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GSK investigating manufacturing site malfunction and assessing impact; Study 209713 Early Terminated due to risk of potential contamination of study tablets.
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This is an open-label, single-dose, four-period, four sequential, and crossover study conducted to assess the relative bioavailability of GSK3640254 mesylate tablets and GSK3640254 mesylate capsules (in the presence of a moderate fat meal). This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of GSK3640254 mesylate tablet formulation. 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 16 participants will be enrolled and the duration of the study will be approximately 54 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 - Treatment ABCD | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
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| Sequence 2 - Treatment BADC | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
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| Sequence 3 - Treatment CDAB | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3640254 Tablet | Drug | GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| AUC(0-infinity) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| AUC(0-t) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Maximum Observed Concentration (Cmax) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of study medication. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Austin | Texas | 78744 | United States |
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
A total of 16 participants were enrolled in this study. The study was early terminated by sponsor due to a potential contamination issue in the study drug after completion of treatment Period 2. Hence, treatment Periods 3 and 4 were not conducted.
This was a randomized, open-label, single dose, 4 period crossover study in healthy participants conducted at a single center in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 - Treatment ABCD | Participants received a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-reference) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-test) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between two treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-reference) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-test) on Day 1 in treatment Period 4. Treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| FG001 | Sequence 2 - Treatment BADC | Participants received a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between two treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| FG002 | Sequence 3 - Treatment CDAB | Participants received a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between 2 treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| FG003 | Sequence 4 - Treatment DCBA | Participants received a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between 2 treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (1 Day) |
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| Washout Period 1 (Up to 7 Days) |
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| Treatment Period 2 (1 Day) |
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| Washout Period 2 (Up to 7 Days) |
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| Treatment Period 3 (1 Day) |
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| Washout Period 3 (Up to 7 Days) |
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| Treatment Period 4 (1 Day) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1 - Treatment ABCD | Participants received a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-reference) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-test) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between two treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-reference) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-test) on Day 1 in treatment Period 4. Treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated. | PK Parameter Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
AEs and SAEs were collected from start of the treatment (Day 1) up to Day 14
Safety Population consisted of all participants who received at least 1 dose of study medication. Data is presented for Periods 1 and 2 only as data was not collected in Periods 3 and 4 due to early termination of the study following completion of Period 2.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A- GSK3640254 200 mg Capsules (Fed) | Participants received a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-reference) on Day 1 in treatment Period 1 or 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 30, 2019 | Jul 27, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 15, 2020 | Jul 27, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C000723722 | GSK3640254 |
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Eligible participants will be randomly assigned to 1 of 4 treatment sequences (ABCD, BADC, CDAB, or DCBA) in each treatment period.
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This is an open-label study.
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| Sequence 4 - Treatment DCBA | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
|
| GSK3640254 Capsule | Drug | GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. |
|
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. |
| Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Cmax for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Time of Cmax (Tmax) for GSK3640254 200 mg Capsules Under Fed Condition (Treatment A) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Time of Cmax (Tmax) for GSK3640254 200 mg Tablets Under Fed, Fasted and High Fat Condition (Treatment B, C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Up to Day 14 |
| Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. | Day 2 |
| Absolute Values for Hematology Parameter: Hemoglobin | Blood samples were collected to analyze the hematology parameter: hemoglobin. | Day 2 |
| Absolute Values for Hematology Parameter: Hematocrit | Blood samples were collected to analyze the hematology parameter: hematocrit. | Day 2 |
| Absolute Values for Hematology Parameter: Erythrocytes | Blood samples were collected to analyze the hematology parameter: erythrocytes. | Day 2 |
| Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. | Day 2 |
| Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. | Day 2 |
| Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen | Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. | Day 2 |
| Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase | Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. | Day 2 |
| Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin | Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. | Day 2 |
| Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein | Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. | Day 2 |
| Absolute Values for Chemistry Parameters: Amylase, Lipase | Blood samples were collected to analyze the chemistry parameters: amylase and lipase. | Day 2 |
| Absolute Values for Urine Parameter: Specific Gravity | Urine samples were collected to analyze the urine 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. | Day 2 |
| Absolute Values for Urine Parameter: Urobilinogen | Urine samples were collected to analyze the urine parameter: urobilinogen. | Day 2 |
| Absolute Values for Urine Parameter: Potential of Hydrogen (pH) | Urine samples were collected to analyze the urine 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). | Day 2 |
| Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF), Corrected QT Interval Using Bazett's Formula (QTcB) | Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. | Day 1: 2 hours and 4 hours |
| Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. | Days 2, 3, 4, and 5 |
| Absolute Values for Pulse Rate | Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. | Days 2, 3, 4, and 5 |
| Absolute Values for Respiratory Rate | Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. | Days 2, 3, 4, and 5 |
| Absolute Values for Body Temperature | Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. | Days 2, 3, 4, and 5 |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Hematology Parameter: Hemoglobin | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Hematology Parameter: Hematocrit | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Hematology Parameter: Erythrocytes | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen | Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase | Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin | Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein | Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Chemistry Parameters: Amylase, Lipase | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Urinalysis Parameter: Specific Gravity | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Urinalysis Parameter: Urobilinogen | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in Urinalysis Parameter: pH | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day -1) and at Day 2 |
| Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB | Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day 1, Pre-dose), Day 1: 2 hours and 4 hours |
| Change From Baseline in SBP and DBP | SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
| Change From Baseline in Pulse Rate | Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
| Change From Baseline in Respiratory Rate | Respiratory rate was measured in the semi-recumbent position 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, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
| Change From Baseline in Body Temperature | Body temperature was measured in the semi-recumbent position 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, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
| Lag Time for Absorption (Tlag) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Apparent Terminal Phase Half-life (t1/2) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Apparent Oral Clearance (CL/F) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Apparent Volume of Distribution (Vz/F) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetic Concentration of GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK Concentration Population included all participants who underwent plasma PK sampling and had evaluable PK assay results. | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Sequence 2 - Treatment BADC | Participants received a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between two treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| BG002 | Sequence 3 - Treatment CDAB | Participants received a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between 2 treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| BG003 | Sequence 4 - Treatment DCBA | Participants received a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-Test) on Day 1 in treatment Period 1; followed by a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-Reference) on Day 1 in treatment Period 2. There was a washout period of at least 7 days between 2 treatment periods. Participants were planned to receive a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-Test) on Day 1 in treatment Period 3; and a single dose of GSK3640254 200 mg capsules, orally under moderate fat conditions (Treatment A-Reference) on Day 1 in treatment Period 4. The treatment Periods 3 and 4 were planned but no participants were enrolled due to early termination of the study. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Treatment B- GSK3640254 200 mg Tablet (Fed) | Participants received a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-test) on Day 1 in treatment Period 1 or 2. |
