Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants

Number of Participants With Adverse Events (AEs)

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.

Time frame: From Day 1 (first dose) up to 14 days post last dose in each treatment period

Number of Participants With Serious Adverse Events (SAEs)

A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Time frame: From the signing of the informed consent form (a period starting up to 28 days before the first dose on Day 1) to up to 14 days after the last dose of each treatment period

Number of Participants With Treatment Emergent AEs (TEAEs) and Treatment Emergent SAEs

A TEAE and treatment emergent SAE is considered any untoward medical occurrence in a clinical study participant, considered by the investigator to have a causal relationship with study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Time frame: From Day 1 (first dose) up to 2 days post last dose in each treatment period

Summary of Change From Baseline in Hematology Parameters: Basophils, Neutrophils, Eosinophils, Lymphocytes, Monocytes and Platelets

Blood samples were collected for the assessment of the hematology parameters: basophils, neutrophils, eosinophils, lymphocytes, monocytes and platelets. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. Standard deviation (SD)=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Volume

Blood samples were collected for the assessment of the hematology parameters: mean corpuscular volume. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin

Blood samples were collected for the assessment of the hematology parameters: mean corpuscular hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Hematology Parameters: Erythrocytes and Reticulocytes

Blood samples were collected for the assessment of the hematology parameters: erythrocytes and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Hematology Parameters: Hemoglobin

Blood samples were collected for the assessment of the hematology parameters: hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Hematology Parameters: Hematocrit and Reticulocytes

Blood samples were collected for the assessment of the hematology parameters: hematocrit and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT)

Blood samples were collected for the assessment of the clinical chemistry parameters: ALT, ALP, AST, CPK, and GGT. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: Albumin, Protein

Blood samples were collected for the assessment of the clinical chemistry parameters: albumin and protein. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Calcium Corrected for Albumin, Glucose, Lactic Acid, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, and Urea

Blood samples were collected for clinical chemistry parameters: bicarbonate, calcium corrected for albumin, glucose, lactic acid, magnesium, phosphate, potassium, sodium, triglycerides, urea. Baseline was defined as the last non-missing pre-dose assessment for each cohort. Generally, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments on Day 1 lacked timing, the first recorded was used. If one Day 1 assessment lacked timing, the last available from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, Baseline was set to missing. Change from baseline is defined as post-dose value minus baseline value. SD=0.0000 indicates SD below the detectable assay limit, approximated to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin

Blood samples were collected for the assessment of the clinical chemistry parameters: bilirubin, creatinine, direct bilirubin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: C-reactive Protein (CRP)

Blood samples were collected for the assessment of the clinical chemistry parameters: CRP. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Clinical Chemistry Parameters: pH

Blood samples were collected for the assessment of the clinical chemistry parameters: pH. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Number of Participants With Worst-case Urinalysis Results

Urine samples were collected for the assessment of urinalysis parameters, which include pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

Time frame: From Day 1 up to 14 Days post last dose

Summary of Change From Baseline in Physical Examinations: Body Mass Index (BMI)

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Vital Signs: Respiratory Rate

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of Change From Baseline in Vital Signs: Supine Diastolic Blood Pressure, Supine Systolic Blood Pressure

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of Change From Baseline in Vital Signs: Supine Pulse Rate

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of Change From Baseline in Vital Signs: Tympanic Membrane Temperature

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of Change From Baseline in Physical Examinations: Weight

Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.

Time frame: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of Change From Baseline in ECG Parameters: PR Interval, QRS Interval, QT Interval, Corrected QT (QTc) Interval, QT Interval Corrected Using Bazett's Formula, QT Interval Corrected, Using Fridericia's Formula

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically measured the PR interval, QRS interval, QT interval, and QTc interval. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.

Time frame: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Number of Participants With Abnormal Cardiac Telemetry Findings

Telemetry is defined as the continuous monitoring of a participant's heart rate and rhythm from a remote location.

Time frame: Up to 24 hours post first dose on Day 1