A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule

• Registration Number: NCT04263142
• Lead Sponsor: ViiV Healthcare

Brief Summary

This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-27
• Study First Submitted: 2020-02-06
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-10
• Primary Completion: 2020-03-24
• Study Completion: 2020-03-24
• Status Verified: 2021-02
• Results First Submitted: 2021-02-09
• Results First Submitted QC: 2021-02-09
• Last Update Submitted: 2021-02-09
• Results First Posted: 2021-03-03
• Last Update Posted: 2021-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1: Treatment AB	GSK3640254 Tablet	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 AB	GSK3640254 Capsule	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	GSK3640254 Tablet	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 1: Treatment BA	GSK3640254 Capsule	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	GSK3640254 Tablet	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	GSK3640254 Tablet	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	GSK3640254 Tablet	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.

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Maximum Observed Concentration (Cmax) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to Inf) for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to t) for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Cmax for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With AEs and SAEs-Part 2	Up to Day 19	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 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 or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1	Up to Day 12	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 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 or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Absolute Values for Erythrocytes Count-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocytes count.
Absolute Values for Hemoglobin-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hemoglobin.
Absolute Values for Hematocrit-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hematocrit.
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume.
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin.
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Absolute Values for Erythrocytes Count-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocytes count.
Absolute Values for Hemoglobin-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hemoglobin.
Absolute Values for Hematocrit-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hematocrit.
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocytes Count-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Hemoglobin-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hemoglobin. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Hematocrit-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocytes Count-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Hemoglobin-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hemoglobin. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Hematocrit-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate.
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, Blood Urea Nitrogen (BUN), Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide.
Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH.
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein.
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase.
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate.
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide.
Absolute Values for Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH.
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein.
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase.
Change From Baseline Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 1	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 2	Baseline (Day -1), Day 2 and Day 5	Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Absolute Values for Urine Parameter: Specific Gravity-Part 1	Baseline (Day -1), Day 2 and Day 5	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, indicated as ratio of urine density to water density.
Absolute Values for Urine Parameter: Urobilinogen-Part 1	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine urobilinogen.
Absolute Values for Urine Parameter: Potential of Hydrogen (pH)-Part 1	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0).
Absolute Values for Urine Parameter: Specific Gravity-Part 2	Baseline (Day -1), Day 2 and Day 5	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, indicated as ratio of urine density to water density.
Absolute Values for Urine Parameter: Urobilinogen-Part 2	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine urobilinogen.
Absolute Values for Urine Parameter: pH-Part 2	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0).
Change From Baseline in Urine Parameter: Specific Gravity-Part 1	Baseline (Day -1), Day 2 and Day 5	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, indicated as ratio of urine density to water density. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Urine Parameter: Urobilinogen-Part 1	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Urine Parameter: pH-Part 1	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Urine Parameter: Specific Gravity-Part 2	Baseline (Day -1), Day 2 and Day 5	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, indicated as ratio of urine density to water density. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Urine Parameter: Urobilinogen-Part 2	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Urine Parameter: pH-Part 2	Baseline (Day -1), Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Number of Participants With Abnormal Urine Dipstick Results-Part 1	Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of following urine parameters: bilirubin, glucose, ketones, nitrite, leukocyte esterase, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Only parameters and time points with abnormal results have been presented.
Number of Participants With Abnormal Urine Dipstick Results-Part 2	Day 2 and Day 5	Urine samples were collected at indicated time points for the assessment of following urine parameters: bilirubin, glucose, ketones, nitrite, leukocyte esterase, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Only parameters and time points with abnormal results have been presented.
Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)-Part 1	Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5	Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals.
Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2	Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5	Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals.
Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 1	Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5	Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2	Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5	Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Absolute Values for Vital Sign: Pulse Rate-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Pulse rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Absolute Values for Vital Sign: Temperature-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change From Baseline in Vital Sign: Temperature-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Vital Signs: SBP and DBP-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Blood pressure was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Vital Sign: Pulse Rate-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Pulse rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Absolute Values for Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Blood pressure was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Absolute Values for Vital Sign: Respiratory Rate-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Absolute Values for Vital Sign: Temperature-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Absolute Values for Vital Sign: Respiratory Rate-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change From Baseline in Vital Signs: SBP and DBP-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Blood pressure was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Absolute Values for Vital Signs: DBP and SBP-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Blood pressure was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Absolute Values for Vital Sign: Pulse Rate-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Pulse rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change From Baseline in Vital Sign: Pulse Rate-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Pulse rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change From Baseline in Vital Sign: Respiratory Rate-Part 1	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Vital Sign: Respiratory Rate-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Vital Sign: Temperature-Part 2	Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5	Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Lag Time for Absorption (Tlag) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Apparent Terminal Phase Half-life (t1/2) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Apparent Oral Clearance (CL/F) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Apparent Volume of Distribution (Vz/F) for GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Plasma Concentration of GSK3640254-Part 1	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis.
Tlag for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
T1/2 for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
CL/F for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Vz/F for GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Plasma Concentration of GSK3640254-Part 2	pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose	Blood samples were collected at indicated time points for PK analysis.

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Austin, Texas, United States