First-time-in-Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single (in Both Fed and Fasted States) or Repeat Doses of GSK3358699
Study Details
Study Description
Brief Summary
This FTIH study, intends to identify the doses of GSK3358699, which are well tolerated by the subjects whilst delivering a robust pharmacodynamic (PD) response. This study will evaluate the safety, tolerability, pharmacokinetic (PK) and PD profile of single (in both fed and fasted states) and multiple ascending doses of GSK3358699 in healthy male subjects within a pre-defined and controlled pharmacodynamic and pharmacokinetic range for each cohort. It also intends to understand the effect of GSK3358699 on systemic markers of inflammation following low dose in vivo lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) challenge and local inflammation in cantharidin-induced blisters. The study has been carefully designed to explore the in vivo biology of the target and the potential for the study drug to become a transformative medicine for subjects in multiple immuno-inflammatory disease indications.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
Subjects who are enrolled in the dose escalation treatment Periods of Part A may choose to only take part in the dose escalation treatment Periods 1-3, or may choose to also take part in the challenge Treatment Period (Period 4). If a subject chooses to participate in the dose escalation treatment Periods 1-3 only, or does not (at screening) meet the eligibility criteria specific to challenges (treatment Period 4), a new subject will be recruited for treatment Period 4 only and will be regarded as a replacement subject. The study will be conducted in three Parts. Total duration for participation will be approximately 19 weeks for subjects taking part in all three dose escalation treatment Periods and 23 weeks if a subject takes part in all four treatment Periods of Part A. For replacement subjects only taking part in the challenge treatment Period (Period 4), approximate study duration will be 10 weeks. Total duration for participation will be approximately 9 weeks for Part B and 12 weeks for Part C. The study will be conducted in up to 80 subjects.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: GSK3358699, Part A, Cohort 1 Part A will comprise of 4 TPs. The subjects in this cohort will receive GSK3358699, as single escalation dose, during TP (1 to 3) with planned escalated doses as 1 mg, 10 mg and 35 mg. Dose of 1 mg will be given as solution and doses of 10 mg and 35 mg, will be given as a capsule. Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 1 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of GSK3358699. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge. LPS dose will be based on data of study 207654 (NCT03306589). |
Drug: GSK3358699
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
Biological: LPS
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14). This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
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Experimental: GSK3358699, Part A, Cohort 2 Part A will comprise of 4 TPs. The subjects in this cohort will receive GSK3358699, as single escalation dose during TP (1 to 3) with planned escalated doses as 3 mg, 20 mg and 45 mg. Dose of 3 mg will be given as solution and that of 20 and 45 mg, as capsule. Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 2 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive 60 microgram per meter^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of GSK3358699. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion. GM-CSF dose will be based on data of study 207654 (NCT03306589). |
Drug: GSK3358699
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
Biological: GM-CSF
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
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Placebo Comparator: Placebo, Part A, Cohort 1 Part A will comprise of 4 TPs. The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 1 mg and a matching placebo capsule to the study drug GSK3358699, 10 mg and 35 mg capsule, during TP (1 to 3). Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 1 will receive Placebo at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of Placebo. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge. LPS dose will be based on data of study 207654 (NCT03306589). |
Drug: Placebo
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
Biological: LPS
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14). This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
|
Placebo Comparator: Placebo, Part A, Cohort 2 Part A will comprise of 4 TPs. The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 3 mg and a matching placebo capsule to the study drug GSK3358699, for 20 and 45 mg capsule, during TP (1 to 3). Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 2 will receive Placebo at a dose level already given in TP 1-3, and will then receive 60 microgram per meter^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of Placebo. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion. GM-CSF dose will be based on data of study 207654 (NCT03306589). |
Drug: Placebo
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
Biological: GM-CSF
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
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Experimental: Part B, GSK3358699 under Fasted followed by Fed conditions The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fasted condition in TP1 followed by fed condition in TP2. This cohort intended to evaluate the effect of food. |
Drug: GSK3358699
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
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Experimental: Part B, GSK3358699 under Fed followed by Fasted conditions The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fed condition in TP1 followed by fasted condition in TP2. This cohort intended to evaluate the effect of food. |
Drug: GSK3358699
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
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Experimental: GSK3358699, Part C The dose level for the first cohort in Part C will be decided following completion of Part A of the study for GSK3358699. The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive GSK3358699, as one repeat dose treatment once daily for 14-consecutive days. Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10. On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter^2. The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin). |
Drug: GSK3358699
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
Biological: GM-CSF
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Biological: LPS
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14). This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
|
Placebo Comparator: Placebo, Part C The subjects in this cohort will receive a matching placebo to GSK3358699, Part C, as a single oral dose once daily for 14 consecutive days. The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive placebo, as one repeat dose treatment once daily for 14-consecutive days. Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10. On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter^2. The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin). |
Drug: Placebo
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
Biological: GM-CSF
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
Biological: LPS
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14). This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
Other: Cantharidin
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
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Outcome Measures
Primary Outcome Measures
- Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Day 193]
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.
- Part B: Number of Participants With AEs and SAEs [Up to Day 30]
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.
- Part C: Number of Participants With AEs and SAEs [Up to Day 49]
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.
- Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline [Up to Day 193]
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%.
- Part A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 193]
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%.
- Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 30]
Blood samples were planned to be collected to analyze the chemistry parameters.
- Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 30]
Blood samples were planned to be collected to analyze the chemistry parameters.
- Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 28]
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%.
- Part C: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 28]
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%.
- Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 193]
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%.
- Part A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 193]
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%.
- Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 30]
Blood samples were planned to be collected to analyze hematology parameters.
- Part B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 30]
Blood samples were planned to be collected to analyze hematology parameters.
- Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 28]
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%.
- Part C: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to Day 28]
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%.
- Part A: Number of Participants With Abnormal Urinalysis Parameters [Up to Day 193]
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.
- Part B: Number of Participants With Abnormal Urinalysis Parameters [Up to Day 30]
Urine samples were planned to be collected to analyze urine parameters.
- Part C: Number of Participants With Abnormal Urinalysis Parameters [Up to Day 28]
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.
- Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 193]
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%.
- Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 30]
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
- Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline [Up to Day 49]
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%.
- Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings [Up to Day 193]
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.
- Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings [Up to Day 30]
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF.
- Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings [Up to Day 28]
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.
Secondary Outcome Measures
- Part A: Plasma Concentrations of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
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.
- Part B: Plasma Concentrations of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: Plasma Concentrations of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: AUC(0-t) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: AUC(0-t) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: AUC(0-infinity) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: AUC(0-infinity) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: AUC(0-24) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: AUC(0-24) of GSK3358699 [Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Maximum Plasma Concentration (Cmax) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: Cmax of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: Cmax of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Time to Cmax (Tmax) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: Tmax of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: Tmax of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part B: t1/2 of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
- Part C: t1/2 of GSK3358699 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
- Part A: Plasma Concentrations of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: Plasma Concentrations of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: Plasma Concentrations of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: AUC(0-t) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: AUC(0-t) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: AUC(0-t) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: AUC(0-infinity) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: AUC(0-infinity) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: AUC(0-infinity) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: AUC(0-24) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: AUC(0-24) of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: AUC(0-24) of GSK3206944 [Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: Cmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: Cmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: Cmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: Tmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: Tmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: Tmax of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: t1/2 of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part B: t1/2 of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
- Part C: t1/2 of GSK3206944 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
- Part A: Monocyte Intracellular Concentration of GSK3206944 [Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period]
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
- Part B: Monocyte Intracellular Concentration of GSK3206944 [Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period]
Blood samples were planned to be collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
- Part C: Monocyte Intracellular Concentration of GSK3206944 [Days 1 and 13: 1, 4 and 8 hour; Days 4, 8 and 12: Pre-dose; Day 14: 1, 4, 8, 24 and 48 hours post-dose]
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
- 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 [Day 1: 1, 4, 8, 12, 24 and 48 hours]
Whole blood samples of 1 milliliter (mL) were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
- Part B: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation [Day 1: 1, 4, 8, 12, 24 and 48 hours]
Whole blood samples were planned to be collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL6 and TNF alpha) were planned to be analyzed.
