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Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03836729
Recruitment Status : Completed
First Posted : February 11, 2019
Results First Posted : April 2, 2020
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE February 7, 2019
First Posted Date  ICMJE February 11, 2019
Results First Submitted Date  ICMJE March 17, 2020
Results First Posted Date  ICMJE April 2, 2020
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE February 11, 2019
Actual Primary Completion Date March 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
  • Period 2: AUC (0-tau) of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Maximum Observed Concentration (Cmax) of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Cmax of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: AUC (0-tau) of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: AUC (0-tau) of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 1:Cmax of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2:Cmax of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Ctau of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: AUC (0-tau) of Tenofovir (TFV) [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: AUC (0-tau) of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Cmax of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Cmax of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Ctau of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Ctau of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Area under the plasma concentration-time curve (AUC) from time 0 to the end of the dosing interval at steady state (AUC[0-tau]) for TAF [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TAF.
  • Maximum observed concentration (Cmax) for TAF [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TAF.
  • AUC(0-tau) for FTC [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of FTC.
  • Cmax for FTC [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of FTC.
  • Plasma concentration at the end of the dosing interval (Ctau) for FTC [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of FTC.
  • AUC(0-tau) for Tenofovir (TFV) [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TFV.
  • Cmax for TFV [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TFV.
  • Ctau for TFV [ Time Frame: Days 2 to 13 and Day 14 (0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose) in Period 1; Days 1 to, 2, 3, 4, 5, 6 and Day 7 (0.25, 0.5, 0.75 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TFV.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE) [ Time Frame: Up to Day 24 ]
    An adverse events (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: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before
  • Period 1: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: Baseline and at Days 7, and 14 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated timepoints for analysis for hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: Baseline and at Days 7, and 14 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Hematology Parameter of Hematocrit [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameter like hematocrit. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of Hematocrit [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like hematocrit. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter: Hematocrit [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time points for analysis for hematology parameter like hematocrit. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter: Hematocrit [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like hematocrit. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Hematology Parameter of Hemoglobin [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated timepoints for analysis for hematology parameter like hemoglobin. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of Hemoglobin [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameter like hemoglobin. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter: Hemoglobin [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like hemoglobin. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter: Hemoglobin [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like hemoglobin. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated timepoints for analysis of hematology parameter like MCH. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of MCH [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated timepoints for analysis for hematology parameter like MCH. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter: MCH [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like MCH. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter: MCH [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis of hematology parameter like MCH. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of MCV [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated timepoints for analysis for hematology parameter like MCV. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter: MCV [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter: MCV [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Hematology Parameter of Erythrocytes [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Hematology Parameter of Erythrocytes [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of the Hematology Parameter: Erythrocytes [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of the Hematology Parameter: Erythrocytes [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN), Carbon Dioxide (CO2), Chloride and Phosphorus [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH), Gamma-glutamyl Transferase (GGT), and Creatine Phosphokinase (CK) [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter like alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Chemistry Parameters of Lipase and Amylase [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Chemistry Parameters of Lipase and Amylase [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of of total protein, albumin and globulin. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total protein, albumin and globulin. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin [ Time Frame: Baseline and at Days 7, 14 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total protein, albumin and globulin. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Specific Gravity of Urine [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Specific Gravity of Urine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Specific Gravity of Urine [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Specific Gravity of Urine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Potential of Hydrogen (pH) of Urine [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of Urinary 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 acid pH (5.0 - 6.0). Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in pH of Urine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of Urinary 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 acid pH (5.0 - 6.0). Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of pH of Urine [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of Urinary 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 acid pH (5.0 - 6.0). Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of pH of Urine [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of Urinary 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 acid pH (5.0 - 6.0). Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Urine Urobilinogen [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Urine Urobilinogen [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Urine Urobilinogen [ Time Frame: Baseline and at Days 7, 14 ]
    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1.
  • Period 2: Absolute Values of Urine Urobilinogen [ Time Frame: Baseline and at Days 3, 7, 9 ]
    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Period 1 Day 14 for Period 2.
  • Period 1: Change From Baseline in Heart Rate [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose ]
    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Heart Rate [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Heart Rate [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Absolute Values of Heart Rate [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF) Interval, and Bazett QT Correction Formula (QTcB) Interval [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interal, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interal, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval [ Time Frame: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose ]
    Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 1: Change From Baseline in Temperature [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Temperature [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Temperature [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: Absolute Values of Temperature [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 1: Change From Baseline in Pulse Rate [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Pulse Rate [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Pulse Rate [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: Absolute Values of Pulse Rate [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 1: Change From Baseline in Respiratory Rate [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Respiratory Rate [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Respiratory Rate [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: Absolute Values of Respiratory Rate [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 1: Change From Baseline in Blood Pressure [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 2: Change From Baseline in Blood Pressure [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Period 1: Absolute Values of Blood Pressure [ Time Frame: Baseline and at Days 2, 3, 4, 5 and 7 ]
    SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: Absolute Values of Blood Pressure [ Time Frame: Baseline and at Days 4, 7, 9, and 10 ]
    SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
  • Period 2: AUC (0-tau) of GSK3640254 [ Time Frame: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Cmax of GSK3640254 [ Time Frame: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Ctau of GSK3640254 [ Time Frame: Pre-dose, 1 and 2 hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254 [ Time Frame: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Tmax of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Tmax of TAF [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Tmax of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Tmax of FTC [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 1: Tmax of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
  • Period 2: Tmax of TFV [ Time Frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7 ]
    Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Number of subjects with adverse events (AE) and serious adverse events (SAE) [ Time Frame: Up to Day 24 ]
    An AE is any untoward medical occurrence in a clinical study subject, 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: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed before.
