Leishmaniasis
Conditions
Keywords
Dose escalation phase, First time in human, Single ascending dose, Multiple ascending dose, GSK3186899
Brief summary
The purpose of this study is to evaluate the safety, tolerability and PK profile of single and repeat ascending doses of GSK3186899 in healthy subjects. This is a Phase 1 first time in human study, to investigate the effect of food on PK of GSK3186899. This study will consists of two parts. Part A (dose escalation phase) will be a single ascending, sequential cross-over design in cohorts 1, 2 and 3 of subjects. Cohort 1 and 2 will be 4-way cross-over which includes 4 dosing regimens of GSK3186899 and placebo (3:1 ratio) under fasted conditions. Cohort 3 will be 2-way cross-over which includes 2 treatment periods, 2 dosing regimens in fasted and fed conditions. In Part B (repeat dose escalation phase) subjects will be randomized to receive repeat doses of either GSK3186899 or placebo (3:1 ratio) in either fed or fasted conditions. Part B will be conducted based on the review of all safety, tolerability and PK data from Part A. The study duration includes screening, treatment periods and follow-up.
Interventions
DRUGGSK3186899
GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.
DRUGPlacebo
Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double-blind study. Subjects and Investigator will be blinded to the study treatment.
Intervention model description
Subjects will receive escalating doses of GSK3186899 and placebo in Part A of the study. Subjects will receive repeat doses either of GSK3186899 or placebo in Part B of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the normal reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m\^2) (inclusive). * Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP). * Capable of giving signed informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Up to Week 12 | 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. |
| Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs | Up to Week 9 | 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. |
| Part B: Number of Participants With Non-SAEs and SAEs | Up to Week 9 | 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. |
| 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 | Up to Week 12 | 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(%). |
| Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline | Up to Week 9 | Blood samples were planned to be collected to analyze hematology parameters. |
| Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline | Up to Week 9 | Blood samples were planned to be collected to analyze hematology parameters. |
| Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to Week 12 | 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%. |
| Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to Week 9 | Blood samples were planned to be collected to analyze chemistry parameters. |
| Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to Week 9 | Blood samples were planned to be collected to analyze chemistry parameters. |
| 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 | Up to Week 12 | 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. |
| Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Up to Week 9 | Urine samples were planned to be collected to analyze urine parameters. |
| Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Up to Week 9 | Urine samples were planned to be collected to analyze urine parameters. |
| Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Up to Week 12 | 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. |
| Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings | Up to Week 9 | Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals. |
| Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings | Up to Week 9 | Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals. |
| Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Up to Week 12 | 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%. |
| Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Up to Week 9 | Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest. |
| Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Up to Week 9 | Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest. |
| Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Up to 24 hours post-dose | 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. |
| Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings | Up to 24 hours post-dose | Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest. |
| Part B: Number of Participants Abnormal Cardiac Telemetry Findings | Up to 24 hours post-dose | Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3186899. PK Population consisted of all participants in the Safety Population who received at least 1 non-missing PK assessment. |
| Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3186899. Predicted accumulation ratio is calculated as 1/(1-e\^\[k\*tau\]) where k is elimination rate constant following the single dose and tau is the dosing interval for the intended repeat dosing. |
| Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: Cmax After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: Tmax After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part B: T1/2 After Repeat Dose Administration of GSK3186899 | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899. |
| Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity) | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented. |
| Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity) | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis. |
| Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented. |
| Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax | Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period | Blood samples were planned to be collected at indicated time points for PK analysis. |
| Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau) | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis. |
| Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis. |
| Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose | Blood samples were planned to be collected at indicated time points for PK analysis. |
| Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau) | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose | Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of AUC(0-tau) at Day 10 to AUC(0-tau) at Day 1. |
| Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose | Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Cmax at Day 10 to Cmax at Day 1. |
| Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose | Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Ctau at Day 10 to Ctau at Day 1. |
| Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC | Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose | Blood samples were planned to be collected at indicated time points for PK analysis. Time-invariance ratio was planned to be calculated as AUC(0-12) on Day 10 to AUC(0-infinity) on Day 1. |
Countries
United Kingdom
Participant flow
Recruitment details
This was 2-part study. Part A comprised of 3 Cohorts (Cohorts 1, 2 and 3); Part B comprised 3 cohorts (Cohorts 4, 5 and 6). Study was terminated after completion of Cohort 2, Period 3 of Part A following strategic review after emergence of nonclinical data with non-GlaxoSmithKline asset. Hence, no participants were enrolled in Cohort 2 Period 4 and Cohort 3 of Part A and in all Cohorts of Part B.