- Part C: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation [Day 1: 1, 4 and 8 hours; Days 2, 4, 8 and 12: Pre-dose; Day 13: Pre-dose, 1, 4 and 8 hours; Day 14: Pre-dose, Pre-LPS challenge, 1, 4, 8, 24 and 48 hours]
Whole blood samples of 1 mL were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
Eligibility Criteria
Criteria
Inclusion Criteria: - Subjects enrolled into the study, where they will be administered LPS or GM-CSF challenge, must be 18 to 55 years of age inclusive, at the time of signing the informed consent. Subjects enrolled into the study where they will not be administered LPS or GM-CSF challenge must be 18 to 65 years of age inclusive, at the time of signing the informed consent. - Subjects must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - Body weight must be > = 50 kilogram (kg) and body mass index (BMI) within the range 18.5-35.0 kg per square meter (kg/m^2) (inclusive). - Male subjects agreeing to use contraceptive methods during the treatment Period and for at least 91 days, after the last dose of study treatment and refrain from donating sperm during this Period. - Capable of giving informed consent. Exclusion Criteria: - Current or chronic history of pancreatitis, diabetes mellitus or impaired glucose tolerance, gastrointestinal disease, liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), anaphylaxis, and /or anaphylactoid (resembling anaphylaxis) reactions [Sampson et al 2006], cardiac disease including clinically significant ventricular arrhythmias or long QT syndrome, renal disease where clinically significant (minor abnormalities may be permitted base on discussion between investigator and medical monitor), respiratory disease or conditions including but not limited to asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis and any current respiratory infection (childhood asthma is not an exclusion criterion), sensitivity or severe allergic responses to any of the challenge agents or cantharidin, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation; frequent vasovagal syncope, surgery requiring general anaesthetic or significant trauma in 3 months leading to study enrolment, relevant skin conditions (e.g. recent history of eczema or recurrent eczema, keloid, skin allergies, psoriasis, atopic dermatitis, and vitiligo) which in the opinion of the investigator could pose safety issues or cause interference with study procedures, sepsis, coagulation disorders, peripheral edema, lymphangitis, lymphedema, pleural or pericardial effusion, hemorrhage (eg sub-arachnoid) or hemophilia or a related bleeding disorder. - History of malignancies e.g. recurrent basal cell carcinoma, hematological malignancy. - For subjects receiving cantharidin: Presence on either forearm of tattoos, naevi, hypertrophic scars, keloids, hyper- or hypo- pigmentation that may, in the opinion of the Investigator, interfere with study assessments. Subjects with very fair skin, very dark skin, excessive hair or any skin abnormalities that may, in the opinion of the Investigator, interfere with study assessments. - Family history of premature cardiovascular disease or long QT syndrome. - QT interval with Fridericia's correction (QTcF) > 450 millisecond (msec), based on averaged QTcF values of triplicate ECGs obtained over a brief recording period. - Unable or unwilling to refrain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study treatment until completion of the follow-up visit. Paracetamol, at a dose of <= 2 grams per day was permitted for use anytime during the study. Other concomitant medications will be considered on case by case basis. - The subjects have participated in a clinical trial and received an investigational product within the following time period prior to the first dosing day in the study: 30 days; 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or currently in a study of an investigational device. - Exposure to more than four new chemical entities within 12 months prior to the first dosing day. - Previous exposure to intravenous lipopolysaccharide (LPS) in a clinical research setting. - Alanine transaminase (ALT) >1.5x upper limit of normal (ULN) at screening. - Bilirubin
1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening. - Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. - A positive pre-study drug/alcohol screen at screening. - A positive test for human immunodeficiency virus (HIV) antibody at screening. - Persistent clinically significant abnormal C-reactive protein (CRP) levels at screening - Persistent clinically significant abnormal white cell count (WCC) levels at screening (if clinically significant abnormality is detected, WCC can be retested as clinically indicated) - Platelets < 150 x 10^9 per liter (L) at screening. - Fasted Triglycerides >3.4 millimole per liter (mmol/L) at screening. - Fasted Total cholesterol >7.7 mmol/L at screening. - Random glucose > = 11.1 mmol/L at screening. - Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL). - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. - Unable to comply with precautions to minimize phototoxicity risk.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | GSK Investigational Site | Cambridge | United Kingdom | CB2 2GG |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.- 207546
- 2017-003997-15
Study Results
Participant Flow
Recruitment Details | This was a randomized, double-blind, placebo-controlled, 3-part study. Part A was single ascending dose crossover with 2 interlocking cohorts(1 and 2);Part B was planned to be a single dose, open-label, 2-way crossover in fed, fasted conditions(Cohort3);Part C was repeat dose design in sequential cohorts(4,5) and cohorts 6 to 8 were planned. |
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Pre-assignment Detail | A total 48 participants were enrolled in this study. Part B and Part C (Cohorts 6 to 8) were not initiated as the study was terminated early due to strategic reasons following emergence of new data. Hence, no participants were enrolled in Part B and Part C (Cohorts 6 to 8). |
Arm/Group Title | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
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Arm/Group Description | Participants in Part A Cohort 1 were planned to receive a single dose (SD) of placebo (Treatment P) on Day 1 in treatment Period 1. Participants were received a SD of GSK3358699 10 milligram (mg) (Treatment C) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by intravenous (IV) administration of in vivo lipopolysaccharide (LPS) challenge at a dose of 0.75 nanograms per kilogram (ng/kg) and further treated with 0.2 percent (%) cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) at a dose of 60 micrograms per meter square (mcg/m^2) and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 were planned to receive a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1.Participants were received a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | 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. | 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. | Participants received once daily repeat dose (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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 2 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 1 | 2 | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Part A: Cohort 1-Period 1 (Day1) | |||||||||||||||||||
STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 14 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 12 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | Total |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A Cohort 1 were planned to receive a single dose (SD) of placebo (Treatment P) on Day 1 in treatment Period 1. Participants were received a SD of GSK3358699 10 milligram (mg) (Treatment C) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by intravenous (IV) administration of in vivo lipopolysaccharide (LPS) challenge at a dose of 0.75 nanograms per kilogram (ng/kg) and further treated with 0.2 percent (%) cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 40 mg (Treatment E) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 1 received a SD of GSK3358699 1 mg (Treatment A) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 10 mg (Treatment C) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo LPS challenge at a dose of 0.75 ng/kg and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) at a dose of 60 micrograms per meter square (mcg/m^2) and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of placebo (Treatment P) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 were planned to receive a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1.Participants were received a SD of placebo (Treatment P) on Day 1 in treatment Period 2; followed by a SD of GSK3358699 30 mg (Treatment F) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of placebo (Treatment P) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | Participants in Part A Cohort 2 received a SD of GSK3358699 3 mg (Treatment B) on Day 1 in treatment Period 1; followed by a SD of GSK3358699 20 mg (Treatment D) on Day 1 in treatment Period 2; followed by a SD of placebo (Treatment P) on Day 1 in treatment Period 3. On Day 1 of treatment Period 4, participants were administered a SD of GSK3358699 25 mg (Treatment R) followed by IV administration of in vivo administration of GM-CSF at a dose of 60 mcg/m^2 and further treated with 0.2% cantharidin for induction of blisters on the forearm. GSK3358699 and placebo were administered via the oral route. There was a washout period of 14 days between each treatment period. | 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. | 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. | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). | Total of all reporting groups |
Overall Participants | 1 | 2 | 2 | 2 | 2 | 4 | 1 | 3 | 1 | 2 | 1 | 2 | 0 | 0 | 11 | 14 | 0 | 0 | 0 | 48 |
Age, Customized (Count of Participants) | ||||||||||||||||||||
<=18 years |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
1
9.1%
|
|||||
>18 and <65 years |
1
100%
|
1
50%
|
2
100%
|
2
100%
|
2
100%
|
4
100%
|
1
100%
|
3
100%
|
1
100%
|
2
100%
|
1
100%
|
2
100%
|
11
Infinity
|
14
Infinity
|
47
427.3%
|
|||||
>=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
0%
|
|||||
Sex: Female, Male (Count of Participants) | ||||||||||||||||||||
Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
0%
|
|||||
Male |
1
100%
|
2
100%
|
2
100%
|
2
100%
|
2
100%
|
4
100%
|
1
100%
|
3
100%
|
1
100%
|
2
100%
|
1
100%
|
2
100%
|
11
Infinity
|
14
Infinity
|
48
436.4%
|
|||||
Race/Ethnicity, Customized (Count of Participants) | ||||||||||||||||||||
Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
Infinity
|
0
NaN
|
2
18.2%
|
|||||
White-White/Caucasian/European Heritage |
1
100%
|
2
100%
|
2
100%
|
2
100%
|
2
100%
|
3
75%
|
1
100%
|
3
100%
|
1
100%
|
2
100%
|
1
100%
|
1
50%
|
10
Infinity
|
14
Infinity
|
45
409.1%
|
|||||
Multiple |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
NaN
|
0
NaN
|
1
9.1%
|
Outcome Measures
Title | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
---|---|
Description | 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. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
AEs |
8
800%
|
2
100%
|
3
150%
|
2
100%
|
3
150%
|
8
200%
|
4
400%
|
3
100%
|
SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With AEs and SAEs |
---|---|
Description | 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. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With AEs and SAEs |
---|---|
Description | 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. |
Time Frame | Up to Day 49 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
AEs |
7
700%
|
8
400%
|
|||
SAEs |
0
0%
|
1
50%
|
Title | Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Albumin: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Albumin: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Albumin: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Calcium: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Calcium: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Calcium: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Creatinine: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Creatinine: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Creatinine: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Glucose: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Glucose: To within Range or No Change |
22
2200%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Glucose: To High |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Potassium: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Potassium: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Potassium: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sodium: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sodium: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Sodium: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
ALT: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
ALT: To Normal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
ALT: To High,n=23,5,3,6,6,12,6,6 |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
ALP: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
ALP: To Normal or NC,n=23,5,3,6,6,12,6,6 |
23
2300%
|
4
200%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
ALP: To High,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
AST: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
AST: To Normal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
AST: To High,n=23,5,3,6,6,12,6,6 |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Cholesterol: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Cholesterol: To Normal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
4
200%
|
3
150%
|
5
250%
|
5
250%
|
10
250%
|
5
500%
|
4
133.3%
|
Cholesterol: To High,n=23,5,3,6,6,12,6,6 |
1
100%
|
1
50%
|
0
0%
|
1
50%
|
1
50%
|
2
50%
|
1
100%
|
2
66.7%
|
DB: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
DB:To Normal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
5
250%
|
2
100%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
DB: To High,n=23,5,3,6,6,12,6,6 |
1
100%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
High DL: To Low,n=23,5,3,6,6,12,6,6 |
1
100%
|
2
100%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
High DL:To Normal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
2
100%
|
3
150%
|
5
250%
|
6
300%
|
11
275%
|
6
600%
|
6
200%
|
High DL: To High,n=23,5,3,6,6,12,6,6 |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
CRP: To Low,n=23,5,3,6,4,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
CRP: To Normal or NC,n=23,5,3,6,4,12,6,6 |
18
1800%
|
5
250%
|
2
100%
|
6
300%
|
4
200%
|
4
100%
|
6
600%
|
5
166.7%
|
CRP: To High,n=23,5,3,6,4,12,6,6 |
5
500%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
8
200%
|
0
0%
|
1
33.3%
|
Low DL: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Low DL: To Normal or NC,n=23,5,3,6,6,12,6,6 |
21
2100%
|
5
250%
|
2
100%
|
4
200%
|
5
250%
|
11
275%
|
5
500%
|
4
133.3%
|
Low DL: To High,n=23,5,3,6,6,12,6,6 |
2
200%
|
0
0%
|
1
50%
|
2
100%
|
1
50%
|
1
25%
|
1
100%
|
2
66.7%
|
Total bilirubin: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Total bilirubin:ToNormal or NC,n=23,5,3,6,6,12,6,6 |
22
2200%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