  • Absolute values of the hematology parameters of platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the hematology parameters of hematocrit [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the hematology parameters of hemoglobin [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the hematology parameters of mean corpuscular hemoglobin [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the hematology parameters of mean corpuscular volume [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the hematology parameters of red blood cell count [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of hematocrit [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of hemoglobin [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of mean corpuscular hemoglobin [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of mean corpuscular volume [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Change from Baseline in hematology parameter of red blood cell count [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of hematology parameters.
  • Absolute values of the clinical chemistry parameter of glucose, calcium, potassium, sodium, blood urea nitrogen, carbon dioxide, chloride and phosphorus [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, gamma-glutamyl transferase, creatine phosphokinase, lipase and amylase [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of total protein, albumin and globulin [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of anion gap [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of total cholesterol [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of the clinical chemistry parameter of triglycerides [ Time Frame: Up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of glucose, calcium, potassium, sodium, blood urea nitrogen, carbon dioxide, chloride and phosphorus [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of alkaline phosphatase, ALT, AST, lactate dehydrogenase, gamma-glutamyl transferase, creatine phosphokinase, lipase and amylase [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of total protein, albumin and globulin [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of anion gap [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of total cholesterol [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Change from Baseline in clinical chemistry parameter of triglycerides [ Time Frame: Baseline and up to Day 23 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.
  • Absolute values of specific gravity of urine [ Time Frame: Up to Day 23 ]
    Urine samples will be collected for the assessment of urine parameters.
  • Absolute values of urine potential of hydrogen (pH) [ Time Frame: Up to Day 23 ]
    Urine samples will be collected for the assessment of urine parameters.
  • Absolute values of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase levels in urine [ Time Frame: Up to Day 23 ]
    Urine samples will be collected to detect the presence of glucose, protein, blood, ketone, bilirubin, urobilinogen, nitrite and leukocyte esterase using the dipstick method.
  • Change from Baseline in specific gravity of urine [ Time Frame: Baseline and up to Day 23 ]
    Urine samples will be collected for the assessment of urine parameters.
  • Change from Baseline in pH of urine [ Time Frame: Baseline and up to Day 23 ]
    Urine samples will be collected for the assessment of urine parameters.
  • Change from Baseline in glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte leukocyte esterase levels in the urine [ Time Frame: Baseline and up to Day 23 ]
    Urine samples will be collected to detect the presence of glucose, protein, blood, ketone, bilirubin, urobilinogen, nitrite and leukocyte esterase using the dipstick method.
  • Absolute values of electrocardiogram (ECG) parameters [ Time Frame: Up to Day 23 ]
    Twelve-lead ECGs will be performed with the subject in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine which will measure PR, QRS, QT, and corrected QT interval by Fridericia's formula (QTcF).
  • Change from Baseline in ECG parameters [ Time Frame: Baseline and up to Day 23 ]
    Twelve-lead ECGs will be performed with the subject in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine which will calculate heart rate and measure PR, QRS, QT, and QTcF intervals.
  • Absolute values of oral temperature [ Time Frame: Up to Day 24 ]
    Oral temperature will be assessed.
  • Absolute values of pulse rate [ Time Frame: Up to Day 24 ]
    Pulse rate will be assessed in a semi-recumbent position after 5 minutes of rest for the subject with an automated device.
  • Absolute values of respiratory rate [ Time Frame: Up to Day 24 ]
    Respiratory rate will be assessed.
  • Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Up to Day 24 ]
    SDP and DBP will be assessed in a semi-recumbent position after 5 minutes of rest for the subject with an automated device.
  • Change from Baseline in oral temperature [ Time Frame: Baseline and up to Day 24 ]
    Oral temperature will be assessed.
  • Change from Baseline in pulse rate [ Time Frame: Baseline and up to Day 24 ]
    Pulse rate will be assessed in a semi-recumbent position after 5 minutes of rest for the subject with an automated device.
  • Change from Baseline in respiratory rate [ Time Frame: Baseline and up to Day 24 ]
    Respiratory rate will be assessed.
  • Change from Baseline in SBP and DBP [ Time Frame: Baseline and up to Day 24 ]
    SDP and DBP will be assessed in a semi-recumbent position after 5 minutes of rest for the subject with an automated device.