Pre-assignment details
A total 25 participants were enrolled (Enrolled Population consisted of all participants who passed screening and entered the study) in this study (Part A: Cohort 1- 11 participants, Cohort 2- 14 participants). Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohort 1-GSK3186899 30 mg/60 mg/120 mg/Placebo Participants in Part A Cohort 1 received a single dose of GSK3186899 30 milligram (mg) on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period. | 3 |
| Part A:Cohort 1-GSK3186899 30 mg/60 mg/Placebo/300 mg Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period. | 2 |
| Part A:Cohort 1-GSK3186899 30 mg/Placebo/120 mg/300 mg Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period. | 2 |
| Part A:Cohort 1-Placebo/GSK3186899 60 mg/120 mg/300 mg Participants in Part A Cohort 1 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period. | 4 |
| Part A:Cohort 2-GSK3186899 300 mg/600 mg/800 mg/Placebo Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period. | 4 |
| Part A:Cohort 2-GSK3186899 300 mg/600 mg/Placebo/Dose Level 7 Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period. | 3 |
| Part A:Cohort 2-GSK3186899 300 mg/Placebo/800 mg/Dose Level 7 Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period. | 3 |
| Part A:Cohort 2-Placebo/GSK3186899 600 mg/800 mg/Dose Level 7 Participants in Part A Cohort 2 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period. | 3 |
| Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed) Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period. | 0 |
| Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted) Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period. | 0 |
| Part B: Cohort 4- GSK3186899 or Placebo Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10. | 0 |
| Part B: Cohort 5- GSK3186899 or Placebo Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10. | 0 |
| Part B: Cohort 6- GSK3186899 or Placebo Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10. | 0 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A: Cohort 1-Period 1 (Day1) | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 1-Period 2 (Day1) | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 1-Period 3 (Day1) | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 2-Period 1 (Day1) | Physician Decision | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 2-Period 1 (Day1) | Randomized in error | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 2-Period 1 (Day1) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 2-Period 2 (Day1) | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort 2-Period 2 (Day1) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A:Cohort 2-GSK3186899 300 mg/600 mg/Placebo/Dose Level 7 | Part A:Cohort 2-GSK3186899 300 mg/Placebo/800 mg/Dose Level 7 | Part A:Cohort 2-Placebo/GSK3186899 600 mg/800 mg/Dose Level 7 | Total | Part A: Cohort 1-GSK3186899 30 mg/60 mg/120 mg/Placebo | Part A:Cohort 1-GSK3186899 30 mg/60 mg/Placebo/300 mg | Part A:Cohort 1-GSK3186899 30 mg/Placebo/120 mg/300 mg | Part A:Cohort 1-Placebo/GSK3186899 60 mg/120 mg/300 mg | Part A:Cohort 2-GSK3186899 300 mg/600 mg/800 mg/Placebo | Part B: Cohort 6- GSK3186899 or Placebo | Part B: Cohort 5- GSK3186899 or Placebo | Part B: Cohort 4- GSK3186899 or Placebo | Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted) | Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 37.3 Years STANDARD_DEVIATION 4.04 | 39.7 Years STANDARD_DEVIATION 8.5 | 41.0 Years STANDARD_DEVIATION 10.54 | 36.9 Years STANDARD_DEVIATION 8.76 | 44.7 Years STANDARD_DEVIATION 6.51 | 34.0 Years STANDARD_DEVIATION 1.41 | 33.0 Years STANDARD_DEVIATION 8.49 | 31.3 Years STANDARD_DEVIATION 8.77 | 34.5 Years STANDARD_DEVIATION 13.2 | — | — | — | — | — |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 3 Participants | 2 Participants | 2 Participants | 19 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 24 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 5 / 14 | 1 / 6 | 2 / 6 | 3 / 6 | 5 / 12 | 2 / 6 | 3 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 3 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 3 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 1 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 1 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 4 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 2 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - clinically significant | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings | Abnormal - not clinically significant | 1 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 5 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 1 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 2 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 3 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 5 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 2 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | Non-SAEs | 3 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs | SAEs | 0 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | 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 | Ketones | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Protein | 2 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Occult blood | 1 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Protein | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Occult blood | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Ketones | 1 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Ketones | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Occult blood | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Protein | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Protein | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Occult blood | 1 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Ketones | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Protein | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Occult blood | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Ketones | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Occult blood | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Ketones | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Protein | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Ketones | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Protein | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Occult blood | 1 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 13 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 11 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 13 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 3 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 13 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 4 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 1 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 1 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 1 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 5 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 4 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 5 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 2 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 4 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 2 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 11 