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This is an open-label, single-center, single group, non-randomized, two-period, single sequence, mass balance study which will enroll 6 healthy male participants. This study will assess the pharmacokinetics, balance/excretion, and metabolism of GSK3640254 in humans using [14C]-radiolabeled drug substance administered as an intravenous (IV) infusion and via the oral route. The study will also provide an assessment of GSK3640254 absorption, metabolism and excretion following administration of a [14C]-radiolabeled oral suspension. Each participant will be involved in the study for up to 10 weeks which will include a screening period, two treatment periods (treatment Periods 1 and 2) separated by a washout of at least 13 days between oral doses, and a follow-up visit 7-14 days after the last assessment in treatment Period 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension | Experimental | Participants will receive a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal. Participants will then be administered a 100 microgram (mcg) dose (approximately 3.7 kilobecquerel; 100 nano Curie) of [14C]-GSK3640254 as an IV infusion for 1 hour on Day 1 in treatment Period 1, On Day 1 in treatment Period 2, participants will receive a single oral dose of 85 mg (approximately 3.15 megabecquerel; 85 micro Curie) [14C]-GSK3640254 administered as an oral suspension with a moderate fat meal. A wash out period of at least 13 days will be maintained between oral doses of treatment periods. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3640254 Oral tablet | Drug | GSK3640254 will be available as white film-coated round tablets to be administered via oral route with meal in the morning with 240 milliliter (mL) of water at room temperature. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | Day 1: 2, 4, 6, 8, 10 hours |
| AUC(0-inf) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-inf) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with common (greater than or equal to [>=]5 percent [%]) non-serious AEs and SAEs is presented. |
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Inclusion Criteria:
Exclusion Criteria:
Male participants will be part of this study.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
A total of 5 participants were enrolled in the study. The washout time between dosing in consecutive study periods was at least 13 days.
This was an open-label, non-randomized, 2-period, single-sequence study to determine the pharmacokinetics, balance/excretion, and metabolism of radiolabeled [14C]-GSK3640254 following a single intravenous radiolabeled microtracer dose and a single oral radiolabeled dose. The study was conducted at a single center in the United Kingdom.
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| ID | Title | Description |
|---|---|---|
| FG000 | GSK3640254 Tablet+[14C]-GSK3640254 IV/ [14C]-GSK3640254 Oral Suspension | Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of [14C]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. In Treatment Period 2 on Day 1, participants were administered a single oral dose of 85 mg [14C]-GSK3640254 as an oral suspension with a moderate fat meal. The treatment periods were separated by a washout period of at least 13 days between oral doses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (8 Days) |
| |||||||||||||
| Treatment Period 2 (8 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GSK3640254 Tablet+[14C]-GSK3640254 IV/ [14C]-GSK3640254 Oral Suspension | Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of [14C]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. In Treatment Period 2 on Day 1, participants were administered a single oral dose of 85 mg [14C]-GSK3640254 as an oral suspension with a moderate fat meal. The treatment periods were separated by a washout period of at least 13 days between oral doses. |
| Units | Counts |
|---|---|
| Participants |
|
| 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]) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population comprised of all participants in the Safety Population (all participants who took atleast one dose of study intervention) who had at least 1 non-missing PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
|
All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.
SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment.
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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 | GSK3640254 Tablet+[14C]-GSK3640254 IV | Participants were administered a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal, followed by an intravenous (IV) infusion of [14C]-GSK3640254 100 micrograms for 1 hour on Day 1 in Treatment Period 1. The treatment periods were separated by a washout period of at least 13 days between oral doses. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | ViiV Healthcare | 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 | Jun 10, 2020 | Sep 27, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 11, 2020 | Sep 27, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C000723722 | GSK3640254 |
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Participants will receive non-radiolabeled GSK3640254 oral tablets concomitantly with radiolabeled [14C]-GSK3640254 administered as an IV infusion in treatment Period 1 and radiolabeled [14C]-GSK3640254 as an oral suspension in treatment Period 2.
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This will be an open-label study.
