First-time-in-Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single (in Both Fed and Fasted States) or Repeat Doses of GSK3358699
A Randomised, Double-blind (Sponsor Open), Placebo-controlled, Three Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single (in Both Fed and Fasted States) or Repeat Doses of GSK3358699 in Healthy Male Participants
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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Cambridge, United Kingdom, CB2 2GG
- GSK Investigational Site
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
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Experimental: GSK3358699, Part A, Cohort 1
Part A will comprise of 4 TPs.
The subjects in this cohort will receive GSK3358699, as single escalation dose, during TP (1 to 3) with planned escalated doses as 1 mg, 10 mg and 35 mg.
Dose of 1 mg will be given as solution and doses of 10 mg and 35 mg, will be given as a capsule.
Each TP will be of 1 day and separated by a washout Period of 14-days.
Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10.
The subjects in cohort 1 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of GSK3358699.
The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge.
LPS dose will be based on data of study 207654 (NCT03306589).
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GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14).
This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
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Experimental: GSK3358699, Part A, Cohort 2
Part A will comprise of 4 TPs.
The subjects in this cohort will receive GSK3358699, as single escalation dose during TP (1 to 3) with planned escalated doses as 3 mg, 20 mg and 45 mg.
Dose of 3 mg will be given as solution and that of 20 and 45 mg, as capsule.
Each TP will be of 1 day and separated by a washout Period of 14-days.
Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10.
The subjects in cohort 2 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive 60 microgram per meter^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of GSK3358699.
The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion.
GM-CSF dose will be based on data of study 207654 (NCT03306589).
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GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
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Placebo Comparator: Placebo, Part A, Cohort 1
Part A will comprise of 4 TPs.
The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 1 mg and a matching placebo capsule to the study drug GSK3358699, 10 mg and 35 mg capsule, during TP (1 to 3).
Each TP will be of 1 day and separated by a washout Period of 14-days.
Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10.
The subjects in cohort 1 will receive Placebo at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of Placebo.
The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge.
LPS dose will be based on data of study 207654 (NCT03306589).
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LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14).
This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
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Placebo Comparator: Placebo, Part A, Cohort 2
Part A will comprise of 4 TPs.
The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 3 mg and a matching placebo capsule to the study drug GSK3358699, for 20 and 45 mg capsule, during TP (1 to 3).
Each TP will be of 1 day and separated by a washout Period of 14-days.
Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10.
The subjects in cohort 2 will receive Placebo at a dose level already given in TP 1-3, and will then receive 60 microgram per meter^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of Placebo.
The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion.
GM-CSF dose will be based on data of study 207654 (NCT03306589).
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This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
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Experimental: Part B, GSK3358699 under Fasted followed by Fed conditions
The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fasted condition in TP1 followed by fed condition in TP2.
This cohort intended to evaluate the effect of food.
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GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
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Experimental: Part B, GSK3358699 under Fed followed by Fasted conditions
The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fed condition in TP1 followed by fasted condition in TP2.
This cohort intended to evaluate the effect of food.
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GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
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Experimental: GSK3358699, Part C
The dose level for the first cohort in Part C will be decided following completion of Part A of the study for GSK3358699.
The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive GSK3358699, as one repeat dose treatment once daily for 14-consecutive days.
Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10.
On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter^2.
The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin).
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GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14).
This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
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Placebo Comparator: Placebo, Part C
The subjects in this cohort will receive a matching placebo to GSK3358699, Part C, as a single oral dose once daily for 14 consecutive days.
The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive placebo, as one repeat dose treatment once daily for 14-consecutive days.
Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10.
On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter^2.
The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin).
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LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14).
This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 193
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An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
Safety Population consisted of all randomized participants who took at least 1 dose of study treatment.
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Up to Day 193
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Part B: Number of Participants With AEs and SAEs
Time Frame: Up to Day 30
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
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Up to Day 30
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Part C: Number of Participants With AEs and SAEs
Time Frame: Up to Day 49
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An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
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Up to Day 49
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Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 193
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Blood samples were collected for analysis of clinical chemistry parameters.
PCI ranges were <30 grams per liter (g/L) (albumin), <2 or >2.75 millimoles/L (mmol/L) (calcium), >1.3* upper limit of normal (ULN) mmol/L (creatinine), <3 or >9 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), and <130 or >150 mmol/L (sodium).
Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category.
Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change (NC) category.
Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
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Up to Day 193
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Part A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 193
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Clinical chemistry parameters assessed were alanine aminotransferase(ALT)(<10 or >50 international units per liter[IU/L]),alkaline phosphatase(ALP)(<40 or >129 IU/L),aspartate aminotransferase(AST)(<0 or >37 IU/L),cholesterol(<2.3 or >4.9 mmol/L),direct bilirubin(DB)(<0 or >5 micromoles[mcmol]/L),high density lipoprotein (DL)(<0.9 or >1.5 mmol/L),C-reactive protein(CRP)(<0.0 or >5.0mg/liter),low DL(<0 or >3.0 mmol/L), total bilirubin (<0 or >20 mcmol/L),total protein(<63 or >83 grams/L),triglycerides(<0 or >2.3 mmol/L) and blood urea nitrogen(BUN)(<4.76 or >23.24 mg/deciliter).Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.Participants whose laboratory value category was unchanged(e.g.,High to High) or whose value became normal, are recorded in "To Normal or NC" category.Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
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Up to Day 193
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Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 30
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Blood samples were planned to be collected to analyze the chemistry parameters.