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 11 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 10 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 1 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To low | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Magnesium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To within range or NC | 5 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Potassium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alanine aminotransferase: To high | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Creatinine: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Sodium: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Direct bilirubin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Calcium: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Alkaline phosphatase: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Bilirubin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To high | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | C-reactive protein: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Albumin: To within range or NC | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Phosphate: To within range or NC | 5 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Aspartate aminotransferase: To within range or NC | 5 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline | Protein: To high | 0 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | 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 | WBC count: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Neutrophils: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Basophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Basophils: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Basophils: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Platelets: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | WBC count: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC volume: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hemoglobin: To within range or no change | 13 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hematocrit: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | RBC count: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Eosinophils: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC Hb: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC volume: To within range or no change | 13 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hemoglobin: To high | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Neutrophils: To high | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Platelets: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | RBC count: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | MC volume: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Lymphocytes: To low | 2 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | RBC count: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Neutrophils: To low | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Monocytes: To within range or no change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | WBC count: To high | 1 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Lymphocytes: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- Placebo | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Lymphocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | WBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Platelets: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Eosinophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hematocrit: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Monocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC Hb: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | RBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Basophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Neutrophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Neutrophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hemoglobin: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Basophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Platelets: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC volume: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | MC volume: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Neutrophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Neutrophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Platelets: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Platelets: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC Hb: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hematocrit: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hemoglobin: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC volume: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Basophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | MC volume: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Lymphocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Eosinophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | WBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Monocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | RBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | 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 | Basophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | RBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Basophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Basophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hematocrit: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hemoglobin: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Lymphocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Monocytes: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Neutrophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Neutrophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Platelets: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Platelets: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | WBC count: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC volume: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC volume: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC Hb: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Eosinophils: To within range or no change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Neutrophils: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Monocytes: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | RBC count: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Basophils: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Lymphocytes: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | WBC count: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Eosinophils: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC volume: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hemoglobin: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC volume: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hematocrit: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC Hb: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Basophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Platelets: To low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Platelets: To within range or no change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | 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 | Neutrophils: To within range or no change | 12 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC volume: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Basophils: To high | 1 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hematocrit: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Eosinophils: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Monocytes: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Neutrophils: To low | 1 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC volume: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | RBC count: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Basophils: To within range or no change | 5 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | MC Hb: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hemoglobin: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | WBC count: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Neutrophils: To within range or no change | 5 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Platelets: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Lymphocytes: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Platelets: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Eosinophils: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC Hb: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | WBC count: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Lymphocytes: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC Hb: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Basophils: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | WBC count: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hemoglobin: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC volume: To low | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hemoglobin: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Eosinophils: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Neutrophils: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC volume: To within range or no change | 5 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hemoglobin: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Basophils: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Platelets: To within range or no change | 5 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC volume: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hematocrit: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Eosinophils: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hematocrit: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Platelets: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | MC Hb: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Monocytes: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Basophils: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | RBC count: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Platelets: To low | 1 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Monocytes: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Hematocrit: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Neutrophils: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | RBC count: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Monocytes: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Neutrophils: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | RBC count: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Lymphocytes: To high | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | WBC count: To low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Lymphocytes: To within range or no change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | 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 | Eosinophils: To high | 0 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 2 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 1 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 1 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 2 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 4 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 2 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 3 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
Primary
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
Population: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 14 Participants |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 1 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 5 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 6 Participants |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 12 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 12 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To within Range or No Change | 6 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | SBP: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Respiratory rate: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Body temperature: To High | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | DBP: To Low | 0 Participants |
| Part A: Cohort 2- GSK3186899 800 mg | Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline | Pulse rate: To within Range or No Change | 6 Participants |
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
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
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Time frame: Up to Week 9
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Time frame: Up to Week 9
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Time frame: Up to Week 9
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Primary
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Time frame: Up to Week 9
Population: Safety Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were planned to be collected at indicated time points for PK analysis.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Secondary
Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 1.982 Hour |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 2.955 Hour |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 2.758 Hour |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 3.302 Hour |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 4.655 Hour |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899 | 5.135 Hour |
Secondary
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 739.13 Hours*nanogram per milliliter | Geometric Coefficient of Variation 42.31 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 1607.27 Hours*nanogram per milliliter | Geometric Coefficient of Variation 32.1 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 5287.60 Hours*nanogram per milliliter | Geometric Coefficient of Variation 31.2 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 18265.32 Hours*nanogram per milliliter | Geometric Coefficient of Variation 47.5 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 61539.43 Hours*nanogram per milliliter | Geometric Coefficient of Variation 35.59 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899 | 83867.58 Hours*nanogram per milliliter | Geometric Coefficient of Variation 42.98 |
Secondary
