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A Proof of Concept Study of GSK3640254 in Human Immunodeficiency Virus-1 (HIV-1) Infected Treatment-naive Adults

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: NCT03784079
Recruitment Status : Completed
First Posted : December 21, 2018
Results First Posted : February 16, 2021
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Study Description
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Brief Summary:
Infection with HIV-1 continues to be a serious health threat throughout the world. Chronic exposure to combination anti-retroviral therapy identified anti-retroviral associated long-term toxicities. Hence, there is a need to prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 Maturation Inhibitor (MI) which may be effective for HIV-1 infection. This study will evaluate the antiviral effect, safety, tolerability and pharmacokinetics/ pharmacodynamics of GSK3640254 in HIV-1 infected treatment-naive adults. This study will consists of two parts; Part 1 and Part 2. Part 1 will evaluate two active doses of GSK3640254, 200 milligrams (mg) (Cohort 1) and 10 mg (Cohort 2) along with placebo to match GSK3640254 Mesylate salt. Part 2 will evaluate three active doses of GSK3640254. Dose level 1 of GSK3640254 that can provide at least 30 percent of the maximum effect (Cohort 1), dose level 2 of GSK3640254 that can provide at least 75 percent of the maximum effect (Cohort 2) and dose level 3 of GSK3640254 that can provide at least 90 percent of the maximum effect (Cohort 3). These doses are anticipated to be 5 mg, 40 mg and 100 mg respectively, but could be modified based on data obtained in Part 1. Subjects will also receive placebo to match GSK3640254 Mesylate salt in Part 2 of the study. All doses will be administered after a moderate fat meal. This study will consist of Screening period (up to 14 days), Treatment period (Day 1- Day 10), post-dose Follow-up (Day 11- Day 17) and final Follow-up (Day 18-24). A total of approximately 34 subjects will be enrolled, of which, 14 subjects will be randomized in Part 1 and 20 in Part 2 of the study. Six subjects will be enrolled in each of the active dose cohorts and 2 subjects will be enrolled in each of the placebo cohorts.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: GSK3640254 Drug: Placebo matching GSK3640254 Mesylate salt Phase 2

Study Design
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Eligible subjects will be randomized to receive two active doses of GSK3640254 along with placebo in Part 1 of the study. In Part 2, subjects will receive three active doses of GSK3640254 along with placebo depending upon the data obtained in Part 1.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double blind study. Subjects and investigator will be blinded.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults
Actual Study Start Date : January 31, 2019
Actual Primary Completion Date : February 6, 2020
Actual Study Completion Date : February 6, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: GSK3640254 10 mg
Participants will receive GSK3640254 10 milligram (mg), capsules, orally for 10 days.
 Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 1: GSK3640254 200 mg
Participants will receive GSK3640254 200 mg, capsules, orally for 10 days.
 Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Placebo Comparator: Part 1: Placebo
Participants will receive placebo capsules, orally for 10 days.
 Drug: Placebo matching GSK3640254 Mesylate salt
Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water
Experimental: Part 2: GSK3640254 40 mg
Participants will receive GSK3640254 40 mg, capsules, orally for 7 days.
 Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 2: GSK3640254 80 mg
Participants will receive GSK3640254 80 mg, capsules, orally for 7 days.
 Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 2: GSK3640254 140 mg
Participants will receive GSK3640254 140 mg, capsules, orally for 7 days.
 Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Placebo Comparator: Part 2: Placebo
Participants will receive placebo capsules, orally for 7 days.
 Drug: Placebo matching GSK3640254 Mesylate salt
Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11 [ Time Frame: Baseline (Day 1) and Day 11 ]
    Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  2. Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at Day 8 [ Time Frame: Baseline (Day 1) and Day 8 ]
    Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.


Secondary Outcome Measures :
  1. Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 24 ]
    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. 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 or other situations as per Medical or scientific judgment. Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.

  2. Part 2: Number of Participants With Non-SAEs and SAEs [ Time Frame: Up to Day 12 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. 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 or other situations as per Medical or scientific judgment.

