A Relative Bioavailability and Food-Effect Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir (DTG) in Healthy Participants

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of DTG.

Blood samples were collected at indicated time points for PK analysis of DTG.

Blood samples were collected at indicated time points for PK analysis of DTG.

Blood samples were collected at indicated time points for PK analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of GSK3640254.

Blood samples were collected at indicated time points for PK analysis of DTG.

Blood samples were collected at indicated time points for PK analysis of DTG.

Blood samples were collected at indicated time points for PK analysis of DTG.

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 serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.

An 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 serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameters: hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: serum lipase and serum amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: serum lipase, serum amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: lipase and amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: lipase and amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Blood samples were collected to analyze the chemistry parameters: Creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Urine samples were collected to analyze the urinalysis parameter: 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 visit, prior to the first study drug administration in each treatment period.

Urine samples were collected to analyze the urinalysis parameter: 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 visit, prior to the first study drug administration in each treatment period.

Urine samples were collected to analyze the urinalysis parameter: pH. 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected to analyze the urinalysis parameter: pH. 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including glucose by dipstick. Urinalysis included dipstick urine test which was used to screen for glucose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including glucose by dipstick. Urinalysis included dipstick urine test which was used to screen for glucose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including protein by dipstick. Urinalysis included dipstick urine test which was used to screen for protein. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine protein can be read as negative, and trace in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including protein by dipstick. Urinalysis included dipstick urine test which was used to screen for protein. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine protein can be read as negative, and trace in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including occult blood by dipstick. Urinalysis included dipstick urine test which was used to screen for occult blood. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including occult blood by dipstick. Urinalysis included dipstick urine test which was used to screen for occult blood. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including ketones by dipstick. Urinalysis included dipstick urine test which was used to screen for ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine ketones can be read as negative, trace, 2+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including ketones by dipstick. Urinalysis included dipstick urine test which was used to screen for ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine ketones can be read as negative, trace, 1+, 2+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including bilirubin and nitrite by dipstick. Urinalysis included dipstick urine test which was used to screen for bilirubin and nitrite. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine bilirubin and nitrite can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including bilirubin and nitrite by dipstick. Urinalysis included dipstick urine test which was used to screen for bilirubin and nitrite. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine bilirubin and nitrite can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including leukocyte esterase by dipstick. Urinalysis included dipstick urine test which was used to screen for leukocyte esterase. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine leukocyte esterase can be read as negative, trace, 1+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected at indicated time points to analyze parameters including leukocyte esterase by dipstick. Urinalysis included dipstick urine test which was used to screen for leukocyte esterase. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine leukocyte esterase can be read as negative, trace indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.

Urine samples were collected to analyze the urinalysis parameter: 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 visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Urine samples were collected to analyze the urinalysis parameter: 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 visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Urine samples were collected to analyze the urinalysis parameter: pH. 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Urine samples were collected to analyze the urinalysis parameter: pH. 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. 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.

Urine samples were collected to analyze the urine parameter: glucose. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Urine samples were collected to analyze the urine parameter: glucose. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Urine samples were collected to analyze the urine parameter: protein. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Urine samples were collected to analyze the urine parameter: protein. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Urine samples were collected to analyze the urine parameter: erythrocytes. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Urine samples were collected to analyze the urine parameter: erythrocytes. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.

Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, and QTcF interval . Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment

Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, and QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment.

Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment.

SBP and DBP were measured in the semi-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 average of the triplicate predose assessments within each treatment.

Pulse rate was measured in the semi-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 average of the triplicate predose assessments within each treatment.

Pulse rate was measured in the semi-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 average of the triplicate predose assessments within each treatment.

Oral temperature were measured in the semi-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 average of the triplicate predose assessments within each treatment.

Oral temperature were measured in the semi-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 average of the triplicate predose assessments within each treatment.

Respiratory rate was measured in the semi-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 average of the triplicate predose assessments within each treatment.

Respiratory rate was measured in the semi-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 average of the triplicate predose assessments within each treatment.

SBP and DBP were measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

SBP and DBP were measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Pulse rate was measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Pulse rate was measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Oral temperature was measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Oral temperature was measured in the semi-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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Respiratory rate was measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Respiratory rate was measured in the semi-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 average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.