Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.
Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).
Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP)
Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides
Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Chemistry Parameter: Glucose
Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 1: Number of Participants With Abnormal Urinalysis
Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Signs: Pulse Rate
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Signs: Temperature
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Sign: Respiratory Rate
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
Part 2: Number of Participants AEs and SAEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.
Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Hb
Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP
Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides
Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Glucose
Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Protein
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Number of Participants With Abnormal Urinalysis
Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Part 2: Change From Baseline in Vital Signs: SBP and DBP
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Vital Sign: Pulse Rate
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Vital Sign: Temperature
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Vital Sign: Respiratory Rate
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Number of Participants With Abnormal ECG Findings
12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.
Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Most of the concentrations were below limit of quantification (BLQ) at this dose group this value and/ or %AUC extrapolated was >20% for all participants so this value should be used with caution. Results are presented treatment wise.
Part 1: Apparent Oral Clearance (CL/F) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: AUC(0-24) of GSK3640254: Day 1
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: Cmax, C24 of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: Tmax, Tlag of GSK3640254 on Day 1
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Part 2: Tmax GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: Cmax of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The PK parameter name for Part 2 (Day 14) trough concentration was changed using Phoenix WinNonlin 8 from Ct to Ctrough. Day 15 Ctrough values were used for dose proportionality and time to steady-state assessments.
Part 2: T1/2 of GSK3640254: Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Part 2: CL/F of GSK3640254: Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 15 and Day 2, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. results are presented treatment wise.
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.