  3. Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  4. Part 1: Change From Baseline in Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  5. Part 1: Change From Baseline in Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  6. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  7. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  8. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  9. Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythrocyte (erythro). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  10. Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  11. Part 2: Change From Baseline in Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  12. Part 2: Change From Baseline in Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  13. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  14. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  15. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  16. Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  17. Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  18. Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  19. Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  20. Part 1: Change From Baseline in Chemistry Parameters: Protein [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  21. Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase [ Time Frame: Baseline (Day 1) and Visit 6 (Day 11) ]
    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  22. Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  23. Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  24. Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  25. Part 2: Change From Baseline in Chemistry Parameters: Protein [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  26. Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  27. Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  28. Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  29. Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  30. Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  31. Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  32. Part 2: Change From Baseline in Urinalysis Parameter: pH [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  33. Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  34. Part 1: Change From Baseline in Respiratory Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  35. Part 1: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  36. Part 2: Change From Baseline in SBP and DBP [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  37. Part 2: Change From Baseline in Respiratory Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  38. Part 2: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  39. Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF) [ Time Frame: Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours) ]
    Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  40. Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF [ Time Frame: Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours) ]
    Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  41. Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  42. Part 1: Absolute Values for Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  43. Part 1: Absolute Values for Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  44. Part 1: Absolute Values for Hematology Parameter: Erythrocytes [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  45. Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  46. Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  47. Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  48. Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  49. Part 2: Absolute Values for Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  50. Part 2: Absolute Values for Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  51. Part 2: Absolute Values for Hematology Parameter: Erythrocytes [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  52. Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  53. Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  54. Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  55. Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  56. Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  57. Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  58. Part 1: Absolute Values for Chemistry Parameters: Protein [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  59. Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase [ Time Frame: Baseline (Day 1) and Visit 6 (Day 11) ]
    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  60. Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  61. Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  62. Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  63. Part 2: Absolute Values for Chemistry Parameters: Protein [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  64. Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  65. Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  66. Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  67. Part 1: Absolute Values for Urinalysis Parameter: pH [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  68. Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  69. Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  70. Part 2: Absolute Values for Urinalysis Parameter: pH [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  71. Part 1: Absolute Values for SBP and DBP [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  72. Part 1: Absolute Values for Respiratory Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  73. Part 1: Absolute Values for Pulse Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Days 8 to 10) ]
    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  74. Part 2: Absolute Values for SBP and DBP [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  75. Part 2: Absolute Values for Respiratory Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  76. Part 2: Absolute Values for Pulse Rate [ Time Frame: Baseline (Day 1) and Visit 5 (Day 7) ]
    Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  77. Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals [ Time Frame: Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours) ]
    Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  78. Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals [ Time Frame: Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours) ]
    Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  79. Part 1: Area Under the Plasma Concentration Time Curve From Zero to 24 (AUC[0-24]) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population consisted of all participants who received GSK3640254 and underwent plasma PK sampling during the study.

  80. Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  81. Part 1: Time to Maximum Observed Concentration (Tmax) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  82. Part 1: Concentration at 24 Hours Post-dose (C24) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  83. Part 1: Absorption Lag Time (Tlag) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  84. Part 2: AUC(0-24) Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  85. Part 2: Cmax Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  86. Part 2: Tmax Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  87. Part 2: C24 Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  88. Part 2: Tlag Following Administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  89. Part 1: Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  90. Part 1: Cmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  91. Part 1: Tmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  92. Part 1: Pre-dose Concentration (C0) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose ]
    Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  93. Part 1: Concentration at End of Dosing Interval (Ctau) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  94. Part 1: Apparent Terminal Phase Half-life (t1/2) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  95. Part 1: Apparent Oral Clearance (CL/F) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  96. Part 2: AUC(0-tau) Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  97. Part 2: Cmax Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  98. Part 2: Tmax Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  99. Part 2: C0 Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose ]
    Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  100. Part 2: Ctau Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  101. Part 2: t1/2 Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  102. Part 2: CL/F Following Repeat Dose Administration of GSK3640254 on Day 7 [ Time Frame: Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

  103. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau) [ Time Frame: Baseline (Day 1) and Day 8 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (AUC) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). PK/PD Population consisted of participants who met criteria for Per-Protocol and Pharmacokinetic Population analysis sets and who underwent PD sampling during the study.

  104. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax [ Time Frame: Baseline (Day 1) and Day 8 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Cmax) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.

  105. Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau [ Time Frame: Baseline (Day 1) and Day 8 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Ctau) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.

  106. Part 1: Accumulation Ratio Following Repeat Dose Administration of GSK3640254 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC equal to (=) AUC(0-tau) Days 8 to 10 divided by (/) AUC(0-24) Day 1; Ro_Cmax=Cmax Days 8 to 10/Cmax Day 1; and Ro_Ctau=Ctau Days 8 to 10/C24 Day 1.