|
|
|
| Primary | AUC(0-infinity) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
|
| Primary | AUC(0-t) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Primary | Maximum Observed Concentration (Cmax) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
|
| Primary | Cmax for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Primary | Time of Cmax (Tmax) for GSK3640254 200 mg Capsules Under Fed Condition (Treatment A) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. | Posted | Median | Full Range | Hours | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Primary | Time of Cmax (Tmax) for GSK3640254 200 mg Tablets Under Fed, Fasted and High Fat Condition (Treatment B, C and D) | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | Full Range | Hours | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
|
| Secondary | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of study medication. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 14 |
|
|
|
| Secondary | Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. | Safety Population. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Hematology Parameter: Hemoglobin | Blood samples were collected to analyze the hematology parameter: hemoglobin. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Hematology Parameter: Hematocrit | Blood samples were collected to analyze the hematology parameter: hematocrit. | Safety Population. | Posted | Mean | Standard Deviation | Proportion of red blood cells in blood | Day 2 |
|
|
|
| Secondary | Absolute Values for Hematology Parameter: Erythrocytes | Blood samples were collected to analyze the hematology parameter: erythrocytes. | Safety Population. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. | Safety Population. | Posted | Mean | Standard Deviation | Femtoliter | Day 2 |
|
|
|
| Secondary | Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. | Safety Population. | Posted | Mean | Standard Deviation | Picograms | Day 2 |
|
|
|
| Secondary | Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen | Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. | Safety Population. | Posted | Mean | Standard Deviation | Millimoles per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase | Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. | Safety Population. | Posted | Mean | Standard Deviation | International units per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin | Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein | Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Chemistry Parameters: Amylase, Lipase | Blood samples were collected to analyze the chemistry parameters: amylase and lipase. | Safety Population. | Posted | Mean | Standard Deviation | Units per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Urine Parameter: Specific Gravity | Urine samples were collected to analyze the urine 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. | Safety Population. | Posted | Mean | Standard Deviation | Ratio | Day 2 |
|
|
|
| Secondary | Absolute Values for Urine Parameter: Urobilinogen | Urine samples were collected to analyze the urine parameter: urobilinogen. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter | Day 2 |
|
|
|
| Secondary | Absolute Values for Urine Parameter: Potential of Hydrogen (pH) | Urine samples were collected to analyze the urine 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). | Safety Population. | Posted | Mean | Standard Deviation | pH | Day 2 |
|
|
|
| Secondary | Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF), Corrected QT Interval Using Bazett's Formula (QTcB) | Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. | Safety Population. | Posted | Mean | Standard Deviation | Milliseconds | Day 1: 2 hours and 4 hours |
|
|
|
| Secondary | Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury | Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Absolute Values for Pulse Rate | Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Absolute Values for Respiratory Rate | Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. | Safety Population. | Posted | Mean | Standard Deviation | Breaths per minute | Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Absolute Values for Body Temperature | Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. | Safety Population. | Posted | Mean | Standard Deviation | Degrees Celsius | Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count | Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameter: Hemoglobin | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameter: Hematocrit | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Proportion of red blood cells in blood | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Femtoliter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Picograms | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen | Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Millimoles per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase | Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | International units per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin | Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein | Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Chemistry Parameters: Amylase, Lipase | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Units per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Urinalysis Parameter: Specific Gravity | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Ratio | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Urinalysis Parameter: Urobilinogen | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in Urinalysis Parameter: pH | 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, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | pH | Baseline (Day -1) and at Day 2 |