11
275%
|
6
600%
|
6
200%
|
Total bilirubin: To High,n=23,5,3,6,6,12,6,6 |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
Total protein: To Low,n=23,5,3,6,6,12,6,6 |
4
400%
|
0
0%
|
1
50%
|
0
0%
|
2
100%
|
3
75%
|
1
100%
|
1
33.3%
|
Total protein:To Normal or NC,n=23,5,3,6,6,12,6,6 |
19
1900%
|
5
250%
|
2
100%
|
6
300%
|
4
200%
|
9
225%
|
5
500%
|
5
166.7%
|
Total protein: To High,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Triglycerides: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Triglycerides:To Normal or NC,n=23,5,3,6,6,12,6,6 |
17
1700%
|
3
150%
|
2
100%
|
4
200%
|
4
200%
|
12
300%
|
3
300%
|
4
133.3%
|
Triglycerides: To High,n=23,5,3,6,6,12,6,6 |
6
600%
|
2
100%
|
1
50%
|
2
100%
|
2
100%
|
0
0%
|
3
300%
|
2
66.7%
|
BUN: To Low,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
BUN: To Normal or NC,n=23,5,3,6,6,12,6,6 |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
BUN: To High,n=23,5,3,6,6,12,6,6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were planned to be collected to analyze the chemistry parameters. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were planned to be collected to analyze the chemistry parameters. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
Albumin: To Low |
0
0%
|
0
0%
|
|||
Albumin: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Albumin: To High |
0
0%
|
0
0%
|
|||
Calcium: To Low |
0
0%
|
0
0%
|
|||
Calcium: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Calcium: To High |
0
0%
|
0
0%
|
|||
Creatinine: To Low |
0
0%
|
0
0%
|
|||
Creatinine: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Creatinine: To High |
0
0%
|
0
0%
|
|||
Glucose: To Low |
0
0%
|
0
0%
|
|||
Glucose: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Glucose: To High |
0
0%
|
0
0%
|
|||
Potassium: To Low |
0
0%
|
0
0%
|
|||
Potassium: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Potassium: To High |
0
0%
|
0
0%
|
|||
Sodium: To Low |
0
0%
|
0
0%
|
|||
Sodium: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Sodium: To High |
0
0%
|
0
0%
|
Title | Part C: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
ALT: To Low,n=11,14,0,0,0 |
0
0%
|
1
50%
|
|||
ALT: To Normal or NC,n=11,14,0,0,0 |
11
1100%
|
12
600%
|
|||
ALT: To High,n=11,14,0,0,0 |
0
0%
|
1
50%
|
|||
ALP: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
ALP: To Normal or NC,n=11,14,0,0,0 |
11
1100%
|
14
700%
|
|||
ALP: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
AST: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
AST: To Normal or NC,n=11,14,0,0,0 |
10
1000%
|
14
700%
|
|||
AST: To High,n=11,14,0,0,0 |
1
100%
|
0
0%
|
|||
Cholesterol: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Cholesterol: To Normal or NC,n=11,14,0,0,0 |
9
900%
|
13
650%
|
|||
Cholesterol: To High,n=11,14,0,0,0 |
2
200%
|
1
50%
|
|||
DB: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
DB:To Normal or NC,n=11,14,0,0,0 |
11
1100%
|
14
700%
|
|||
DB: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
High DL: To Low,n=11,14,0,0,0 |
1
100%
|
1
50%
|
|||
High DL:To Normal or NC,n=11,14,0,0,0 |
10
1000%
|
13
650%
|
|||
High DL: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
CRP: To Low,n=10,13,0,0,0 |
0
0%
|
0
0%
|
|||
CRP: To Normal or NC,n=10,13,0,0,0 |
9
900%
|
12
600%
|
|||
CRP: To High,n=10,13,0,0,0 |
1
100%
|
1
50%
|
|||
Low DL: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Low DL: To Normal or NC,n=11,14,0,0,0 |
8
800%
|
13
650%
|
|||
Low DL: To High,n=11,14,0,0,0 |
3
300%
|
1
50%
|
|||
Total bilirubin: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Total bilirubin:ToNormal or NC,n=11,14,0,0,0 |
11
1100%
|
14
700%
|
|||
Total bilirubin: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Total protein: To Low,n=11,14,0,0,0 |
1
100%
|
2
100%
|
|||
Total protein:To Normal or NC,n=11,14,0,0,0 |
10
1000%
|
12
600%
|
|||
Total protein: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Triglycerides: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
Triglycerides:To Normal or NC,n=11,14,0,0,0 |
10
1000%
|
13
650%
|
|||
Triglycerides: To High,n=11,14,0,0,0 |
1
100%
|
1
50%
|
|||
BUN: To Low,n=11,14,0,0,0 |
0
0%
|
0
0%
|
|||
BUN: To Normal or NC,n=11,14,0,0,0 |
11
1100%
|
14
700%
|
|||
BUN: To High,n=11,14,0,0,0 |
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Hematocrit: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hematocrit: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Hematocrit: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hemoglobin: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hemoglobin: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Hemoglobin: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Lymphocyte count: To Low |
2
200%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
50%
|
0
0%
|
0
0%
|
Lymphocyte count: To within Range or No Change |
21
2100%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
10
250%
|
6
600%
|
6
200%
|
Lymphocyte count: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Platelet count: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Platelet count: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Platelet count: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Total ANC: To Low |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Total ANC: To within Range or No Change |
23
2300%
|
4
200%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Total ANC: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
WBC: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
WBC: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
WBC: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
APTT: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
1
25%
|
0
0%
|
0
0%
|
APTT: To Normal or NC |
21
2100%
|
5
250%
|
2
100%
|
6
300%
|
4
200%
|
11
275%
|
6
600%
|
4
133.3%
|
APTT: To High |
2
200%
|
0
0%
|
1
50%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
2
66.7%
|
Basophil count: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Basophil count: To Normal or NC |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
5
250%
|
12
300%
|
6
600%
|
6
200%
|
Basophil count: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
Eosinophil count: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Eosinophil count: To Normal or NC |
21
2100%
|
5
250%
|
3
150%
|
6
300%
|
5
250%
|
12
300%
|
6
600%
|
5
166.7%
|
Eosinophil count: To High |
2
200%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
1
33.3%
|
Fibrinogen: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Fibrinogen: To Normal or NC |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
5
166.7%
|
Fibrinogen: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
MCH: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCH: To Normal or NC |
23
2300%
|
4
200%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
MCH: To High |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCV: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCV: To Normal or NC |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
MCV: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Monocyte count: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Monocyte count: To Normal or NC |
19
1900%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
6
150%
|
6
600%
|
6
200%
|
Monocyte count: To High |
4
400%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
6
150%
|
0
0%
|
0
0%
|
PT: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
PT: To Normal or NC |
23
2300%
|
5
250%
|
2
100%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
5
166.7%
|
PT: To High |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
RBC: To Low |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
RBC: To Normal or NC |