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| [14C]-GSK3640254 intravenous infusion | Drug | [14C]-GSK3640254 will be available as clear, colorless solution free from visible particulates to be administered via the IV route. |
|
| [14C]-GSK3640254 powder | Drug | [14C]-GSK3640254 will be available as white powder to be reconstituted into a suspension with 25 mL of vehicle before dosing so as to administer 85 mg dose with meal in the morning. |
|
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
| Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-inf) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-inf) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as AUC(0-inf) is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. | Day 1: 2, 4, 6, 8, 10 hours |
| AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | Day 1: 2, 4, 6, 8, 10 hours |
| AUC(0-t) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-t) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC (0-t) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-t) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | Day 1: 2, 4, 6, 8, 10 hours |
| Maximum Observed Concentration (Cmax) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | Day 1: 2, 4, 6, 8, 10 hours |
| Cmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Cmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Cmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Cmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | Day 1: 2, 4, 6, 8, 10 hours |
| Time of Occurrence of Cmax (Tmax) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | Day 1: 2, 4, 6, 8, 10 hours |
| Tmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Tmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Tmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Tmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | Day 1: 2, 4, 6, 8, 10 hours |
| Terminal Phase Half-life (T1/2) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | Day 1: 2, 4, 6, 8, 10 hours |
| T1/2 in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| T1/2 of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| T1/2 in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| T1/2 of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as T1/2 is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. | Day 1: 2, 4, 6, 8, 10 hours |
| Volume of Distribution at Steady State (Vss) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Clearance (CL) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Renal Clearance (CLr) Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative amount [Ae][Urine] for Period 1)/(Plasma AUC[0-inf]). | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| CLr Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative Ae[Urine] for Period 2)/(Plasma AUC[0-inf]). | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Oral Clearance (CL/F) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| CL/F in Plasma Following Administration Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Apparent Volume of Distribution (Vz/F) Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Vz/F Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Absolute Oral Bioavailability of GSK3640254 | Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(Oral Tablet)/Dose(Oral Tablet) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses were analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Percentage of Drug Escaping First Pass Hepatic Clearance (Fh) Following Administration of [14C]-GSK3640254 IV | Blood samples were collected at the indicated time points for PK analysis. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute). | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Percentage of Drug Absorbed (Fa) Following Administration of [14C]-GSK3640254 Oral Suspension | Blood samples were collected at the indicated time points for PK analysis. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Percentage of Drug Escaping Gut Metabolism (Fg) Following Administration of [14C]-GSK3640254 Oral Suspension | Blood samples were collected at the indicated time points for PK analysis. Fg is defined as the fraction metabolized by gut wall as a fraction of the oral dose and was expressed as 1 minus Metabolite load following intravenous and oral administration multiplied by 100. | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
| Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254 | Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. Not applicable (NA) indicates that No concentration values detected for pre-dose. | Day 1 (Pre-dose), 5, 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
| Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254 | Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
| Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254 | Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. NA indicates that No concentration values detected for pre-dose. | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
| Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254 | Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
| Up to 50 days |
| Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline | Blood samples were collected to analyze following hematology parameters; Basophils, Eosinophils, Erythrocytes mean corpuscular hemoglobin (MCH), Erythrocytes mean corpuscular volume (MCV), Erythrocytes, Hematocrit (HCT), Hemoglobin (Hb), Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes and Reticulocytes/Erythrocytes. Participants were counted in worst case category if their value changed to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.] High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline value=latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. | Baseline (Day 1: pre-dose) and Up to 50 Days |
| Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline | Blood samples were collected to analyze following clinical chemistry parameters:Alanine aminotransferase(ALT),albumin,alkaline phosphatase(ALP),aspartate aminotransferase(AST),bilirubin,calcium,chloride,cholesterol,creatinine,direct bilirubin,globulin,glucose,high-density lipoprotein (HDL) cholesterol,low-density lipoprotein (LDL) cholesterol,phosphate,potassium,protein,sodium,triglycerides,urate and urea.Participants were counted in worst case category if their value changed to(low,normal or high),unless there was no change in their category.Participants whose laboratory value category was unchanged(e.g. High to High),or whose value became normal,were recorded in the 'To Normal or No Change' category.Participants were counted twice if the participant had values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline value=latest pre-dose assessment(prior to oral dose) in each treatment period,with a non-missing value,including those from unscheduled visits | Baseline (Day 1: pre-dose) and Up to 50 Days |
| Number of Participants With Clinically Significant Urinalysis Findings | Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and potential of Hydrogen (pH). Number of participants with clinically significant urinalysis findings are presented. | Up to 50 days |
| Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings | 12-lead ECGs were recorded with the participants in semi-supine position after 5 minutes rest using an automated ECG machine that measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal, not clinically significant (NCS) and Clinically significant (CS) ECG findings for worst case post-Baseline are presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. | Baseline (Day 1: pre-dose) and Up to 50 days |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
| Change From Baseline in Pulse Rate | Pulse rate was measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
| Change From Baseline in Respiratory Rate | Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
| Change From Baseline in Temperature | Temperature was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 1: pre-dose), Day 1 (4 hours), 36, 72, 96, 120, 144, 168 hours and Day 8 |
| Change From Baseline in Weight | Weight was measured and recorded. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 1: pre-dose) and up to Day 8 |
| Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for analysis of total radioactivity in blood to plasma. It was calculated as Radioactivity Concentration in blood (Cb) divided by Radioactivity Concentration in plasma (Cp). | Day 1: 2, 4, 6, 8 and 10 hours |
| Years |
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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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| Primary | AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | AUC(0-inf) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-inf) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-inf) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-inf) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as AUC(0-inf) is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | AUC(0-t) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-t) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC (0-t) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-t) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Maximum Observed Concentration (Cmax) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Cmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Cmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Cmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Cmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram Equivalent per milliliter | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram Equivalent per milliliter | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Time of Occurrence of Cmax (Tmax) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | PK Population. | Posted | Median | Full Range | Hours | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Tmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Tmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Tmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Tmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. | PK Population | Posted | Median | Full Range | Hours | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Terminal Phase Half-life (T1/2) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | T1/2 in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | T1/2 of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | T1/2 in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | T1/2 of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as T1/2 is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Day 1: 2, 4, 6, 8, 10 hours |
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| Primary | Volume of Distribution at Steady State (Vss) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Clearance (CL) in Plasma Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Renal Clearance (CLr) Following Administration of IV Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative amount [Ae][Urine] for Period 1)/(Plasma AUC[0-inf]). | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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|
