GSK3858279

An AE is defined as 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. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169.

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of change from baseline in hematology parameters Hemoglobin. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of change from baseline in hematology parameters Hematocrit. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of hematology parameters including (WBC) count with differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of clinical chemistry parameters including total Protein. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of clinical chemistry parameters including Total bilirubin. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of clinical chemistry parameters including Direct bilirubin, Creatinine. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Blood samples were collected for the assessment of clinical chemistry parameters including Urea, Glucose, Potassium, Sodium. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline 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, indicated as ratio of urine density to water density. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline 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. 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). The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.

The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as increase to trace, increase to 1+ (low concentrations present), increase to 2+ (moderate concentrations present) and increase to 3+ (high concentrations present) indicating proportional concentrations in the urine sample. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for worst-case post-Baseline relative to Baseline is presented.

The vital sign followed in this analysis was both systolic and diastolic blood pressure, expressed as millimetre of mercury. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

The vital signs followed in this analysis was pulse rate, expressed as beats per minute. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

The vital sign followed in this analysis was body temperature, expressed as degree Celsius. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

The vital signs followed in this analysis was respiratory rate, expressed as Breaths per minute. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Change from Baseline was defined as value at the indicated time point minus Baseline value.

Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. The final follow-up visit was on Day 169 for participants in the Caucasian cohort and on Day 113 for Chinese and Japanese participants respectively (NB: Japanese and Chinese participants had an option to remain in the study until Day 169). Baseline was defined as the average of the triplicate pre-dose assessments on Day 1 of Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

An Adverse Event (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. TEAE is defined as an AE that occurred on or after the first dose date of study intervention. SAEs is defined as any serious adverse event that, at any dose which 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, other situations as per investigator's medical or scientific judgment.

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. TEAE is defined as an AE that occurred on or after the first dose date of study intervention. SAEs is defined as any serious adverse event that, at any dose which 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, other situations as per investigator's medical or scientific judgment.

The parameters evaluated for Hematology were Basophils, Eosinophils, Hematocrit, Hemoglobin (Hg), Lymphocytes, mean corpuscular Hg, mean corpuscular volume, Monocytes, Platelet count, Red blood cells, Reticulocytes, Total Neutrophils, White blood cells count (WBC). For Clinical Chemistry- Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium, Creatinine, Direct bilirubin, Glucose, Potassium, Sodium, Total bilirubin, Total protein, TroponinT, N-terminal pro B-type natriuretic peptide (NT-ProBNP) and Urea. For Urinalysis-Urine bilirubin, Occult blood, Glucose, Ketones, Nitrates, pH, Protein, Specific gravity, Urobilinogen and Leukocyte Esterase for detecting WBC. Changes from baseline in hematology, clinical chemistry and urinalysis were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

The parameters evaluated for Hematology were Basophils, Eosinophils, Hematocrit, Hemoglobin (Hg), Lymphocytes, mean corpuscular Hg, mean corpuscular volume, Monocytes, Platelet count, Red blood cells, Reticulocytes, Total Neutrophils, White blood cells count (WBC). For Clinical Chemistry- Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium, Creatinine, Direct bilirubin, Glucose, Potassium, Sodium, Total bilirubin, Total protein, TroponinT, N-terminal pro B-type natriuretic peptide (NT-ProBNP) and Urea. For Urinalysis-Urine bilirubin, Occult blood, Glucose, Ketones, Nitrates, pH, Protein, Specific gravity, Urobilinogen and Leukocyte Esterase for detecting WBC. Changes from baseline in hematology, clinical chemistry and urinalysis were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

Twelve-lead Electrocardiogram (ECG) were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, Uncorrected QT and corrected QT intervals (QTc) intervals. Changes from baseline in ECG findings were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

Twelve-lead Electrocardiogram (ECG) were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, Uncorrected QT and corrected QT intervals (QTc) intervals. Changes from baseline in ECG findings were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Changes from baseline in vital signs were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Changes from baseline in vital signs were reviewed by the investigator, medical monitor and safety physician to determine clinical significance; the number of participants with clinically significant changes is reported.

Change from Baseline in knee pain due to Osteoarthritis were reported by average of daily pain numeric rating scale (NRS) at Week 8. The pain NRS is an 11-point scale (ranging from 0-10) for self-reporting of average knee pain where 0 indicates no pain, and 10 indicates the worst possible pain. For each participant, the mean pain score prior to each visit was calculated as the average pain intensity in the 7 days prior to assessment visit. Participants were instructed to complete the pain NRS questionnaire at approximately the same time each day. A negative value change from baseline indicates an improvement. Baseline scores for each participant were assigned based on the first dosing visit.

Change from Baseline in worst knee pain intensity were assessed using NRS at Week 8. The pain NRS is an 11-point scale (ranging from 0-10) for self-reporting of average knee pain where 0 indicated no pain, and 10 indicated worst possible pain. The mean pain score prior to each visit was calculated as the average pain intensity in the 7 days prior to assessment visit. Participants were instructed to complete the pain NRS questionnaire at approximately the same time each day. A negative value change from baseline indicates an improvement. Baseline scores for each participant were assigned based on the first dosing visit.