22
2200%
|
5
250%
|
2
100%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
RBC: To High |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Reticulocyte count: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Reticulocyte count: To Normal or NC |
23
2300%
|
4
200%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Reticulocyte count: To High |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were planned to be collected to analyze hematology parameters. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were planned to be collected to analyze hematology parameters. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
Hematocrit: To Low |
0
0%
|
0
0%
|
|||
Hematocrit: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Hematocrit: To High |
0
0%
|
0
0%
|
|||
Hemoglobin: To Low |
0
0%
|
0
0%
|
|||
Hemoglobin: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Hemoglobin: To High |
0
0%
|
0
0%
|
|||
Lymphocyte count: To Low |
1
100%
|
0
0%
|
|||
Lymphocyte count: To within Range or No Change |
10
1000%
|
14
700%
|
|||
Lymphocyte count: To High |
0
0%
|
0
0%
|
|||
Platelet count: To Low |
0
0%
|
0
0%
|
|||
Platelet count: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Platelet count: To High |
0
0%
|
0
0%
|
|||
Total ANC: To Low |
1
100%
|
0
0%
|
|||
Total ANC: To within Range or No Change |
10
1000%
|
14
700%
|
|||
Total ANC: To High |
0
0%
|
0
0%
|
|||
WBC: To Low |
1
100%
|
1
50%
|
|||
WBC: To within Range or No Change |
10
1000%
|
13
650%
|
|||
WBC: To High |
0
0%
|
0
0%
|
Title | Part C: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
APTT: To Low |
1
100%
|
0
0%
|
|||
APTT: To Normal or NC |
10
1000%
|
13
650%
|
|||
APTT: To High |
0
0%
|
1
50%
|
|||
Basophil count: To Low |
0
0%
|
0
0%
|
|||
Basophil count: To Normal or NC |
11
1100%
|
14
700%
|
|||
Basophil count: To High |
0
0%
|
0
0%
|
|||
Eosinophil count: To Low |
0
0%
|
0
0%
|
|||
Eosinophil count: To Normal or NC |
11
1100%
|
14
700%
|
|||
Eosinophil count: To High |
0
0%
|
0
0%
|
|||
Fibrinogen: To Low |
0
0%
|
0
0%
|
|||
Fibrinogen: To Normal or NC |
11
1100%
|
14
700%
|
|||
Fibrinogen: To High |
0
0%
|
0
0%
|
|||
MCH: To Low |
0
0%
|
0
0%
|
|||
MCH: To Normal or NC |
11
1100%
|
14
700%
|
|||
MCH: To High |
0
0%
|
0
0%
|
|||
MCV: To Low |
0
0%
|
0
0%
|
|||
MCV: To Normal or NC |
11
1100%
|
14
700%
|
|||
MCV: To High |
0
0%
|
0
0%
|
|||
Monocyte count: To Low |
0
0%
|
0
0%
|
|||
Monocyte count: To Normal or NC |
11
1100%
|
14
700%
|
|||
Monocyte count: To High |
0
0%
|
0
0%
|
|||
PT: To Low |
0
0%
|
0
0%
|
|||
PT: To Normal or NC |
10
1000%
|
14
700%
|
|||
PT: To High |
1
100%
|
0
0%
|
|||
RBC: To Low |
0
0%
|
1
50%
|
|||
RBC: To Normal or NC |
11
1100%
|
13
650%
|
|||
RBC: To High |
0
0%
|
0
0%
|
|||
Reticulocyte count: To Low |
0
0%
|
0
0%
|
|||
Reticulocyte count: To Normal or NC |
11
1100%
|
14
700%
|
|||
Reticulocyte count: To High |
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Abnormal Urinalysis Parameters |
---|---|
Description | 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. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
RBC |
2
200%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
WBC |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
Cellular casts |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Granular casts |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hyaline casts |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With Abnormal Urinalysis Parameters |
---|---|
Description | Urine samples were planned to be collected to analyze urine parameters. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With Abnormal Urinalysis Parameters |
---|---|
Description | 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. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
RBC |
0
0%
|
0
0%
|
|||
WBC |
1
100%
|
1
50%
|
|||
Cellular casts |
0
0%
|
0
0%
|
|||
Granular casts |
0
0%
|
0
0%
|
|||
Hyaline casts |
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
SBP: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
SBP: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
SBP: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
DBP: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
DBP: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
DBP: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Heart rate: To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Heart rate: To within Range or No Change |
23
2300%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
12
300%
|
6
600%
|
6
200%
|
Heart rate: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Respiratory rate: To Low |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
Respiratory rate: To within Range or No Change |
22
2200%
|
5
250%
|
3
150%
|
6
300%
|
6
300%
|
11
275%
|
6
600%
|
6
200%
|
Respiratory rate: To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Body temperature: To Low |
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Body temperature: To within Range or No Change |
22
2200%
|
5
250%
|
3
150%
|
5
250%
|
6
300%
|
11
275%
|
6
600%
|
6
200%
|
Body temperature: To High |
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline |
---|---|
Description | 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%. |
Time Frame | Up to Day 49 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
SBP: To Low |
0
0%
|
0
0%
|
|||
SBP: To within Range or No Change |
11
1100%
|
14
700%
|
|||
SBP: To High |
0
0%
|
0
0%
|
|||
DBP: To Low |
0
0%
|
0
0%
|
|||
DBP: To within Range or No Change |
11
1100%
|
14
700%
|
|||
DBP: To High |
0
0%
|
0
0%
|
|||
Heart rate: To Low |
0
0%
|
1
50%
|
|||
Heart rate: To within Range or No Change |
10
1000%
|
13
650%
|
|||
Heart rate: To High |
1
100%
|
0
0%
|
|||
Respiratory rate: To Low |
1
100%
|
1
50%
|
|||
Respiratory rate: To within Range or No Change |
9
900%
|
13
650%
|
|||
Respiratory rate: To High |
1
100%
|
0
0%
|
|||
Body temperature: To Low |
0
0%
|
0
0%
|
|||
Body temperature: To within Range or No Change |
11
1100%
|
14
700%
|
|||
Body temperature: To High |
0
0%
|
0
0%
|
Title | Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings |
---|---|
Description | 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. |
Time Frame | Up to Day 193 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Abnormal - not clinically significant |
6
600%
|
1
50%
|
0
0%
|
0
0%
|
3
150%
|
2
50%
|
3
300%
|
0
0%
|
Abnormal - clinically significant |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings |
---|---|
Description | Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF. |
Time Frame | Up to Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings |
---|---|
Description | 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. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected for Cohorts 6 to 8 as no participants were enrolled. |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
Abnormal - not clinically significant |
2
200%
|
3
150%
|
|||
Abnormal - clinically significant |
0
0%
|
1
50%
|
Title | Part A: Plasma Concentrations of GSK3358699 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Pre-dose, n=5,3,6,6,12,6,6 |
0.0000
|
0.0000
|
0.0000
|
0.0000
|
0.0000
|
0.0000
|
0.0000
|
15 minutes, n=5,3,6,6,12,6,6 |
0.4950
|
0.6470
|
1.0480
|
0.5390
|
0.2620
|
5.8460
|
0.9245
|
30 minutes, n=5,3,6,6,12,6,6 |
0.6840
|
1.9510
|
6.4560
|
5.1050
|
5.9130
|
64.4810
|
33.2120
|
1 hour, n=5,3,6,6,12,6,6 |
0.4210
|
0.9960
|
3.5150
|
9.1840
|
11.0785
|
28.4500
|
28.8380
|
2 hours, n=5,3,6,6,12,6,6 |
0.1810
|
0.4790
|
1.6930
|
4.8100
|
6.9495
|
10.6550
|
8.6735
|
4 hours, n=5,2,6,6,12,6,6 |
NA
|
0.1560
|
0.5265
|
1.2865
|
1.9095
|
3.6390
|
2.5920
|
6 hours, n=5,3,6,6,12,6,6 |
NA
|
NA
|
0.3160
|
0.6720
|
1.1020
|