| Primary | CLr Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative Ae[Urine] for Period 2)/(Plasma AUC[0-inf]). | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Oral Clearance (CL/F) in Plasma Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | CL/F in Plasma Following Administration Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Apparent Volume of Distribution (Vz/F) Following Administration of Oral Dose of GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Vz/F Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Absolute Oral Bioavailability of GSK3640254 | Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(Oral Tablet)/Dose(Oral Tablet) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses were analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio of dose normalized AUC | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Percentage of Drug Escaping First Pass Hepatic Clearance (Fh) Following Administration of [14C]-GSK3640254 IV | Blood samples were collected at the indicated time points for PK analysis. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute). | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of drug escaped | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Percentage of Drug Absorbed (Fa) Following Administration of [14C]-GSK3640254 Oral Suspension | Blood samples were collected at the indicated time points for PK analysis. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of drug absorbed | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Percentage of Drug Escaping Gut Metabolism (Fg) Following Administration of [14C]-GSK3640254 Oral Suspension | Blood samples were collected at the indicated time points for PK analysis. Fg is defined as the fraction metabolized by gut wall as a fraction of the oral dose and was expressed as 1 minus Metabolite load following intravenous and oral administration multiplied by 100. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of drug escaped | Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose |
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| Primary | Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254 | Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. Not applicable (NA) indicates that No concentration values detected for pre-dose. | PK Population | Posted | Mean | Standard Deviation | Percentage of dose excreted | Day 1 (Pre-dose), 5, 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
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| Primary | Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254 | Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. | PK Population | Posted | Mean | Standard Deviation | Percentage of dose excreted | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
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| Primary | Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254 | Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. NA indicates that No concentration values detected for pre-dose. | PK Population | Posted | Mean | Standard Deviation | Percentage of dose excreted | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144 and 163 hours post-dose |
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| Primary | Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254 | Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. | PK Population | Posted | Mean | Standard Deviation | Percentage of dose excreted | Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose |
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| Secondary | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with common (greater than or equal to [>=]5 percent [%]) non-serious AEs and SAEs is presented. | Safety Population comprised of all participants who received at least one dose of study intervention. | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline | Blood samples were collected to analyze following hematology parameters; Basophils, Eosinophils, Erythrocytes mean corpuscular hemoglobin (MCH), Erythrocytes mean corpuscular volume (MCV), Erythrocytes, Hematocrit (HCT), Hemoglobin (Hb), Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets, Reticulocytes and Reticulocytes/Erythrocytes. Participants were counted in worst case category if their value changed to (low, normal or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.] High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline value=latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. | Safety Population | Posted | Count of Participants | Participants | Baseline (Day 1: pre-dose) and Up to 50 Days |
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| Secondary | Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline | Blood samples were collected to analyze following clinical chemistry parameters:Alanine aminotransferase(ALT),albumin,alkaline phosphatase(ALP),aspartate aminotransferase(AST),bilirubin,calcium,chloride,cholesterol,creatinine,direct bilirubin,globulin,glucose,high-density lipoprotein (HDL) cholesterol,low-density lipoprotein (LDL) cholesterol,phosphate,potassium,protein,sodium,triglycerides,urate and urea.Participants were counted in worst case category if their value changed to(low,normal or high),unless there was no change in their category.Participants whose laboratory value category was unchanged(e.g. High to High),or whose value became normal,were recorded in the 'To Normal or No Change' category.Participants were counted twice if the participant had values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline value=latest pre-dose assessment(prior to oral dose) in each treatment period,with a non-missing value,including those from unscheduled visits | Safety Population | Posted | Count of Participants | Participants | Baseline (Day 1: pre-dose) and Up to 50 Days |
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| Secondary | Number of Participants With Clinically Significant Urinalysis Findings | Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and potential of Hydrogen (pH). Number of participants with clinically significant urinalysis findings are presented. | Safety Population | Posted | Count of Participants | Participants | Up to 50 days |