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 725.40 Hours*nanogram per milliliter | Geometric Coefficient of Variation 41.62 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 1597.85 Hours*nanogram per milliliter | Geometric Coefficient of Variation 32.3 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 5268.31 Hours*nanogram per milliliter | Geometric Coefficient of Variation 31.32 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 18105.45 Hours*nanogram per milliliter | Geometric Coefficient of Variation 47.08 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 58201.67 Hours*nanogram per milliliter | Geometric Coefficient of Variation 29.14 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899 | 77531.24 Hours*nanogram per milliliter | Geometric Coefficient of Variation 34.57 |
Secondary
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity) | 1.47 Slope of log dose |
Secondary
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax | 1.19 Slope of log dose |
Secondary
Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 239.206 Nanogram per milliliter | Geometric Coefficient of Variation 34.38 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 356.232 Nanogram per milliliter | Geometric Coefficient of Variation 19.32 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 1214.000 Nanogram per milliliter | Geometric Coefficient of Variation 29.72 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 3011.334 Nanogram per milliliter | Geometric Coefficient of Variation 37.57 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 8219.997 Nanogram per milliliter | Geometric Coefficient of Variation 15.5 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899 | 9445.301 Nanogram per milliliter | Geometric Coefficient of Variation 28.78 |
Secondary
Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3186899. PK Population consisted of all participants in the Safety Population who received at least 1 non-missing PK assessment.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol.Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 246.298 Nanogram per milliliter | Standard Deviation 89.097 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 143.448 Nanogram per milliliter | Standard Deviation 69.7562 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 19.023 Nanogram per milliliter | Standard Deviation 12.41 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 193.372 Nanogram per milliliter | Standard Deviation 75.7409 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 169.883 Nanogram per milliliter | Standard Deviation 79.6579 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 9.447 Nanogram per milliliter | Standard Deviation 6.779 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 182.825 Nanogram per milliliter | Standard Deviation 69.0839 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 71.845 Nanogram per milliliter | Standard Deviation 41.2573 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 124.742 Nanogram per milliliter | Standard Deviation 67.6108 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 48.675 Nanogram per milliliter | Standard Deviation 29.1569 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 33.648 Nanogram per milliliter | Standard Deviation 18.7418 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 36.935 Nanogram per milliliter | Standard Deviation 43.8179 |
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 4.975 Nanogram per milliliter | Standard Deviation 3.8146 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 292.106 Nanogram per milliliter | Standard Deviation 70.6847 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 10.780 Nanogram per milliliter | Standard Deviation 7.4009 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 220.846 Nanogram per milliliter | Standard Deviation 78.82 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 109.636 Nanogram per milliliter | Standard Deviation 61.8823 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 211.540 Nanogram per milliliter | Standard Deviation 98.3222 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 296.102 Nanogram per milliliter | Standard Deviation 44.6567 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 58.322 Nanogram per milliliter | Standard Deviation 30.3314 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 266.122 Nanogram per milliliter | Standard Deviation 76.2478 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 30.156 Nanogram per milliliter | Standard Deviation 14.0233 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 297.366 Nanogram per milliliter | Standard Deviation 98.0691 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 14.662 Nanogram per milliliter | Standard Deviation 9.4905 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 1.526 Nanogram per milliliter | Standard Deviation 1.0015 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 149.386 Nanogram per milliliter | Standard Deviation 77.3929 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 308.820 Nanogram per milliliter | Standard Deviation 76.3337 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 318.288 Nanogram per milliliter | Standard Deviation 101.984 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 1217.430 Nanogram per milliliter | Standard Deviation 414.4935 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 53.978 Nanogram per milliliter | Standard Deviation 33.6205 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 981.000 Nanogram per milliliter | Standard Deviation 287.9601 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 586.375 Nanogram per milliliter | Standard Deviation 187.1841 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 407.900 Nanogram per milliliter | Standard Deviation 132.1951 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 68.788 Nanogram per milliliter | Standard Deviation 50.1741 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 1019.690 Nanogram per milliliter | Standard Deviation 317.4601 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 841.170 Nanogram per milliliter | Standard Deviation 203.0633 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 4.078 Nanogram per milliliter | Standard Deviation 1.2666 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 111.350 Nanogram per milliliter | Standard Deviation 40.8868 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 817.218 Nanogram per milliliter | Standard Deviation 528.0808 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 180.300 Nanogram per milliliter | Standard Deviation 67.3578 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 1165.735 Nanogram per milliliter | Standard Deviation 405.0558 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 2202.511 Nanogram per milliliter | Standard Deviation 908.6908 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 1715.797 Nanogram per milliliter | Standard Deviation 818.4628 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 1413.953 Nanogram per milliliter | Standard Deviation 714.4323 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 1008.525 Nanogram per milliliter | Standard Deviation 554.8121 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 673.839 Nanogram per milliliter | Standard Deviation 419.1869 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 394.246 Nanogram per milliliter | Standard Deviation 259.4013 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 39.462 Nanogram per milliliter | Standard Deviation 31.0353 