1.4305
|
1.2515
|
8 hours, n=5,3,6,6,12,6,6 |
NA
|
NA
|
0.2120
|
0.3775
|
0.5915
|
0.8340
|
0.6665
|
12 hours, n=5,3,2,6,12,6,6 |
NA
|
NA
|
0.1390
|
0.1490
|
0.2510
|
0.5195
|
0.4255
|
24 hours, n=5,3,6,6,9,4,5 |
NA
|
NA
|
NA
|
NA
|
0.1510
|
0.1250
|
0.2090
|
48 hours, n=5,3,6,6,6,6,6 |
NA
|
NA
|
NA
|
NA
|
0.0000
|
NA
|
NA
|
Title | Part B: Plasma Concentrations of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Plasma Concentrations of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1:Pre-dose,n=14,0,0,0 |
0.0000
|
|||
Day 1:15 minutes,n=14,0,0,0 |
0.2825
|
|||
Day 1:30 minutes,n=14,0,0,0 |
5.7430
|
|||
Day 1:1 hour,n=14,0,0,0 |
3.8955
|
|||
Day 1:2 hours,n=14,0,0,0 |
1.3365
|
|||
Day 1:4 hours,n=14,0,0,0 |
0.5730
|
|||
Day 1:6 hours,n=14,0,0,0 |
0.2940
|
|||
Day 1:8 hours,n=10,0,0,0 |
0.1690
|
|||
Day 1:12 hours,n=3,0,0,0 |
0.1390
|
|||
Day 1:24 hours,n=14,0,0,0 |
NA
|
|||
Day 4: Pre-dose,n=1,0,0,0 |
0.0000
|
|||
Day 8: Pre-dose,n=2,0,0,0 |
0.0000
|
|||
Day 12: Pre-dose,n=4,0,0,0 |
NA
|
|||
Day 14:Pre-dose,n=2,0,0,0 |
NA
|
|||
Day 14:15 minutes,n=2,0,0,0 |
4.3390
|
|||
Day 14:30 minutes,n=2,0,0,0 |
6.0065
|
|||
Day 14:1 hour,n=2,0,0,0 |
3.0170
|
|||
Day 14:2 hours,n=2,0,0,0 |
1.4905
|
|||
Day 14:4 hours,n=2,0,0,0 |
0.8295
|
|||
Day 14:6 hours,n=2,0,0,0 |
0.6360
|
|||
Day 14:8 hours,n=2,0,0,0 |
0.3920
|
|||
Day 14:12 hours,n=1,0,0,0 |
0.2730
|
|||
Day 14:24 hours,n=2,0,0,0 |
NA
|
|||
Day 14:48 hours,n=2,0,0,0 |
NA
|
Title | Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Hours*nanogram per milliliter] |
0.74
|
2.33
|
10.77
|
23.40
|
31.88
|
66.38
|
58.09
|
Title | Part B: AUC(0-t) of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-t) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
9.47
|
|||
Day 14, n=2,0,0,0 |
11.70
|
Title | Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 5 | 6 | 9 | 4 | 5 |
Median (Full Range) [Hours*nanogram per milliliter] |
NA
|
NA
|
13.20
|
23.89
|
33.22
|
69.13
|
59.68
|
Title | Part B: AUC(0-infinity) of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-infinity) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 7 | 0 | 0 | 0 |
Day 1, n=7,0,0,0 |
9.07
|
Title | Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 5 | 6 | 10 | 5 | 6 |
Median (Full Range) [Hours*nanogram per milliliter] |
NA
|
NA
|
13.17
|
23.86
|
32.69
|
67.38
|
59.05
|
Title | Part B: AUC(0-24) of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-24) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 7 | 0 | 0 | 0 |
Day 1, n=7,0,0,0 |
9.07
|
|||
Day 14, n=1,0,0,0 |
7.99
|
Title | Part A: Maximum Plasma Concentration (Cmax) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Nanogram per milliliter] |
0.68
|
1.95
|
6.46
|
16.10
|
17.47
|
64.48
|
34.58
|
Title | Part B: Cmax of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Cmax of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
6.19
|
|||
Day 14, n=2,0,0,0 |
6.01
|
Title | Part A: Time to Cmax (Tmax) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Hours] |
0.50
|
0.50
|
0.50
|
1.00
|
1.00
|
0.76
|
0.51
|
Title | Part B: Tmax of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Tmax of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
0.50
|
|||
Day 14, n=2,0,0,0 |
0.53
|
Title | Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 5 | 6 | 9 | 4 | 5 |
Median (Full Range) [Hours] |
NA
|
NA
|
2.44
|
2.75
|
6.02
|
4.77
|
6.88
|
Title | Part B: t1/2 of GSK3358699 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: t1/2 of GSK3358699 |
---|---|
Description | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 7 | 0 | 0 | 0 |
Day 1, n=7,0,0,0 |
2.47
|
|||
Day 14, n=1,0,0,0 |
1.57
|
Title | Part A: Plasma Concentrations of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Pre-dose |
0.0000
|
0.000
|
0.0000
|
0.0000
|
0.0000
|
0.0000
|
0.0000
|
15 minutes |
0.2050
|
0.2070
|
0.0550
|
0.0000
|
0.0000
|
0.0575
|
0.0000
|
30 minutes |
1.2090
|
1.8410
|
3.1930
|
1.8370
|
4.3810
|
17.2245
|
6.3350
|
1 hour |
3.0310
|
4.2200
|
17.1455
|
26.1280
|
33.6145
|
89.1965
|
74.5130
|
2 hours |
3.2830
|
5.5640
|
17.6535
|
46.4250
|
70.4010
|
102.0865
|
121.2220
|
4 hours |
1.9110
|
3.2490
|
10.6790
|
22.6925
|
46.8165
|
51.7230
|
69.2315
|
6 hours |
0.9490
|
1.5760
|
6.7745
|
13.7955
|
23.1275
|
30.4690
|
36.8305
|
8 hours |
0.5840
|
1.0200
|
4.6515
|
8.3535
|
13.7165
|
16.5795
|
18.4825
|
12 hours |
0.2540
|
0.4670
|
1.8400
|
3.4535
|
5.3830
|
6.7365
|
8.7280
|
24 hours |
0.0000
|
0.1050
|
0.2620
|
0.4790
|
1.2020
|
1.1015
|
1.5040
|
48 hours |
NA
|
NA
|
0.0000
|
0.0000
|
0.3440
|
0.1895
|
0.2565
|
Title | Part B: Plasma Concentrations of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Plasma Concentrations of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1:Pre-dose,n=14,0,0,0 |
0.0000
|
|||
Day 1:15 minutes,n=14,0,0,0 |
0.0000
|
|||
Day 1:30 minutes,n=14,0,0,0 |
3.1310
|
|||
Day 1:1 hour,n=14,0,0,0 |
19.9335
|
|||
Day 1:2 hours,n=14,0,0,0 |
22.2250
|
|||
Day 1:4 hours,n=14,0,0,0 |
12.7730
|
|||
Day 1:6 hours,n=14,0,0,0 |
7.2920
|
|||
Day 1:8 hours,n=14,0,0,0 |
4.3750
|
|||
Day 1:12 hours,n=14,0,0,0 |
2.2070
|
|||
Day 1:24 hours,n=14,0,0,0 |
0.3805
|
|||
Day 4: Pre-dose,n=14,0,0,0 |
0.5355
|
|||
Day 8: Pre-dose,n=7,0,0,0 |
0.6640
|
|||
Day 12: Pre-dose,n=4,0,0,0 |
0.4945
|
|||
Day 14:Pre-dose,n=2,0,0,0 |
0.5820
|
|||
Day 14:15 minutes,n=2,0,0,0 |
0.7430
|
|||
Day 14:30 minutes,n=2,0,0,0 |
6.4130
|
|||
Day 14:1 hour,n=2,0,0,0 |
15.3355
|
|||
Day 14:2 hours,n=2,0,0,0 |
15.0925
|
|||
Day 14:4 hours,n=2,0,0,0 |
10.4550
|
|||
Day 14:6 hours,n=2,0,0,0 |
6.8500
|
|||
Day 14:8 hours,n=2,0,0,0 |
6.0330
|
|||
Day 14:12 hours,n=2,0,0,0 |
2.2290
|
|||
Day 14:24 hours,n=2,0,0,0 |
0.5275
|
|||
Day 14:48 hours,n=1,0,0,0 |
0.1110
|
Title | Part A: AUC(0-t) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Hours*nanogram per milliliter] |
15.16
|
29.12
|
106.55
|
209.98
|
381.16
|
470.40
|
630.63
|
Title | Part B: AUC(0-t) of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-t) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
115.17
|
|||
Day 14, n=2,0,0,0 |
109.71
|
Title | Part A: AUC(0-infinity) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 2 | 2 | 6 | 4 | 8 | 4 | 6 |
Median (Full Range) [Hours*nanogram per milliliter] |
17.08
|
29.05
|
108.29
|
189.02
|
357.98
|
492.92
|
649.74
|
Title | Part B: AUC(0-infinity) of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-infinity) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
117.25
|
Title | Part A: AUC(0-24) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 2 | 2 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Hours*nanogram per milliliter] |
16.44
|
28.27
|
106.55
|
209.96
|
374.49
|
452.66
|
586.70
|
Title | Part B: AUC(0-24) of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: AUC(0-24) of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
115.31
|
|||
Day 14, n=2,0,0,0 |
106.19
|
Title | Part A: Cmax of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Nanogram per milliliter] |
3.28
|
6.03
|
19.39
|
50.13
|
71.67
|
102.09
|
121.22
|
Title | Part B: Cmax of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Cmax of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
23.02
|
|||
Day 14, n=2,0,0,0 |
15.34
|
Title | Part A: Tmax of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Median (Full Range) [Hours] |
1.00
|
2.00
|
2.00
|
2.01
|
2.00
|
2.00
|
2.00
|
Title | Part B: Tmax of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Tmax of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
2.00
|
|||
Day 14, n=2,0,0,0 |
0.99
|
Title | Part A: t1/2 of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Only those participants with data available at the specified time points were analyzed. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 2 | 2 | 6 | 4 | 8 | 4 | 6 |