  107. Part 2: Accumulation Ratio Following Repeat Dose Administration of GSK3640254 [ Time Frame: Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC=AUC(0-tau) Day 7/AUC(0-24) Day 1; Ro_Cmax=Cmax Day 7/Cmax Day 1; and Ro_Ctau=Ctau Day 7/C24 Day 1.

  108. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on AUC(0-24) [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  109. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on Cmax [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  110. Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on C24 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  111. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on AUC(0-tau) [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  112. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Cmax [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

  113. Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Ctau [ Time Frame: Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
  • Screening Cluster of designation 4 positive (CD4+) T-cell count >=350 cells per millimeter cube (cells/mm^3).
  • Documented HIV infection and Screening plasma HIV-1 RNA >=5000 copies/milliliter (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
  • Treatment-naive: No anti-retrovirals (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
  • Body weight >=50.0 kilograms (kg) (110 Pounds) for men and >=45.0 kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter square (kg/m^2) (inclusive).
  • 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.
  • For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment.
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment and positive on reflex to Hepatitis C RNA.
  • ALT >2 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Subjects with primary HIV infection, evidenced by acute retroviral syndrome (example given [e.g.], fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
  • 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 anatomy or motility (e.g., gastroesophageal reflux disease [GERD], 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 treatment.
  • Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
  • Any Grade 2-4 laboratory abnormality at screen, 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 lab abnormality is allowed within a single screening period to determine eligibility.
  • 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 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.
  • The subject has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.
  • Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered Columbia Suicide Severity Rating Scale (CSSRS).
  • Any positive result for illicit drug use (e.g., cocaine, heroin) at Screening. A positive screen for marijuana is not exclusionary, though if positive for delta-9-tetrahydrocannabinol (THC).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
  • Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject prior to randomization.
  • Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
  • An active Center for Disease Control and Prevention (CDC) Category C disease except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
  • Treatment with any vaccine within 30 days prior to receiving study medication.
  • Exclusion criteria for screening electrocardiogram (a single repeat is allowed for eligibility determination): Heart rate of <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR Interval of <120 or >200 milliseconds (msec) for both males and females; QRS duration of <70 or >110 msec for both males and females; QT interval corrected (QTc) for heart rate according to Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females. A heart rate from 100 to 110 bpm can be rechecked by electrocardiogram or vitals within 30 minutes to verify eligibility. QTcF is either machine read or manually over-read.
  • Any significant arrhythmia or electrocardiogram finding (e.g., prior myocardial infarction, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the Investigator OR ViiV Medical Monitor, will interfere with the safety for the individual subject.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03784079


Locations
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United States, California
GSK Investigational Site
Bakersfield, California, United States, 93301
United States, Florida
GSK Investigational Site
Orlando, Florida, United States, 32803
France
GSK Investigational Site
Marseille, France, 13003
GSK Investigational Site
Paris, France, 75018
GSK Investigational Site
Tourcoing cedex, France, 59208
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 81675
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60590
Italy
GSK Investigational Site
Roma, Lazio, Italy, 00149
GSK Investigational Site
Milano, Lombardia, Italy, 20127
GSK Investigational Site
Milano, Lombardia, Italy, 20157
South Africa
GSK Investigational Site
Johannesburg, Gauteng, South Africa, 2113
GSK Investigational Site
Bloemfontein, South Africa, 9301
GSK Investigational Site
Durban, South Africa, 4001
Spain
GSK Investigational Site
Alicante, Spain, 03010
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Barcelona, Spain, 08025
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Barcelona, Spain, 08907
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Sevilla, Spain, 41013
Sponsors and Collaborators
ViiV Healthcare
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare
  Study Documents (Full-Text)

Documents provided by ViiV Healthcare:
Study Protocol  [PDF] August 26, 2019
Statistical Analysis Plan  [PDF] February 6, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03784079    
Other Study ID Numbers: 208132
First Posted: December 21, 2018    Key Record Dates
Results First Posted: February 16, 2021
Last Update Posted: February 16, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
HIV-1, Antiviral Effect, GSK3640254, Proof of Concept
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
 Retroviridae Infections
RNA Virus Infections
Virus Diseases
Genital Diseases
Urogenital Diseases
Immunologic Deficiency Syndromes
Immune System Diseases