Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects

Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Safety Population consisted of all randomized participants who received at least one dose of study treatment.

Time frame: Up to Week 12

Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.

Time frame: Up to Week 9

Part B: Number of Participants With Non-SAEs and SAEs

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

PCI ranges were \<0.0 or \>0.1\*10\^9 cells per(/)liter(L)(basophils), \<37 or \>50 proportion of red blood cells(RBC) in blood(hematocrit),\<130 or \>170 grams/L(hemoglobin\[Hb\]), \<1.2 or \>3.65\*10\^9cells(c)/L (lymphocytes),\<0.2 or \>1\*10\^9c/L(monocytes), \<2 or \>7.5\*10\^9c/L(neutrophils), \<150 or \>400\*10\^9 c/L(platelets), \<3.0 or \>10\*10\^9c/L(white blood cell\[WBC\]count), \<4.4 or \>5.8\*10\^12 c/L(RBC count), \<80 or \>99 femtoliter(mean corpuscular\[MC\] volume), \<26.0 or \>33.5 picogram(MC Hb), \<0.0 or \>0.4\*10\^9 c/L(eosinophils). 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 percentage(%).

Time frame: Up to Week 12

Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline

Blood samples were planned to be collected to analyze hematology parameters.

Time frame: Up to Week 9

Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline

Blood samples were planned to be collected to analyze hematology parameters.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

PCI ranges were \<34 or \>50 grams/L(albumin),\<40 or \>129 international units/L\[IU/L\](alkaline phosphatase),\<10 or \>50 IU/L(alanine aminotransferase),\<0 or \>37(aspartate aminotransferase), \<0 or \>20 micromoles(mcmol)/L (direct bilirubin),\<0 or \>20 mcmol/L(bilirubin), \<2.2 or \>2.6 millimoles/L(mmol/L)(calcium),\<66 or \>112 upper limit of normal mmol/L(creatinine), \<3.5 or \>5.1 mmol/L (potassium),\<0.6 or \>1 mmol/L (magnesium),\<0.87 or \>1.45mmol/L (phosphate),\<63 or \>83 g/L (protein),\<135 or \>145 mmol/L (sodium), \<0.0 or \>5.0 mg/L (C-reactive protein). Participants were counted in worst case category that their value changes to(low, within range \[WR\] or no change\[NC\] 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 WR, were recorded in To WR 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 Week 12

Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were planned to be collected to analyze chemistry parameters.

Time frame: Up to Week 9

Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were planned to be collected to analyze chemistry parameters.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Urine samples were collected for analysis of occult blood, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood and protein can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

Time frame: Up to Week 12

Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Urine samples were planned to be collected to analyze urine parameters.

Time frame: Up to Week 9

Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Urine samples were planned to be collected to analyze urine parameters.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT 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 Week 12

Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings

Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.

Time frame: Up to Week 9

Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings

Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline

Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse 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), pulse rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute): \<10(low) or \>25(high) and body temperature (degrees Celsius) \<35 (low) or \>38 (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 Week 12

Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline

Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.

Time frame: Up to Week 9

Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline

Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.

Time frame: Up to Week 9

Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings

Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Abnormal findings were categorized as CS and not NCS. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Time frame: Up to 24 hours post-dose

Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings

Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.

Time frame: Up to 24 hours post-dose

Part B: Number of Participants Abnormal Cardiac Telemetry Findings

Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.

Time frame: Up to 24 hours post-dose