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Up to Day 30
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Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 30
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Blood samples were planned to be collected to analyze the chemistry parameters.
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Up to Day 30
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Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 28
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Blood samples were collected for analysis of chemistry parameters.
PCI ranges were <30 g/L (albumin), <2 or >2.75 mmol/L (calcium), >1.3* ULN mmol/L (creatinine), <3 or >9 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), and <130 or >150 mmol/L (sodium).
Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category.
Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category.
Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
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Up to Day 28
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Part C: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 28
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Clinical chemistry parameters assessed were ALT (<10 or >50 IU/L), ALP (<40 or >129 IU/L), AST (<0 or >37 IU/L), cholesterol (<2.3 or >4.9 mmol/L), DB (<0 or >5 mcmol/L), high DL (<0.9 or >1.5 mmol/L), CRP (<0.0 or >5.0 mg/liter), low DL (<0 or >3.0 mmol/L), total bilirubin (<0 or >20 mcmol/L), total protein (<63 or >83 grams/L), triglycerides (<0 or >2.3 mmol/L) and BUN (<4.76 or >23.24 mg/deciliter).
Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.
Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category.
Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
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Up to Day 28
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Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 193
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Blood samples collected for analysis of hematology parameters.
PCI ranges were >0.54 proportion of red blood cells in blood (hematocrit), >180 grams/liter (hemoglobin), <0.8 *10^9 cells/L (lymphocyte count), <1.5 *10^9 cells/L (total absolute neutrophil count [ANC]), <100 or >550 *10^9 cells/L (platelet count), and <3 or >20*10^9 cells/L (white blood cell [WBC] count).
Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category.
Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range 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%.
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Up to Day 193
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Part A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 193
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Hematology parameters assessed were activated partial thromboplastin time (APTT) (<25 or >37 seconds), basophil count (<0.0 or >0.1*10^9 cells/L), eosinophil count (<0.0 or >0.4*10^9 cells/L), fibrinogen (<1.5 or >4.0 g/L), mean corpuscle hemoglobin (MCH) (<26.0 or >33.5 picogram), mean corpuscle volume (MCV) (<80 or >99 femtoliter), monocyte count (<0.2 or >1.0*10^9 cells/L), prothrombin time (PT) (<10 or >12 seconds), red blood cell (RBC) count (<4.4 or >5.8*10^12 cells/L) and reticulocyte count (<0.38 or >2.64 percentage of reticulocytes).
Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.
Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category.
Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
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Up to Day 193
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Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 30
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Blood samples were planned to be collected to analyze hematology parameters.
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Up to Day 30
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Part B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 30
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Blood samples were planned to be collected to analyze hematology parameters.
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Up to Day 30
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Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 28
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Blood samples were collected for analysis of hematology parameters.
PCI ranges were >0.54 proportion of red blood cells in blood (hematocrit), >180 grams/liter (hemoglobin), <0.8*10^9 cells/L (lymphocyte count), <1.5*10^9 cells/L (total ANC), <100 or >550*10^9 cells/L (platelet count), and <3 or >20*10^9 cells/L (WBC count).
Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category.
Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range 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%.
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Up to Day 28
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Part C: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Time Frame: Up to Day 28
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Hematology parameters assessed were APTT (<25 or >37 seconds), basophil count (<0.0 or >0.1*10^9 cells/L), eosinophil count (<0.0 or >0.4*10^9 cells/L), fibrinogen (<1.5 or >4.0 g/L), MCH (<26.0 or >33.5 picogram), MCV (<80 or >99 femtoliter), monocyte count (<0.2 or >1.0*10^9 cells/L), PT (<10 or >12 seconds), RBC count (<4.4 or >5.8*10^12 cells/L) and reticulocyte count (<0.38 or >2.64 percentage of reticulocytes).
Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.
Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category.
Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
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Up to Day 28
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Part A: Number of Participants With Abnormal Urinalysis Parameters
Time Frame: Up to Day 193
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Urine samples were collected from participants for analyzing the following urine parameters: potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick.
Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells per high-power field (cells/HPF).
Number of participants with abnormal urinalysis result by microscopic examination have been presented.
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Up to Day 193
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Part B: Number of Participants With Abnormal Urinalysis Parameters
Time Frame: Up to Day 30
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Urine samples were planned to be collected to analyze urine parameters.
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Up to Day 30
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Part C: Number of Participants With Abnormal Urinalysis Parameters
Time Frame: Up to Day 28
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Urine samples were collected from participants for analyzing the following urine parameters: pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick.
Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells/HPF.
Number of participants with abnormal urinalysis result by microscopic examination have been presented.