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| Secondary | Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings | 12-lead ECGs were recorded with the participants in semi-supine position after 5 minutes rest using an automated ECG machine that measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal, not clinically significant (NCS) and Clinically significant (CS) ECG findings for worst case post-Baseline are presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. | Safety Population | Posted | Count of Participants | Participants | Baseline (Day 1: pre-dose) and Up to 50 days |
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| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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| Secondary | Change From Baseline in Pulse Rate | Pulse rate was measured in semi-supine position after 5 minutes rest with a completely automated device. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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| Secondary | Change From Baseline in Respiratory Rate | Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1: pre-dose), Day 1 (4 hours) and Day 8 |
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| Secondary | Change From Baseline in Temperature | Temperature was measured in semi-supine position after 5 minutes rest. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Degree Celsius | Baseline (Day 1: pre-dose), Day 1 (4 hours), 36, 72, 96, 120, 144, 168 hours and Day 8 |
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| Secondary | Change From Baseline in Weight | Weight was measured and recorded. Baseline value is defined as the latest pre-dose assessment (prior to the oral dose) in each treatment period, with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Safety Population | Posted | Mean | Standard Deviation | Kilograms | Baseline (Day 1: pre-dose) and up to Day 8 |
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| Secondary | Total Radioactivity in Blood to Plasma Following Administration of Oral Dose of [14C]-GSK3640254 | Blood samples were collected at the indicated time points for analysis of total radioactivity in blood to plasma. It was calculated as Radioactivity Concentration in blood (Cb) divided by Radioactivity Concentration in plasma (Cp). | PK Population | Posted | Mean | Standard Deviation | Ratio | Day 1: 2, 4, 6, 8 and 10 hours |
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|
| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | [14C]-GSK3640254 Oral Suspension | Participants were administered a single oral dose of 85 mg [14C]-GSK3640254 as an oral suspension with a moderate fat meal in Treatment Period 2 on Day 1. The treatment periods were separated by a washout period of at least 13 days between oral doses. | 0 | 5 | 0 | 5 | 1 | 5 |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
|
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.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012897 | Slow Virus Diseases |
| Title | Measurements |
|---|---|
|
| 48 hours |
|
| 72 hours |
|
| 96 hours |
|
| 120 hours |
|
| 144 hours |
|
| 163 hours |
|
| Title | Measurements |
|---|---|
|
| 72 hours |
|
| 96 hours |
|
| 120 hours |
|
| 144 hours |
|
| 168 hours |
|
| 192 hours |
|
| 216 hours |
|
| 240 hours |
|
| 264 hours |
|
| 288 hours |
|
| Title | Measurements |
|---|---|
|
| 72 hours |
|
| 96 hours |
|
| 120 hours |
|
| 144 hours |
|
| 163 hours |
|
| Title | Measurements |
|---|---|
|
| 72 hours |
|
| 96 hours |
|
| 120 hours |
|
| 144 hours |
|
| 168 hours |
|
| 192 hours |
|
| 216 hours |
|
| 240 hours |
|
| 264 hours |
|
| 288 hours |
|
| Basophils, To High |
|
| Eosinophils, To Low |
|
| Eosinophils, To Normal or No Change |
|
| Eosinophils, To High |
|
| Erythrocytes MCH, To Low |
|
| Erythrocytes MCH, To Normal or No Change |
|
| Erythrocytes MCH, To High |
|
| Erythrocytes MCV, To Low |
|
| Erythrocytes MCV, To Normal or No Change |
|
| Erythrocytes 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 |
|
| ALT, To High |
|
| Albumin, To Low |
|
| Albumin, To Normal or No Change |
|
| Albumin, To High |
|
| ALP, To Low |
|
| ALP, To Normal or No Change |
|
| ALP, 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 |
|
| Chloride, To Low |
|
| Chloride, To Normal or No Change |
|
| Chloride, To High |
|
| Cholesterol, To Low |
|
| Cholesterol, To Normal or No Change |
|
| Cholesterol, 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 |
|
| Globulin, To Low |
|
| Globulin, To Normal or No Change |
|
| Globulin, To High |
|
| Glucose, To Low |
|
| Glucose, To Normal or No Change |
|
| Glucose, To High |
|
| HDL Cholesterol, To Low |
|
| HDL Cholesterol, To Normal or No Change |
|
| HDL Cholesterol, To High |
|
| LDL Cholesterol, To Low |
|
| LDL Cholesterol, To Normal or No Change |
|
| LDL Cholesterol, To High |
|
| Phosphate, To Low |
|
| Phosphate, To Normal or No Change |
|
| Phosphate, 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 |
|
| Triglycerides, To Low |
|
| Triglycerides, To Normal or No Change |
|
| Triglycerides, To High |
|
| Urate, To Low |
|
| Urate, To Normal or No Change |
|
| Urate, To High |
|
| Urea, To Low |
|
| Urea, To Normal or No Change |
|
| Urea, To High |
|
| DBP: Day 1 (4 hours); n = 5, 4 |
|
|
| SBP: Day 8; n= 5, 5 |
|
|
| DBP: Day 8; n= 5, 5 |
|
|
| Pulse rate: Day 8; n= 5, 5 |
|
|
| Respiratory rate: Day 8; n= 5, 5 |
|
|
| Temperature: 36 hours; n= 5, 5 |
|
|
| Temperature: 72 hours; n= 5, 5 |
|
|
| Temperature: 96 hours; n= 5, 5 |
|
|
| Temperature: 120 hours; n= 5, 5 |
|
|
| Temperature: 144 hours; n= 5, 5 |
|
|
| Temperature: 168 hours; n= 5, 5 |
|
|
| Temperature: Day 8; n= 5, 5 |
|
|
| Title | Measurements |
|---|---|
|
| 8 hours |
|
| 10 hours |
|