|
|
|
| Secondary | Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB | Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Milliseconds | Baseline (Day 1, Pre-dose), Day 1: 2 hours and 4 hours |
|
|
|
| Secondary | Change From Baseline in SBP and DBP | SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Change From Baseline in Pulse Rate | Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Change From Baseline in Respiratory Rate | Respiratory rate was measured in the semi-recumbent position 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, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Change From Baseline in Body Temperature | Body temperature was measured in the semi-recumbent position 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, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. | Safety Population. | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5 |
|
|
|
| Secondary | Lag Time for Absorption (Tlag) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | Full Range | Hours | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Apparent Terminal Phase Half-life (t1/2) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Apparent Oral Clearance (CL/F) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz/F) for GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. | PK Parameter Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetic Concentration of GSK3640254 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK Concentration Population included all participants who underwent plasma PK sampling and had evaluable PK assay results. | PK Concentration Population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Nanogram per milliliter | Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Treatment B- GSK3640254 200 mg Tablet (Fed) | Participants received a single dose of GSK3640254 200 mg tablets, orally under moderate fat conditions (Treatment B-test) on Day 1 in treatment Period 1 or 2. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG002 | Treatment C- GSK3640254 200 mg Tablet (Fasted) | Participants received a single dose of GSK3640254 200 mg tablets, orally under fasted conditions (Treatment C-reference) on Day 1 in treatment Period 1 or 2. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG003 | Treatment D- GSK3640254 200 mg Tablet (High Fat) | Participants received a single dose of GSK3640254 200 mg tablets, orally under high fat conditions (Treatment D-test) on Day 1 in treatment Period 1 or 2. | 0 | 8 | 0 | 8 | 1 | 8 |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012897 | Slow Virus Diseases |
| Wilcoxon rank sum test |
| 0.3125 |
The p-value was assessed based on the Wilcoxon rank sum test. |
| Median Difference (Final Values) |
| 1.000 |
| 2-Sided |
| 90 |
| -0.7500 |
| 5.2500 |
The median difference and the 90% confidence interval of the median difference were estimated from Hodges-Lehmann estimate. |
| Other |
| Any SAEs |
|
| Eosinophils |
|
| Lymphocytes |
|
| Monocytes |
|
| Neutrophils |
|
| Platelet count |
|
| Cholesterol |
|
| Triglycerides |
|
| Anion gap |
|
| Calcium |
|
| Carbon dioxide |
|
| Chloride |
|
| Phosphate |
|
| Potassium |
|
| Sodium |
|
| Blood urea nitrogen |
|
| Lactate dehydrogenase |
|
| ALT |
|
| ALP |
|
| AST |
|
| Gamma-glutamyl transferase |
|
| Creatinine |
|
| Bilirubin |
|
| Direct bilirubin |
|
| Globulin |
|
| Protein |
|
| Lipase |
|
| PR Interval: Day 1, 4 hours |
|
| QRS Duration: Day 1, 2 hours |
|
| QRS Duration: Day 1, 4 hours |
|
| QT Interval: Day 1, 2 hours |
|
| QT Interval: Day 1, 4 hours |
|
| QTcF Interval: Day 1, 2 hours |
|
| QTcF Interval: Day 1, 4 hours |
|
| QTcB Interval: Day 1, 2 hours |
|
| QTcB Interval: Day 1, 4 hours |
|
| SBP: Day 3 |
|
| SBP: Day 4 |
|
| SBP: Day 5 |
|
| DBP: Day 2 |
|
| DBP: Day 3 |
|
| DBP: Day 4 |
|
| DBP: Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Eosinophils |
|
| Lymphocytes |
|
| Monocytes |
|
| Neutrophils |
|
| Platelet count |
|
| Cholesterol |
|
| Triglycerides |
|
| Anion gap |
|
| Calcium |
|
| Carbon dioxide |
|
| Chloride |
|
| Phosphate |
|
| Potassium |
|
| Sodium |
|
| Blood urea nitrogen |
|
| Lactate dehydrogenase |
|
| ALT |
|
| ALP |
|
| AST |
|
| Gamma-glutamyl transferase |
|
| Creatinine |
|
| Bilirubin |
|
| Direct bilirubin |
|
| Globulin |
|
| Protein |
|
| Lipase |
|
| PR Interval: Day 1, 4 hours |
|
| QRS Duration: Day 1, 2 hours |
|
| QRS Duration: Day 1, 4 hours |
|
| QT Interval: Day 1, 2 hours |
|
| QT Interval: Day 1, 4 hours |
|
| QTcF Interval: Day 1, 2 hours |
|
| QTcF Interval: Day 1, 4 hours |
|
| QTcB Interval: Day 1, 2 hours |
|
| QTcB Interval: Day 1, 4 hours |
|
| SBP: Day 3 |
|
| SBP: Day 4 |
|
| SBP: Day 5 |
|
| DBP: Day 2 |
|
| DBP: Day 3 |
|
| DBP: Day 4 |
|
| DBP: Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| 1 hour |
|
| 1.5 hours |
|
| 2 hours |
|
| 2.5 hours |
|
| 3 hours |
|
| 3.5 hours |
|
| 4 hours |
|
| 4.5 hours |
|
| 5 hours |
|
| 6 hours |
|
| 8 hours |
|
| 12 hours |
|
| 24 hours |
|
| 48 hours |
|
| 72 hours |
|
| 96 hours |
|