A Study to Evaluate the Effect of Therapeutic and Supratherapeutic Oral Doses of GSK3640254 on Cardiac Conduction as Assessed by 12-Lead Electrocardiogram Compared to Placebo and a Single Oral Dose of Moxifloxacin in Healthy Adult Participants

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

时间窗: Up to Day 9

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.

Part 1: Absolute Values for Hematology Parameter: Hemoglobin

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at idicated time points to analyze erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Magnesium, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, and Blood Urea Nitrogen

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze glucose, cholesterol, magnesium, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium, and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods.

Part 1: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

Part 1: Maximum Observed Concentration (Cmax) of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

Part 1: Time of Maximum Observed Concentration (Tmax) of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

Part 1: Plasma Concentration of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.

Part 1: Absolute Values for Hematology Parameter: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. .

Part 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Hematology Parameter: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase, and Lactate Dehydrogenase

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze ALT, ALP, AST, GGT, creatine kinase, and lactate dehydrogenase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Plasma Concentration of Major Metabolites of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.

Part 1: Absolute Values for Hematology Parameter: Hematocrit

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Hematology Parameter: Hematocrit

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated timepoints to analyze hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Absolute Values for Hematology Parameter: Erythrocytes

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Absolute Values for Chemistry Parameters: Creatinine, Urate, Total Bilirubin, and Direct Bilirubin

时间窗: Baseline (Day -2), Day 3, Day 7, Day 9

Blood samples were collected at indicated timepoints to analyze creatinine, urate, total bilirubin, and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Chemistry Parameters: Albumin, Globulin, and Total Protein

时间窗: Baseline (Day -2), Day 3, Day 7, Day 9

Blood samples were collected at indicated timepoints to analyze albumin, globulin, and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Chemistry Parameters: Amylase and Lipase

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated timepoints to analyze amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Magnesium, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze glucose, cholesterol, magnesium, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium, and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, Creatine Kinase, Lactate Dehydrogenase

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated time points to analyze ALT, ALP, AST, GGT, creatine kinase, and lactate dehydrogenase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Urate, Total Bilirubin, Direct Bilirubin

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated timepoints to analyze creatinine, urate, total bilirubin, and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Chemistry Parameters: Albumin, Globulin, and Total Protein

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated timepoints to analyze albumin, globulin, and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value

Part 1: Change From Baseline in Chemistry Parameters: Amylase and Lipase

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Blood samples were collected at indicated timepoints to analyze amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Urine samples were collected at indicated time points to analyze the urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Urinalysis Parameter: Potential of Hydrogen (pH)

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Urine samples were collected at indicated time points to analyze the urine pH by dipstick test. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Urine samples were collected at indicated time points to analyze the urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Change From Baseline in Urinalysis Parameter: pH

时间窗: Baseline (Day -2), Day 3, Day 7, and Day 9

Urine samples were collected at indicated time points to analyze the urine pH by dipstick test. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Part 1: Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings

时间窗: Baseline(Day-2), Day1: 2 Hours, 4 Hours, 6 Hours; Day 4: 2 Hours, 4 Hours, 6 Hours, Day 7: 2 Hours, 4 Hours, 6 Hours and Day 9

A 12-lead ECG was recorded with the participant in a supine position. 12-lead ECGs were obtained by using an automated ECG machine. 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 clinically significant abnormal 12-Lead ECG findings has reported

Part 1: Absolute Values for Vital Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

时间窗: Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

SBP and DBP were measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Vital Parameter: Pulse Rate

时间窗: Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

Pulse rate was measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Absolute Values for Vital Parameter: Temperature

时间窗: Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

Temperature was measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions.Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 2: Placebo-corrected Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Following Administration of GSK3640254 100 mg and GSK3640254 500 mg Using Concentration-QTc (C-QTc) Analysis

时间窗: Baseline (Pre-dose, Day 1) and up to Day 7

Twelve-lead ECGs were recorded in participant using automated ECG machine \& performed with participant in supine position after a rest of at least 10 minutes.Baseline was defined as the latest pre-dose assessment with a non-missing value for each visit. Change from Baseline was calculated by subtracting Baseline value from post dose value. Placebo-corrected change from Baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF) was calculated as difference in model-predicted mean change from Baseline in QTcF between treatment groups using C-QTc analysis. A linear mixed-effects model with change from Baseline in QTcF as the dependent variable, time-matched GSK3640254 plasma concentration as a fixed effect, centered Baseline as additional covariate,treatment \&time as categorical factors, \& a random intercept \& slope per participant. In all calculations, concentrations in participants who received placebo were set to 0.

Part 2: Plasma Concentration of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 8 Hours, 10 Hours, 12 Hours, 24 Hours post-dose on Day 7 in each treatment period

Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.

Part 2: Plasma Concentration of Major Metabolites of GSK3640254

时间窗: Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 8 Hours, 10 Hours, 12 Hours, 24 Hours post-dose on Day 7 in each treatment period

Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.