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Up to Day 28
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Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 193
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Vital signs included systolic blood pressure(SBP), diastolic blood pressure(DBP), heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest.
PCI ranges were, SBP (millimeters of mercury [mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <11(low) or >20(high) and body temperature (degrees Celsius) <35.5 (low) or >38.0 (high).
Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category.
Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range 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%.
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Up to Day 193
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Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 30
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Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
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Up to Day 30
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Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time Frame: Up to Day 49
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Vital signs included SBP, DBP, heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest.
PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <11 (low) or >20 (high) and body temperature (degrees Celsius) <35.5 (low) or >38.0 (high).
Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category.
Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range 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%.
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Up to Day 49
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Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time Frame: Up to Day 193
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Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals.
Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
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.
Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
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Up to Day 193
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Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Time Frame: Up to Day 30
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Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF.
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Up to Day 30
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Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Time Frame: Up to Day 28
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Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTcF intervals.
Abnormal findings were categorized as clinically significant and not clinically significant.
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.
Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
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Up to Day 28
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Part A: Plasma Concentrations of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
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Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Pharmacokinetic (PK) parameters were calculated using standard non-compartmental analysis.
PK Population consisted of all participants in the Safety Population who received an active dose and for whom a PK sample was obtained and analyzed.
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Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
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Part B: Plasma Concentrations of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
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Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
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Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
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Part C: Plasma Concentrations of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
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Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
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Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
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Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: AUC(0-t) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: AUC(0-t) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: AUC(0-infinity) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: AUC(0-infinity) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
|
Part B: AUC(0-24) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
|
Part C: AUC(0-24) of GSK3358699
Time Frame: Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
|
|
Part A: Maximum Plasma Concentration (Cmax) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Cmax of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Cmax of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Time to Cmax (Tmax) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Tmax of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Tmax of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: t1/2 of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: t1/2 of GSK3358699
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699.
PK parameters were calculated using standard non-compartmental analysis.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Plasma Concentrations of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Plasma Concentrations of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Plasma Concentrations of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: AUC(0-t) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: AUC(0-t) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: AUC(0-t) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: AUC(0-infinity) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: AUC(0-infinity) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: AUC(0-infinity) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: AUC(0-24) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
|
Part B: AUC(0-24) of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
|
|
Part C: AUC(0-24) of GSK3206944
Time Frame: Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
|
|
Part A: Cmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Cmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Cmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Tmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Tmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Tmax of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: t1/2 of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part B: t1/2 of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
|
|
Part C: t1/2 of GSK3206944
Time Frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944.
PK parameters were calculated using standard non-compartmental analysis.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
|
|
Part A: Monocyte Intracellular Concentration of GSK3206944
Time Frame: Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
|
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
|
|
Part B: Monocyte Intracellular Concentration of GSK3206944
Time Frame: Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
|
Blood samples were planned to be collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes.
GSK3206944 is a metabolite of GSK3358699.
|
Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
|
|
Part C: Monocyte Intracellular Concentration of GSK3206944
Time Frame: Days 1 and 13: 1, 4 and 8 hour; Days 4, 8 and 12: Pre-dose; Day 14: 1, 4, 8, 24 and 48 hours post-dose
|
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes.
GSK3206944 is a metabolite of GSK3358699.
|
Days 1 and 13: 1, 4 and 8 hour; Days 4, 8 and 12: Pre-dose; Day 14: 1, 4, 8, 24 and 48 hours post-dose
|
|
Part A: Absolute Values of Monocyte Chemotactic Protein (MCP)-1, Interleukin (IL)6, Tumor Necrosis Factor (TNF) Alpha in Blood After Ex-vivo Lipopolysaccharide (LPS) Activation
Time Frame: Day 1: 1, 4, 8, 12, 24 and 48 hours
|
Whole blood samples of 1 milliliter (mL) were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
|
Day 1: 1, 4, 8, 12, 24 and 48 hours
|
|
Part B: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation
Time Frame: Day 1: 1, 4, 8, 12, 24 and 48 hours
|
Whole blood samples were planned to be collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL6 and TNF alpha) were planned to be analyzed.
|
Day 1: 1, 4, 8, 12, 24 and 48 hours
|
|
Part C: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation
Time Frame: Day 1: 1, 4 and 8 hours; Days 2, 4, 8 and 12: Pre-dose; Day 13: Pre-dose, 1, 4 and 8 hours; Day 14: Pre-dose, Pre-LPS challenge, 1, 4, 8, 24 and 48 hours
|
Whole blood samples of 1 mL were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
|
Day 1: 1, 4 and 8 hours; Days 2, 4, 8 and 12: Pre-dose; Day 13: Pre-dose, 1, 4 and 8 hours; Day 14: Pre-dose, Pre-LPS challenge, 1, 4, 8, 24 and 48 hours
|
Collaborators and Investigators
Sponsor
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Study Start
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Study Record Updates
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Last Verified
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More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- 207546
- 2017-003997-15 (EudraCT Number)
Plan for Individual participant data (IPD)
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IPD Plan Description
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- Study Protocol
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- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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