Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK3640254 · 10 trials · 2 indications
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was 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.
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was 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.
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.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. Area under the plasma concentration-time curve from time zero to time t, to be calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods
Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.
Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.
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.
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.
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.
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.
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.
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. .
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.
Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as AUC(0-inf) is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as T1/2 is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative amount \[Ae\]\[Urine\] for Period 1)/(Plasma AUC\[0-inf\]).
Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative Ae\[Urine\] for Period 2)/(Plasma AUC\[0-inf\]).
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.
Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(Oral Tablet)/Dose(Oral Tablet) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses were analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters.
Blood samples were collected at the indicated time points for PK analysis. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).
Blood samples were collected at the indicated time points for PK analysis. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100.
Blood samples were collected at the indicated time points for PK analysis. Fg is defined as the fraction metabolized by gut wall as a fraction of the oral dose and was expressed as 1 minus Metabolite load following intravenous and oral administration multiplied by 100.
Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. Not applicable (NA) indicates that No concentration values detected for pre-dose.
Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.
Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. NA indicates that No concentration values detected for pre-dose.
Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis. The PK population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic Parameter Population consisted of all participants who underwent plasma pharmacokinetic sampling and had evaluable pharmacokinetic parameters estimated.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.
Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.
| Arm | Type | Description |
|---|---|---|
| Part 1: GSK3640254 10 mg | EXPERIMENTAL | Participants will receive GSK3640254 10 milligram (mg), capsules, orally for 10 days. |
| Part 1: GSK3640254 200 mg | EXPERIMENTAL | Participants will receive GSK3640254 200 mg, capsules, orally for 10 days. |
| Part 1: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo capsules, orally for 10 days. |
| Part 2: GSK3640254 40 mg | EXPERIMENTAL | Participants will receive GSK3640254 40 mg, capsules, orally for 7 days. |
| Part 2: GSK3640254 80 mg | EXPERIMENTAL | Participants will receive GSK3640254 80 mg, capsules, orally for 7 days. |
| Part 2: GSK3640254 140 mg | EXPERIMENTAL | Participants will receive GSK3640254 140 mg, capsules, orally for 7 days. |
| Part 2: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo capsules, orally for 7 days. |
| Part 1 : Treatment sequence ABC | EXPERIMENTAL | Participants will receive a single oral dose of GSK3640254 25 milligrams (mg) (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 1, followed by a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 2. In Period 3, participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C). |
| Part 1 : Treatment sequence BCA | EXPERIMENTAL | Participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 1, followed by a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A). |
| Part 1 : Treatment sequence CAB | EXPERIMENTAL | Participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in period 1, followed by a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B). |
| Part 2 : Treatment sequence DE | EXPERIMENTAL | Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 2. |
| Part 2 : Treatment sequence ED | EXPERIMENTAL | Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 2. |
| Probe Substrates/GSK3640254 200 mg/Probe Substrates+GSK3640254 | EXPERIMENTAL | All participants will receive a single dose of treatment A: Probe substrates (caffeine 200 milligram \[mg\], metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1; followed by treatment B- GSK3640254 200 mg on Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21. |
| Part 1: Participants receiving placebo | PLACEBO_COMPARATOR | Participants will receive a single dose of placebo once daily for 7 days following ingestion of a moderate fat meal. |
| Part 1: Participants receiving GSK3640254 500 milligrams (mg) | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 500 mg once daily for 7 days following ingestion of a moderate fat meal. |
| Part 2: Main QTc Study | EXPERIMENTAL | Participants will be randomized to 1:1:1:1 ratio to receive Treatment T- Therapeutic dose of GSK3640254 (100 mg QD) on Days 1 through 7 or Treatment ST- Supratherapeutic dose of GSK3640254 (to be determined from Part 1) on Days 1 through 7 or Treatment P- Placebo for GSK3640254 on Days 1 through 7 or Treatment M- Moxifloxacin (GSK3640254 placebo Days 1 through 6 and a single dose of Moxifloxacin \[400 mg\] on Day 7 in 4 treatment periods. There will be at least 7 days wash out period between each period. |
| Cohort 1: GSK3640254 then DRV/RTV then GSK3640254 + DRV/RTV | EXPERIMENTAL | Cohort 1 will include 3 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 DRV/RTV will be administered (Treatment B). In Period 3 GSK3640254 (Treatment A) and DRV/RTV (Treatment B) will be administered. |
| Cohort 2: GSK3640254 then ETR then GSK3640254 + ETR | EXPERIMENTAL | Cohort 2 will include 3 periods. In Period 1 GSK3640254 will be given (Treatment A). In Period 2 ETR will be given (Treatment C). In Period 3 GSK3640254 (Treatment A) and ETR (Treatment C) will be administered. |
| Cohort 3: GSK3640254 then GSK3640254 + DRV/RTV + ETR | EXPERIMENTAL | Cohort 3 will include 2 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 GSK3640254 (Treatment A), DRV/RTV (Treatment B), and ETR (Treatment C) will be administered. |
| GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension | EXPERIMENTAL | Participants will receive a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal. Participants will then be administered a 100 microgram (mcg) dose (approximately 3.7 kilobecquerel; 100 nano Curie) of \[14C\]-GSK3640254 as an IV infusion for 1 hour on Day 1 in treatment Period 1, On Day 1 in treatment Period 2, participants will receive a single oral dose of 85 mg (approximately 3.15 megabecquerel; 85 micro Curie) \[14C\]-GSK3640254 administered as an oral suspension with a moderate fat meal. A wash out period of at least 13 days will be maintained between oral doses of treatment periods. |
| Part 1: Treatment AB | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 1: Treatment BA | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment CDE | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment DEC | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment ECD | EXPERIMENTAL | Participants will receive a single dose of GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Portia followed by Portia co-administered with GSK3640254 | EXPERIMENTAL | Subjects will be administered Portia (0.03 mg EE/0.15 mg LNG) once daily on Days -3 to -1 during run-in period and on Days 1 to 10 in treatment period A. Subjects will then receive Portia (0.03 mg EE/0.15 mg LNG) co-administered with GSK3640254 200 mg once daily on Days 11 to 21 in treatment period B. |
| DTG followed by GSK3640254 followed by DTG+GSK3640254 | EXPERIMENTAL | Subjects will receive DTG 50 mg QD on Days 1 through 5 in Period 1 followed by a wash-out period of 4 days. Subjects will then receive GSK3640254 200 mg QD on Days 1 through 7 in Period 2 followed by co-administration of DTG 50 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Period 3. |
| Subjects in cohort 1-2: Part 1 | EXPERIMENTAL | Eligible subjects will participate in cohort 1 or 2 and each of these two cohorts will contain up to four escalating doses of GSK3640254. In each cohort, 6 subjects will be randomized to receive single oral dose of GSK3640254 and 2 subjects will be randomized to receive placebo. Hence, each subject in cohort 1 and 2 will receive up to 3 escalating doses of GSK3640254 and one placebo in crossover manner. |
| GSK3640254 receivers (cohort 3-6 and expansion): Part 2 | EXPERIMENTAL | Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 6 subjects will be randomized to receive a once-daily oral dose of GSK3640254 for 14 days. After the safety data of cohort 3-6 is available, 18 eligible subjects will be randomized to receive once daily oral dose of GSK3640254 for 14 days in expansion cohort. |
| Subjects receiving placebo (cohort 3-6): Part 2 | PLACEBO_COMPARATOR | Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 2 subjects will be randomized to receive a once-daily oral dose of placebo for 14 days. After the safety data of cohort 3-6 is available, 6 eligible subjects will be randomized to receive once daily oral dose of placebo for 14 days in expansion cohort. |
| Name | Type | Description |
|---|---|---|
| GSK3640254 | DRUG | GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water. |
| Placebo matching GSK3640254 Mesylate salt | DRUG | Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water |
| DTG | DRUG | DTG will be administered via oral route. |
| GSK3640254/DTG | DRUG | GSK3640254/DTG will be administered via oral route. |
| GSK3640254 200 mg | DRUG | GSK3640254 will be available as oral tablets at unit dose strength of 100 mg. |
| Caffeine 200 mg | DRUG | Caffeine will be available as oral tablets at unit dose strength of 200 mg. |
| Metoprolol 100 mg | DRUG | Metoprolol will be available as oral tablets at unit dose strength of 100 mg. |
| Montelukast 10 mg | DRUG | Montelukast will be available as oral tablets at unit dose strength of 10 mg. |
| Flurbiprofen 100 mg | DRUG | Flurbiprofen will be available as oral tablets at unit dose strength of 100 mg. |
| Omeprazole 40 mg | DRUG | Omeprazole will be available as oral capsules at unit dose strength of 40 mg. |
| Midazolam 5 mg (2.5 mL) | DRUG | Midazolam will be available as syrup for oral administration at unit dose strength of 2 milligram per milliliter (mg/mL). |
| Digoxin 0.25 mg | DRUG | Digoxin will be available as oral tablet at unit dose strength of 0.25 mg. |
| Pravastatin 40 mg | DRUG | Pravastatin will be available as oral tablet at unit dose strength of 40 mg. |
| Placebo | DRUG | Placebo will be administered. |
| Moxifloxacin | DRUG | Moxifloxacin will be administered. |
| Darunavir/Ritonavir (DRV/RTV) | DRUG | DRV/RTV will be available as oral tablets. |
| Etravirine (ETR) | DRUG | ETR will be available as oral tablets. |
| GSK3640254 Oral tablet | DRUG | GSK3640254 will be available as white film-coated round tablets to be administered via oral route with meal in the morning with 240 milliliter (mL) of water at room temperature. |
| [14C]-GSK3640254 intravenous infusion | DRUG | \[14C\]-GSK3640254 will be available as clear, colorless solution free from visible particulates to be administered via the IV route. |
| [14C]-GSK3640254 powder | DRUG | \[14C\]-GSK3640254 will be available as white powder to be reconstituted into a suspension with 25 mL of vehicle before dosing so as to administer 85 mg dose with meal in the morning. |
| GSK3640254 Tablet | DRUG | GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. |
| GSK3640254 Capsule | DRUG | GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. |
| Portia | DRUG | Portia will be available in the form of tablets containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel. |
Inclusion Criteria: * Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent. * Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, labora...
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GSK3640254 is an investigational small molecule being developed for the treatment of HIV infections, including human immunodeficiency virus infection. It is currently in Phase 2 clinical development and has not been approved by regulatory authorities.
GSK3640254 is being developed by GSK plc, a pharmaceutical company listed on the stock exchange under the ticker GSK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in treating HIV infections.
GSK3640254 is currently in Phase 2 clinical development. It is an investigational drug, meaning it has not yet received regulatory approval. The drug has completed nine clinical trials, including Phase 1 studies in healthy volunteers and drug interaction studies.
GSK3640254 has completed nine clinical trials, including NCT03231943, a first-time-in-human study in healthy volunteers, and NCT03816696, a pharmacokinetic interaction study with dolutegravir. Other completed trials include NCT04630002, a drug-drug interaction study with darunavir/ritonavir and etravirine, and NCT04857892, a bioavailability and food-effect study.
No, GSK3640254 is not the same as dolutegravir. GSK3640254 is a separate investigational drug being studied for HIV infections. Clinical trials have evaluated GSK3640254 in combination with dolutegravir, including a fixed-dose combination study, but they are distinct compounds.