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 183.693 Nanogram per milliliter | Standard Deviation 151.2143 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 2112.646 Nanogram per milliliter | Standard Deviation 943.7797 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 2445.121 Nanogram per milliliter | Standard Deviation 846.7178 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 2809.873 Nanogram per milliliter | Standard Deviation 731.2502 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 2740.957 Nanogram per milliliter | Standard Deviation 919.9618 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 2661.372 Nanogram per milliliter | Standard Deviation 869.2819 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 2496.468 Nanogram per milliliter | Standard Deviation 751.3136 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 457.593 Nanogram per milliliter | Standard Deviation 549.4177 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 6388.922 Nanogram per milliliter | Standard Deviation 1338.2507 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 5230.308 Nanogram per milliliter | Standard Deviation 1817.4993 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 6676.070 Nanogram per milliliter | Standard Deviation 1731.999 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 3752.580 Nanogram per milliliter | Standard Deviation 662.1178 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 6213.155 Nanogram per milliliter | Standard Deviation 2228.1232 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 7377.713 Nanogram per milliliter | Standard Deviation 1718.2385 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 6930.995 Nanogram per milliliter | Standard Deviation 1697.9608 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 2571.757 Nanogram per milliliter | Standard Deviation 1287.9872 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 1818.825 Nanogram per milliliter | Standard Deviation 952.883 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 528.360 Nanogram per milliliter | Standard Deviation 530.7085 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 3196.830 Nanogram per milliliter | Standard Deviation 1133.3168 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 3910.825 Nanogram per milliliter | Standard Deviation 1174.7813 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 5337.077 Nanogram per milliliter | Standard Deviation 1679.9417 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 30 minutes | 7563.453 Nanogram per milliliter | Standard Deviation 3748.7402 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 24 hours | 787.852 Nanogram per milliliter | Standard Deviation 862.1917 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 4 hours | 6492.033 Nanogram per milliliter | Standard Deviation 2264.4485 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1 hour | 8148.812 Nanogram per milliliter | Standard Deviation 3230.826 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 12 hours | 2676.418 Nanogram per milliliter | Standard Deviation 1366.817 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 hours | 3519.375 Nanogram per milliliter | Standard Deviation 1243.8441 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 1.5 hours | 7828.908 Nanogram per milliliter | Standard Deviation 1936.6359 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 8 hours | 4352.842 Nanogram per milliliter | Standard Deviation 1510.7803 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 3 hours | 8306.098 Nanogram per milliliter | Standard Deviation 2966.1881 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2 hours | 8139.085 Nanogram per milliliter | Standard Deviation 1761.2188 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 6 hours | 5010.553 Nanogram per milliliter | Standard Deviation 1424.1685 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 5 hours | 5828.517 Nanogram per milliliter | Standard Deviation 1559.1849 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 2.5 hours | 7714.882 Nanogram per milliliter | Standard Deviation 2565.6688 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | 10 minutes | 766.898 Nanogram per milliliter | Standard Deviation 691.4467 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899 | Pre-dose | 0.000 Nanogram per milliliter | Standard Deviation 0 |
Secondary
Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899. Predicted accumulation ratio is calculated as 1/(1-e\^\[k\*tau\]) where k is elimination rate constant following the single dose and tau is the dosing interval for the intended repeat dosing.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.0183 Ratio | Standard Deviation 0.01324 |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.0631 Ratio | Standard Deviation 0.03952 |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.0704 Ratio | Standard Deviation 0.04505 |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.0889 Ratio | Standard Deviation 0.03246 |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.2603 Ratio | Standard Deviation 0.19948 |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899 | 1.3429 Ratio | Standard Deviation 0.26138 |
Secondary
Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Cohorts 1 and 2- Placebo | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 1.00 Hour |
| Part A: Cohort 1- GSK3186899 30 mg | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 3.00 Hour |
| Part A: Cohort 1- GSK3186899 60 mg | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 1.00 Hour |
| Part A: Cohort 1- GSK3186899 120 mg | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 2.00 Hour |
| Part A: Cohorts 1 and 2- GSK3186899 300 mg | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 2.75 Hour |
| Part A: Cohort 2- GSK3186899 600 mg | Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899 | 2.50 Hour |
Secondary
Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Population: PK Population. Data was not collected for this endpoint as it was incorrectly stated as one of the Secondary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to Ctau for single ascending dose part was an error. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was planned to be presented in a single arm because of similar dosing strategies as pre-defined in the protocol.
Secondary
Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Cmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau
Blood samples were planned to be collected at indicated time points for PK analysis.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of AUC(0-tau) at Day 10 to AUC(0-tau) at Day 1.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Cmax at Day 10 to Cmax at Day 1.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Ctau at Day 10 to Ctau at Day 1.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: T1/2 After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC
Blood samples were planned to be collected at indicated time points for PK analysis. Time-invariance ratio was planned to be calculated as AUC(0-12) on Day 10 to AUC(0-infinity) on Day 1.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.
Secondary
Part B: Tmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Population: PK Population. Data was not collected as no participants were enrolled in Part B.