Median (Full Range) [Hours] |
4.97
|
4.91
|
4.10
|
3.80
|
7.81
|
6.98
|
6.76
|
Title | Part B: t1/2 of GSK3206944 |
---|---|
Description | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: t1/2 of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1, n=14,0,0,0 |
5.02
|
|||
Day 14, n=2,0,0,0 |
6.15
|
Title | Part A: Monocyte Intracellular Concentration of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. |
Arm/Group Title | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
Day 1: 1 hour |
NA
|
NA
|
0.177
|
0.673
|
NA
|
1.243
|
1.410
|
Day 1: 4 hours |
NA
|
NA
|
NA
|
0.105
|
0.149
|
0.277
|
0.297
|
Day 1: 8 hours |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Day 1: 24 hours |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Day 1: 48 hours |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Title | Part B: Monocyte Intracellular Concentration of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period |
Outcome Measure Data
Analysis Population Description |
---|
PK Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Monocyte Intracellular Concentration of GSK3206944 |
---|---|
Description | 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. |
Time Frame | Days 1 and 13: 1, 4 and 8 hour; Days 4, 8 and 12: Pre-dose; Day 14: 1, 4, 8, 24 and 48 hours post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
---|---|---|---|---|
Arm/Group Description | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 14 | 0 | 0 | 0 |
Day 1: 1 hour,n=14,0,0,0 |
0.313
|
|||
Day 1: 4 hours,n=14,0,0,0 |
NA
|
|||
Day 1: 8 hours,n=14,0,0,0 |
NA
|
|||
Day 4: Pre-dose,n=14,0,0,0 |
NA
|
|||
Day 8: Pre-dose,n=14,0,0,0 |
NA
|
|||
Day 12: Pre-dose,n=14,0,0,0 |
NA
|
|||
Day 13: 1 hour,n=1,0,0,0 |
0.317
|
|||
Day 13: 4 hours,n=1,0,0,0 |
NA
|
|||
Day 13: 8 hours,n=1,0,0,0 |
NA
|
|||
Day 14: 1 hour,n=1,0,0,0 |
0.256
|
|||
Day 14: 4 hours,n=1,0,0,0 |
NA
|
|||
Day 14: 8 hours,n=1,0,0,0 |
NA
|
|||
Day 14: 24 hours,n=1,0,0,0 |
NA
|
|||
Day 14: 48 hours,n=1,0,0,0 |
NA
|
Title | 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 |
---|---|
Description | 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. |
Time Frame | Day 1: 1, 4, 8, 12, 24 and 48 hours |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. |
Measure Participants | 17 | 5 | 3 | 6 | 6 | 0 | 6 | 6 |
Day 1: IL6, 1 hour, n=17,5,3,6,6,0,6,6 |
10352.87
|
15208.12
|
20385.25
|
12820.72
|
15596.95
|
10057.64
|
5728.17
|
|
Day 1: IL6, 4 hours, n=17,5,3,6,6,0,6,6 |
13092.01
|
13851.61
|
19431.61
|
15636.75
|
12900.07
|
12074.28
|
7544.02
|
|
Day 1: IL6, 8 hours, n=17,5,3,6,6,0,6,6 |
12560.83
|
13629.60
|
28805.81
|
16564.79
|
17019.48
|
16486.96
|
8688.63
|
|
Day 1: IL6, 12 hour, n=17,5,3,6,6,0,6,6 |
15125.82
|
13890.39
|
28948.13
|
18712.82
|
15622.25
|
12305.88
|
6754.46
|
|
Day 1: IL6, 24 hours, n=17,5,3,6,6,0,6,6 |
12876.74
|
16961.79
|
23634.22
|
14387.39
|
12593.53
|
12894.02
|
8705.59
|
|
Day 1: IL6, 48 hours, n=17,5,3,6,6,0,6,6 |
13204.84
|
16209.14
|
27160.99
|
14786.71
|
13685.44
|
14374.44
|
8359.81
|
|
Day 1: MCP-1, 1 hour, n=17,5,2,6,6,0,6,6 |
2107.38
|
2997.62
|
2539.15
|
1273.19
|
1278.42
|
1604.85
|
1047.32
|
|
Day 1: MCP-1, 4 hours, n=17,5,3,6,6,0,6,6 |
1748.71
|
2638.95
|
3774.02
|
1410.01
|
1648.51
|
2604.00
|
1643.37
|
|
Day 1: MCP-1, 8 hours, n=17,5,3,6,6,0,6,6 |
1300.34
|
2911.87
|
3145.66
|
1606.85
|
1533.33
|
2312.12
|
1863.25
|
|
Day 1: MCP-1, 12 hour, n=17,5,3,6,6,0,6,6 |
1791.07
|
2738.20
|
3048.56
|
2003.41
|
1297.53
|
2062.41
|
2270.49
|
|
Day 1: MCP-1, 24 hours, n=17,5,3,6,6,0,6,6 |
1662.28
|
2349.62
|
2216.41
|
1691.59
|
1062.86
|
2275.17
|
1988.64
|
|
Day 1: MCP-1, 48 hours, n=17,5,3,6,6,0,6,6 |
1398.36
|
2306.83
|
1621.46
|
1729.87
|
1200.15
|
1595.51
|
1828.23
|
|
Day 1: TNF alpha, 1 hour, n=17,5,3,6,6,0,6,6 |
2525.78
|
2281.20
|
4340.00
|
3455.53
|
3916.76
|
1971.77
|
1552.10
|
|
Day 1: TNF alpha, 4 hours, n=17,5,3,6,6,0,6,6 |
3189.81
|
3452.27
|
3381.52
|
4493.55
|
2672.58
|
3618.72
|
1876.55
|
|
Day 1: TNF alpha, 8 hours, n=17,5,3,6,6,0,6,6 |
3673.78
|
3630.47
|
9631.19
|
4612.79
|
4908.42
|
5233.22
|
2934.21
|
|
Day 1: TNF alpha, 12 hour, n=17,5,3,6,6,0,6,6 |
4206.18
|
3680.34
|
8736.93
|
5139.53
|
3079.37
|
2846.57
|
1729.42
|
|
Day 1: TNF alpha, 24 hours, n=17,5,3,5,6,0,6,6 |
3164.79
|
4528.14
|
4694.58
|
5576.01
|
3543.62
|
3649.08
|
2741.96
|
|
Day 1: TNF alpha, 48 hours, n=17,5,3,6,6,0,6,6 |
3445.95
|
4077.77
|
10364.95
|
4186.10
|
3963.40
|
3788.04
|
2404.11
|
Title | Part B: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation |
---|---|
Description | 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. |
Time Frame | Day 1: 1, 4, 8, 12, 24 and 48 hours |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Data was not collected as no participants were enrolled in Part B. |
Arm/Group Title | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 0 | 0 |
Title | Part C: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation |
---|---|
Description | 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. |
Time Frame | Day 1: 1, 4 and 8 hours; Days 2, 4, 8 and 12: Pre-dose; Day 13: Pre-dose, 1, 4 and 8 hours; Day 14: Pre-dose, Pre-LPS challenge, 1, 4, 8, 24 and 48 hours |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
---|---|---|---|---|---|
Arm/Group Description | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). |
Measure Participants | 11 | 14 | 0 | 0 | 0 |
IL6:Day 1,1 hour,n=11,13,0,0,0 |
9488.65
|
9629.75
|
|||
IL6:Day 1,4 hours,n=11,14,0,0,0 |
9121.35
|
10686.75
|
|||
IL6:Day 1,8 hours,n=11,14,0,0,0 |
13079.21
|
15475.58
|
|||
IL6:Day 2,Pre-dose,n=11,14,0,0,0 |
9323.67
|
12396.71
|
|||
IL6:Day 4,Pre-dose,n=11,14,0,0,0 |
11002.47
|
12558.78
|
|||
IL6:Day 8,Pre-dose,n=6,7,0,0,0 |
11305.84
|
10766.02
|
|||
IL6:Day 12,Pre-dose,n=5,4,0,0,0 |
9329.36
|
10539.82
|
|||
IL6:Day 13,Pre-dose,n=1,1,0,0,0 |
9966.64
|
12743.26
|
|||
IL6:Day 13,1 hour,n=1,1,0,0,0 |
11718.40
|
12508.94
|
|||
IL6:Day 13,4 hours,n=1,1,0,0,0 |
7099.42
|
11616.53
|
|||
IL6:Day 13,8 hours,n=1,1,0,0,0 |
10722.24
|
16723.58
|
|||
IL6:Day 14,Pre-dose,n=1,1,0,0,0 |
8918.96
|
14654.83
|
|||
IL6:Day 14,Pre LPS challenge,n=1,1,0,0,0 |
8696.65
|
11340.79
|
|||
IL6:Day 14,1 hour,n=1,1,0,0,0 |
10082.23
|
13244.20
|
|||
IL6:Day 14,4 hours,n=1,1,0,0,0 |
9122.21
|
11543.08
|
|||
IL6:Day 14,8 hours,n=1,1,0,0,0 |
10986.16
|
12544.55
|
|||
IL6:Day 14,24 hours,n=1,1,0,0,0 |
9176.89
|
9114.15
|
|||
IL6:Day 14,48 hours,n=1,1,0,0,0 |
8257.88
|
10304.01
|
|||
MCP-1:Day 1,1 hour,n=11,14,0,0,0 |
1739.49
|
2216.06
|
|||
MCP-1:Day 1,4 hours,n=11,14,0,0,0 |
1825.09
|
2405.11
|
|||
MCP-1:Day 1,8 hours,n=11,14,0,0,0 |
2002.44
|
2044.64
|
|||
MCP-1:Day 2,Pre-dose,n=11,14,0,0,0 |
1939.09
|
1928.51
|
|||
MCP-1:Day 4,Pre-dose,n=11,14,0,0,0 |
1677.88
|
1939.65
|
|||
MCP-1:Day 8,Pre-dose,n=6,7,0,0,0 |
1638.33
|
1719.26
|
|||
MCP-1:Day 12,Pre-dose,n=5,4,0,0,0 |
1799.12
|
2176.12
|
|||
MCP-1:Day 13,Pre-dose,n=1,1,0,0,0 |
1839.00
|
513.36
|
|||
MCP-1:Day 13,1 hour,n=1,1,0,0,0 |
2113.92
|
294.72
|
|||
MCP-1:Day 13,4 hours,n=1,1,0,0,0 |
1872.12
|
890.77
|
|||
MCP-1:Day 13,8 hours,n=1,1,0,0,0 |
1997.87
|
1412.52
|
|||
MCP-1:Day 14,Pre-dose,n=1,1,0,0,0 |
2007.09
|
4935.03
|
|||
MCP-1:Day 14,Pre LPS challenge,n=1,1,0,0,0 |
1876.05
|
1981.15
|
|||
MCP-1:Day 14,1 hour,n=1,1,0,0,0 |
3503.11
|
3623.79
|
|||
MCP-1:Day 14,4 hours,n=1,1,0,0,0 |
2066.72
|
3293.92
|
|||
MCP-1:Day 14,8 hours,n=1,1,0,0,0 |
2593.90
|
3150.84
|
|||
MCP-1:Day 14,24 hours,n=1,1,0,0,0 |
2082.28
|
3372.94
|
|||
MCP-1:Day 14,48 hours,n=1,1,0,0,0 |
1879.53
|
2715.94
|
|||
TNF alpha:Day 1,1 hour,n=11,13,0,0,0 |
1994.72
|
2078.66
|
|||
TNF alpha:Day 1,4 hours,n=11,14,0,0,0 |
1843.08
|
2297.36
|
|||