  • AUC(0-tau) for GSK3640254 [ Time Frame: Days 2 to 6 and Day 7 (1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
  • Cmax for GSK3640254 [ Time Frame: Days 2 to 6 and Day 7 (1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
  • Ctau for GSK3640254 [ Time Frame: Days 2 to 6 and Day 7 (1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
  • Time of maximum observed concentration (Tmax) for GSK3640254 [ Time Frame: Days 2 to 6 and Day 7 (1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
  • Tmax for TAF [ Time Frame: Day2,3,4,5,6,7,8,9,10,11,12,13 and 14 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 1; Day 1,2,3,4,5,6 and 7 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TAF.
  • Tmax for FTC [ Time Frame: Day2,3,4,5,6,7,8,9,10,11,12,13 and 14 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 1; Day 1,2,3,4,5,6 and 7 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of FTC.
  • Tmax for TFV [ Time Frame: Day2,3,4,5,6,7,8,9,10,11,12,13 and 14 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 1; Day 1,2,3,4,5,6 and 7 (0.25,0.5,0.75minutes and 1,1.5,2,3,4,5,6,8,12 and 24hours post-dose) in Period 2 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of TFV.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine
Official Title  ICMJE An Open-Label One-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Subjects
Brief Summary Human immunodeficiency virus (HIV) infection frequently involves combination drug therapy for its treatment; hence, it is important to understand their interactions and resulting changes in exposure which are associated with medications. This is a Phase-1, open-label, fixed-sequence 2-period, one-way drug interaction study to assess the pharmacokinetic (PK), safety, and tolerability of GSK3640254 and Tenofovir alafenamide/emtricitabine (TAF/FTC) when administered alone and in combination in healthy subjects. The study will consist of a screening period of 28 days before the first dose of study intervention followed by 2 sequential treatment periods. Subjects will be administered TAF/FTC 25/200 milligram (mg) once daily (QD) on Days 1 to 14 of Period 1 followed by co-administration of TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 to 7 of Period 2.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
This is a fixed-sequence 2-period, one-way drug interaction study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Tenofovir alafenamide/emtricitabine
    TAF/FTC will be available as 25/200 milligrams (mg) tablet. Subjects will be administered TAF/FTC 25/200 mg QD via the oral route.
  • Drug: GSK3640254
    GSK3640254 will be available as 100 mg capsule. Subjects will be administered GSK3640254 200 mg capsule QD via the oral route.
Study Arms  ICMJE Experimental: TAF/FTC followed by TAF/FTC + GSK3640254
Subjects will receive TAF/FTC 25/200 mg QD on Days 1 through 14 in Treatment Period 1. Subjects will be co-administered TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Treatment Period 2.
Interventions:
  • Drug: Tenofovir alafenamide/emtricitabine
  • Drug: GSK3640254
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 7, 2019)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 30, 2019
Actual Primary Completion Date March 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
  • Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kilograms [kg] (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kilograms per meter square (kg/m^2) (inclusive).
  • Male or female; A female subject is eligible to participate if she is not pregnant, not breastfeeding and not a woman of childbearing potential (WOCBP).
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

Exclusion Criteria:

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (e.g.,gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism and/or excretion of the study drugs or render the subject unable to take oral study intervention.
  • Any history of significant underlying psychiatric disorder including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
  • Any history of major depressive disorder with or without suicidal features or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
  • Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
  • History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <80 milliliters per minute (mL/min). Creatinine clearance (CrCL) is estimated by either of the following methods: (a) The Modification of Diet in Renal Disease (MDRD) equation: estimated glomerular filtration rate (eGFR) (milliliter [mL]/minute [min]/1.73 meter square [m^2]) = 175 x (SCr)^-1.154 x (Age)^-0.203 x 0.742 [if female] x 1.212 [if African American] glomerular filtration rate (GFR) is expressed in mL/min/1.73 m^2, SCr is serum creatinine expressed in milligrams per deciliter (mg/dL), and age is expressed in years. (b)The Cockcroft-Gault equation: CrCL(mL/min) ={((l40-age) x weight)/(72xSCr)}x 0.85 (if female) CrCL is expressed in mL/min, age is expressed in years, weight is expressed in kg, and SCr is serum creatinine expressed in mg/dL.
  • Presence of Hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to starting study intervention.
  • Positive Hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention AND positive on reflex to Hepatitis C ribonucleic acid (RNA).
  • Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.
  • ALT >1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
  • Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
  • Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
  • A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and for the duration of the study.
  • Treatment with any vaccine within 30 days prior to receiving study intervention.
  • Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
  • Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia-Suicide Severity Rating Scale (C-SSRS).
  • Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the investigator or VH/GSK Medical Monitor, will interfere with the safety for the individual subject.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate for male: <45 or >100 beats per minute (bpm) and for females: <50 or >100 bpm; PR interval: <120 or >200 milliseconds (msec); QRS duration: <70 or >110 msec and QTcF interval for male: >450 msec and for female: >470 msec. A heart rate from 100 to 110 bpm can be rechecked by ECG or vital signs within 30 minutes to verify eligibility.
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
  • Regular use of tobacco- or nicotine-containing products within 3 months prior to Screening.
  • History of sensitivity to any of the study medications or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03836729
Other Study ID Numbers  ICMJE 208134
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP