| Primary | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. | | OG001 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG003 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG004 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | | OG005 | Part A: GSK3358699 25 mg SD | Participants in Part A received a SD of GSK3358699 25 mg on Day 1 in treatment Period 4. On Day 1, participants were administered a SD of GSK3358699 25 mg followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 were administered via the oral route. | | OG006 | Part A: GSK3358699 30 mg SD | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | | OG007 | Part A: GSK3358699 40 mg SD | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
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| AEs | | |
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| Primary | Part B: Number of Participants With AEs and SAEs | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With AEs and SAEs | 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. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 49 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). |
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| Primary | Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | 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%. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. | |
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| Primary | Part A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | 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%. | Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. |
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| Primary | Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline | Blood samples were planned to be collected to analyze the chemistry parameters. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Blood samples were planned to be collected to analyze the chemistry parameters. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline | 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%. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | |
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| Primary | Part C: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | 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%. | Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). |
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| Primary | Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline | 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%. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. |
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| Primary | Part A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline | 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%. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. |
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| Primary | Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline | Blood samples were planned to be collected to analyze hematology parameters. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline | Blood samples were planned to be collected to analyze hematology parameters. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline | 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%. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD |
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| Primary | Part C: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline | 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%. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD |
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| Primary | Part A: Number of Participants With Abnormal Urinalysis Parameters | 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. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. | | OG001 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. |
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| Primary | Part B: Number of Participants With Abnormal Urinalysis Parameters | Urine samples were planned to be collected to analyze urine parameters. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With Abnormal Urinalysis Parameters | 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. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). |
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| Primary | Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | 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%. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. |
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| Primary | Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | 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%. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 49 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 |
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| Primary | Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | 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. | | Posted | | Count of Participants | | Participants | | Up to Day 193 | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. | | OG001 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. |
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| Primary | Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings | Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Up to Day 30 | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Primary | Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings | 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. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Count of Participants | | Participants | | Up to Day 28 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). |
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| Secondary | Part A: Plasma Concentrations of GSK3358699 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). | Posted | | Median | Full Range | Nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 |
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| Secondary | Part B: Plasma Concentrations of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: Plasma Concentrations of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
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| Secondary | Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
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| Secondary | Part B: AUC(0-t) of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: AUC(0-t) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
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| Secondary | Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | |
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| Secondary | Part B: AUC(0-infinity) of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: AUC(0-infinity) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
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| Secondary | Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | |
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| Secondary | Part B: AUC(0-24) of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: AUC(0-24) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. |
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| Secondary | Part A: Maximum Plasma Concentration (Cmax) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | | Posted | | Median | Full Range | Nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
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| Secondary | Part B: Cmax of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: Cmax of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | |
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| Secondary | Part A: Time to Cmax (Tmax) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | | Posted | | Median | Full Range | Hours | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
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| Secondary | Part B: Tmax of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: Tmax of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | |
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| Secondary | Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
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| Secondary | Part B: t1/2 of GSK3358699 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: t1/2 of GSK3358699 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | |
|
| Secondary | Part A: Plasma Concentrations of GSK3206944 | 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. | | Posted | | Median | Full Range | Nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: Plasma Concentrations of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: Plasma Concentrations of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 |
|
| Secondary | Part A: AUC(0-t) of GSK3206944 | 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. | | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: AUC(0-t) of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: AUC(0-t) of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
|
| Secondary | Part A: AUC(0-infinity) of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | |
|
| Secondary | Part B: AUC(0-infinity) of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: AUC(0-infinity) of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
|
| Secondary | Part A: AUC(0-24) of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | |
|
| Secondary | Part B: AUC(0-24) of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: AUC(0-24) of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours*nanogram per milliliter | | Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | |
|
| Secondary | Part A: Cmax of GSK3206944 | 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. | | Posted | | Median | Full Range | Nanogram per milliliter | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: Cmax of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: Cmax of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
|
| Secondary | Part A: Tmax of GSK3206944 | 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. | | Posted | | Median | Full Range | Hours | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: Tmax of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: Tmax of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
|
| Secondary | Part A: t1/2 of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed. | Posted | | Median | Full Range | Hours | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: t1/2 of GSK3206944 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: t1/2 of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Hours | | 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 | | | | ID | Title | Description |
|---|
| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD |
|
| Secondary | Part A: Monocyte Intracellular Concentration of GSK3206944 | 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. | | Posted | | Median | Full Range | Nanogram per milliliter | | Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | | OG001 | Part A: GSK3358699 3 mg SD | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | | OG002 | Part A: GSK3358699 10 mg SD | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | | OG003 | Part A: GSK3358699 20 mg SD | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. |
|
| Secondary | Part B: Monocyte Intracellular Concentration of GSK3206944 | 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. | PK Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period | | | | ID | Title | Description |
|---|
| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
| |
| Secondary | Part C: Monocyte Intracellular Concentration of GSK3206944 | 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. | PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for Cohorts 6 to 8 as no participants were enrolled. | Posted | | Median | Full Range | Nanogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM-CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 6- GSK3358699 RD | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | | OG002 | Part C: Cohort 7- GSK3358699 RD | |
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| Secondary | 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 | 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. | Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data was not collected for GSK3358699 25 mg SD arm. | Posted | | Median | Full Range | Picogram per milliliter | | Day 1: 1, 4, 8, 12, 24 and 48 hours | | | | ID | Title | Description |
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| OG000 | Part A: Placebo SD | Participants in Part A received a SD of placebo on Day 1 in either treatment Period 1, 2 and 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg for induction of blisters on the forearm in Cohort 1 and in Cohort 2, participants were administered with IV administration of in vivo GM-CSF challenge at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. Placebo were administered via the oral route. | | OG001 | Part A: GSK3358699 1 mg SD | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. |
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| Secondary | Part B: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B. | Posted | | | | | | Day 1: 1, 4, 8, 12, 24 and 48 hours | | | | ID | Title | Description |
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| OG000 | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. | | OG001 | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Participants in Part B Cohort 3 were planned to receive a SD of GSK3358699 under fasted conditions on Day 1 in treatment Period 1; followed by a SD of GSK3358699 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 14 days between each treatment period. |
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| Secondary | Part C: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation | 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. | Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). | Posted | | Median | Full Range | Picogram per milliliter | | 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 | | | | ID | Title | Description |
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| OG000 | Part C: Cohort 4 and 5- Placebo RD | Participants received once daily RD of placebo on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM CSF was followed by blister induction on forearm (0.2% cantharidin). | | OG001 | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Participants received once daily repeat dose of GSK3358699 10 mg on Days 1 to 14. In Cohort 4, on Day 14, participants were administered an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo at a dose of 60 mcg/m^2. The administration of LPS or GM CSF was followed by blister induction on forearm (0.2% cantharidin). |
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