TNF alpha:Day 1,8 hours,n=11,14,0,0,0 |
3692.36
|
3854.86
|
|||
TNF alpha:Day 2,Pre-dose,n=11,14,0,0,0 |
2711.07
|
3028.33
|
|||
TNF alpha:Day 4,Pre-dose,n=11,14,0,0,0 |
2987.24
|
3045.05
|
|||
TNF alpha:Day 8,Pre-dose,n=6,7,0,0,0 |
2932.72
|
2849.52
|
|||
TNF alpha:Day 12,Pre-dose,n=5,4,0,0,0 |
2482.03
|
2407.60
|
|||
TNF alpha:Day 13,Pre-dose,n=1,1,0,0,0 |
2311.66
|
2995.36
|
|||
TNF alpha:Day 13,1 hour,n=1,1,0,0,0 |
3495.21
|
2648.27
|
|||
TNF alpha:Day 13,4 hours,n=1,1,0,0,0 |
1573.18
|
2815.39
|
|||
TNF alpha:Day 13,8 hours,n=1,1,0,0,0 |
2486.89
|
4472.25
|
|||
TNF alpha:Day 14,Pre-dose,n=1,1,0,0,0 |
2304.40
|
3327.69
|
|||
TNF alpha:Day 14,Pre LPS challenge,n=1,1,0,0,0 |
2092.07
|
2081.54
|
|||
TNF alpha:Day 14,1 hour,n=1,1,0,0,0 |
2103.62
|
3133.32
|
|||
TNF alpha:Day 14,4 hours,n=1,1,0,0,0 |
1771.69
|
2457.35
|
|||
TNF alpha:Day 14,8 hours,n=1,1,0,0,0 |
2560.84
|
3481.91
|
|||
TNF alpha:Day 14,24 hours,n=1,1,0,0,0 |
1482.94
|
2187.40
|
|||
TNF alpha:Day 14,48 hours,n=1,1,0,0,0 |
1909.65
|
2597.32
|
Adverse Events
Time Frame | Up to Day 193 in Part A and up to Day 49 in Part C (Cohorts 4 and 5) | |||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety Population.All-cause mortality,non-SAEs and SAEs were not collected in Part B and Part C(Cohorts 6 to 8) as no participants were enrolled.Data is presented for Part A and Part C(Cohorts4 and 5) only as data was not collected in Part B and Part C(Cohorts6 to 8) due to study termination and Part B and Part C(Cohorts 6 to 8) were not initiated. | |||||||||||||||||||||||||||||
Arm/Group Title | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | |||||||||||||||
Arm/Group Description | 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. | Participants in Part A received a SD of GSK3358699 1 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 3 mg on Day 1 in treatment Period 1. | Participants in Part A received a SD of GSK3358699 10 mg on Day 1 in treatment Period 2. | Participants in Part A received a SD of GSK3358699 20 mg on Day 1 in treatment Period 2. | 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. | Participants in Part A received a SD of GSK3358699 30 mg on Day 1 in treatment Period 3. | Participants in Part A received a SD of GSK3358699 40 mg on Day 1 in treatment Period 3. | 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. | 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. | 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). | 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). | Participants in Part C Cohort 6 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 7 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. | Participants in Part C Cohort 8 were planned to receive once daily repeat dose of GSK3358699 or placebo on Days 1 to 14. On Day 14, participants were planned to receive an IV in vivo LPS challenge at a dose of 0.75 ng/kg or an IV infusion of GM-CSF, in vivo as 60 mcg/m^2. The administration of LPS or GM-CSF was planned to be followed by blister induction on forearm (0.2% cantharidin). | |||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||
Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | ||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/23 (0%) | 0/5 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/6 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/11 (0%) | 0/14 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||
Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | ||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/23 (0%) | 0/5 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/6 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/11 (0%) | 1/14 (7.1%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||||||||||||
Cardiac disorders | ||||||||||||||||||||||||||||||
Atrial fibrillation | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Other (Not Including Serious) Adverse Events |
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Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | ||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/23 (17.4%) | 2/5 (40%) | 3/3 (100%) | 2/6 (33.3%) | 3/6 (50%) | 8/12 (66.7%) | 4/6 (66.7%) | 3/6 (50%) | 0/0 (NaN) | 0/0 (NaN) | 7/11 (63.6%) | 7/14 (50%) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | |||||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||
Neutropenia | 0/23 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Cardiac disorders | ||||||||||||||||||||||||||||||
Palpitations | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Sinus tachycardia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Tachycardia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 2 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Atrial fibrillation | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Atrial tachycardia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Ventricular extrasystoles | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Ventricular tachycardia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Eye disorders | ||||||||||||||||||||||||||||||
Ocular hyperaemia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Keratitis | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||||||||
Abdominal pain upper | 1/23 (4.3%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Diarrhoea | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Dyspepsia | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Nausea | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
General disorders | ||||||||||||||||||||||||||||||
Feeling cold | 1/23 (4.3%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Feeling hot | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Malaise | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Pain | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Pyrexia | 1/23 (4.3%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Infections and infestations | ||||||||||||||||||||||||||||||
Hordeolum | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Nasopharyngitis | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Urinary tract infection | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Folliculitis | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||
Arthropod bite | 1/23 (4.3%) | 2 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Contusion | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Head injury | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Investigations | ||||||||||||||||||||||||||||||
Alanine aminotransferase increased | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||
Back pain | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Nervous system disorders | ||||||||||||||||||||||||||||||
Headache | 2/23 (8.7%) | 2 | 1/5 (20%) | 3 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 3 | 2/6 (33.3%) | 2 | 4/12 (33.3%) | 4 | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 2 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 2/11 (18.2%) | 2 | 2/14 (14.3%) | 2 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Renal and urinary disorders | ||||||||||||||||||||||||||||||
Renal atrophy | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||
Oropharyngeal pain | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Rhinorrhoea | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Throat irritation | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Productive cough | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||
Dermatitis contact | 0/23 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title | GSK Response Center |
---|---|
Organization | GlaxoSmithKline |
Phone | 866-435-7343 |
GSKClinicalSupportHD@gsk.com |
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