HIV Infections
Conditions
Keywords
Acquired Immunodeficiency Syndrome, First-time-in-human, Pharmacokinetics, Safety, Tolerability
Brief summary
This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1 and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and PK parameters of the tablet formulation when administered under fasting and fed conditions.
Interventions
DRUGGSK3739937 (PIB)
GSK3739937 will be administered as oral suspension.
DRUGPlacebo
Placebo will be given orally during each dosing day.
DRUGGSK3739937 (Tablet)
GSK3739937 Tablet will be administered via oral route.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double-blind study with participants and the site-staff blinded and sponsor unblended. Part 3 of the study will be open-label.
Intervention model description
Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent. * Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG). * Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and (re-)admission to the Phase I unit, using an approved molecular test polymerase chain reaction (PCR). * Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions. * Body weight \>=50.0 kilograms (kg) (110 pound \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilogram per square meter (kg/m\^2). * Male participants are eligible to participate if they agree to use contraceptive methods * A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP). - Capable of giving signed informed consent
Exclusion criteria
* Signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of inpatient admission. * Contact with known COVID-19 positive persons in the 14 days prior to inpatient admission. * History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, distribution, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data. * Pre-existing clinically relevant, in the opinion of the principal investigator (PI), gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms. * Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome. * Any known or suspected pre-existing psychiatric condition * Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS) at screening . * Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug. * Estimated glomerular filtration rate (eGFR) \<90 milliliters/minute (mL/min) or serum creatinine \>1.1 x upper limit of normal (ULN). * Hemoglobin \<12.5 grams/deciliter (g/dL) for men and \<11 g/dL for women. * ALT or AST \>1.1x ULN. * Bilirubin \>1.1 x ULN (isolated bilirubin \>1.1 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) * Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months (does not include ST segment changes associated with repolarization), symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia (\>=3 consecutive ventricular ectopic beats), second-degree atrioventricular (AV) block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality (including but not specific to left or right complete bundle branch; AV block \[2nd degree or higher\]; Wolff-Parkinson-White \[WPW\] syndrome), Sinus Pauses \> 3 seconds, which, in the opinion of the investigator or ViiV Healthcare (VH)/ GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual participant. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameter - Hematocrit | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Up to 27 weeks | Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline. |
| Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Up to 5 weeks | Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline. |
| Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Up to 16 weeks | Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline. |
| Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day 1, pre-dose) and Day 6 | Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day 1, pre-dose) and Day 14 | Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day 1, pre-dose) and Day 15 | Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day 1, pre-dose) and Day 6 | Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Vital Signs - Pulse Rate | Baseline (Day 1, pre-dose) and Day 6 | Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate | Baseline (Day 1, pre-dose) and Day 14 | Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate | Baseline (Day 1, pre-dose) and Day 15 | Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Vital Signs - Pulse Rate | Baseline (Day 1, pre-dose) and Day 6 | Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Vital Signs - Body Temperature | Baseline (Day 1, pre-dose) and Day 6 | Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature | Baseline (Day 1, pre-dose) and Day 14 | Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature | Baseline (Day 1, pre-dose) and Day 15 | Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Vital Signs - Body Temperature | Baseline (Day 1, pre-dose) and Day 6 | Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | Baseline (Day 1, pre-dose) and Day 6 | Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate | Baseline (Day 1, pre-dose) and Day 14 | Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate | Baseline (Day 1, pre-dose) and Day 15 | Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Vital Signs - Respiratory Rate | Baseline (Day 1, pre-dose) and Day 6 | Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Up to 27 weeks | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented. |
| Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Up to 5 weeks | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented. |
| Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Up to 16 weeks | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented. |
| Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937 | Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 27 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: 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 important medical events may jeopardize the participant or may require medical or surgical intervention/Standard of care (SOC) to prevent one of the other outcomes mentioned before. |
| Part 2 - Number of Any AEs and SAEs | Up to 5 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: 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 important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. |
| Part 3 - Number of Any AEs and SAEs | Up to 16 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: 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 important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. |
| Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline (Day 1, pre-dose) and Day 15 | Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | Baseline (Day -1) and Day 6 | Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
| Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count | Baseline (Day 1, pre-dose) and Day 14 | Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period. | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis |
| Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1 | Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1 | Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - C24 of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) Clast of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - Tmax of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - T1/2 of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - Tlag of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - Tlast of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 3 (Cohort 7) - CL/F of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937 | Up to day 16 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. |
| Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937 | Up to day 16 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 10 mg, 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. |
| Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937 | Up to day 33 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. |
| Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937 | Up to day 33 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. |
| Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937 | Up to day 33 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. |
| Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 AUC(0-tau) / day 1 AUC(0-tau). |
| Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 AUC(0-tau) / day 1 AUC(0-tau). |
| Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 AUC(0-tau) / day 1 AUC(0-tau). |
| Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 Cmax / day 1 Cmax. |
| Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Actual measure type is Ratio. Accumulation ratio calculated as the ratio of day 18 Cmax / day 1 Cmax. |
| Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 Cmax / day 1 Cmax. |
| Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 C(Tau) / day 1 C(Tau). |
| Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 C(Tau) / day 1 C(Tau). |
| Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU]) | Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 C(Tau) / day 1 C(Tau). |
| Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937 | Up to day 15 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohorts 3 and 4, steady-state GSK3739937 concentrations was assessed by estimating the slope of concentrations on pre-dose assessments on Days 2-14 (Part 2 cohort 3 and 4) and the day 15 (24-hr post-dose relative to dosing on day 14). PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937 | Up to day 19 | Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohort 5, steady state GSK3739937 concentrations was assessed by estimating the slope of the concentrations of pre-dose assessments on Days 2-18 and the day 19 (24-hr post-dose relative to dosing on day 18). PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period | Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. |
Countries
United States
Participant flow
Recruitment details
This study includes 3 parts. In part 1, 34 participants were randomized. In part 2, 40 participants were randomized. In part 3, 17 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (Cohort 1) - Single Dose (SD) Placebo (PBO)/GSK3739937 SD 80 mg/GSK3739937 SD 320 mg Participants received single oral dose of placebo as suspension in Treatment Period 1, followed by single oral dose of 80 milligrams (mg) of GSK3739937 in Treatment Period 2, and followed by single oral dose of 320 mg of GSK3739937 in Treatment Period 3. | 6 |
| Part 1 (Cohort 1) - GSK3739937 SD 10 mg/ SD PBO/ GSK3739937 SD 320 mg Participants received single oral dose of 10 mg of GSK3739937 as suspension in Treatment Period 1, followed by single oral dose of placebo as suspension in Treatment Period 2, and followed by single oral dose of 320 mg of GSK3739937 as suspension in Treatment Period 3. | 3 |
| Part 1 (Cohort 1) - GSK3739937 SD 10 mg/ GSK3739937 SD 80 mg/SD PBO Participants received single oral dose of 10 mg of GSK3739937 as suspension in Treatment Period 1, followed by single oral dose of 80 mg of GSK3739937 as suspension in Treatment Period 2, and followed by single oral dose of placebo as suspension in Treatment Period 3. | 4 |
| Part 1 (Cohort 1) - GSK3739937 SD 800 mg Participants received single oral dose of 800 mg of GSK3739937 as suspension in Treatment Period 1. | 6 |
| Part 1 (Cohort 1) - SD PBO Participants received single oral dose of Placebo in Treatment Period 1. | 3 |
| Part 1 (Cohort 2) - SD PBO/ GSK3739937 SD 160 mg/ GSK3739937 SD 640 mg Participants received single oral dose of Placebo as suspension in Treatment Period 1, followed by single oral dose of 160 mg of GSK3739937 as suspension in Treatment Period 2, and followed by single oral dose of 640 mg of GSK3739937 as suspension Treatment in Period 3. | 5 |
| Part 1 (Cohort 2) - GSK3739937 SD 30mg/ SD PBO/ GSK3739937 SD 640mg Participants received single oral dose of 30 mg of GSK3739937 as suspension in Treatment Period 1, followed by single oral dose of Placebo as suspension in Treatment Period 2, and followed by single oral dose of 640 mg of GSK3739937 as suspension in Treatment Period 3. | 4 |
| Part 1 (Cohort 2) - GSK3739937 SD 30 mg/ GSK3739937 SD 160 mg/SD PBO Participants received single oral dose of 30 mg of GSK3739937 as suspension in Treatment Period 1, followed by single oral dose of 160 mg of GSK3739937 in Period 2, and followed by single oral dose of Placebo in Period 3. | 3 |
| Part 2 - Once Daily (QD) PBO Participants received once daily oral doses of Placebo as suspension for 14 days in Treatment Period 1. | 9 |
| Part 2 (Cohort 3) - GSK3739937 QD 25 mg Participants received once daily oral doses of 25 mg of GSK3739937 as suspension for 14 days in Treatment Period 1. | 7 |
| Part 2 (Cohort 4) - GSK3739937 QD 50 mg Participants received once daily oral doses of 50 mg of GSK3739937 as suspension for 14 days in Treatment Period 1. | 7 |
| Part 2 (Cohort 5) - GSK3739937 QD 100 mg Participants received once daily oral doses of 100 mg of GSK3739937 as suspension for 18 days in Treatment Period 1. | 7 |
| Part 2 - Once Weekly (QW) PBO Participants received once weekly oral doses of Placebo as suspension for over 3 weeks in Treatment Period 1. | 3 |
| Part 2 (Cohort 6) - GSK3739937 QW 500 mg Participants received once weekly oral doses of 500 mg of GSK3739937 as suspension for over 3 weeks in Treatment Period 1. | 7 |
| Part 3 (Cohort 7) - GSK3739937 PiB Fed/ GSK3739937 Tablet Fed/ GSK3739937 Tablet Fasted Participants received single dose of 100 mg of powder in bottle (PiB) as oral suspension under moderate fed conditions in Treatment Period 1, followed by single oral dose of 100 mg of GSK3739937 tablet under moderate fed conditions in Treatment Period 2 and followed by single dose of 100 mg of GSK3739937 tablet under fasted conditions in Treatment Period 3. | 5 |
| Part 3 (Cohort 7) - GSK3739937 Tablet Fed/ GSK3739937 Tablet Fasted/ GSK3739937 PiB Fed Participants received single oral dose of 100 mg of GSK3739937 tablet under moderate fed conditions in Treatment Period 1, followed by single oral dose of 100 mg GSK3739937 tablet under fasted conditions in Treatment Period 2 and followed by single dose of 100 mg PiB as oral suspension under moderate fed conditions in Treatment Period 3. | 6 |
| Part 3 (Cohort 7) - GSK3739937 Tablet Fasted/ GSK3739937 PiB Fed/ GSK3739937 Tablet Fed Participants received single oral dose of 100 mg of GSK3739937 tablet under fasted condition in Treatment Period 1, followed by single oral dose of 100 mg PiB as oral suspension under moderate fed conditions in Treatment Period 2 and followed by single oral dose of 100 mg GSK3739937 tablet under fed conditions in Treatment Period 3. | 6 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1:Treatment Period 1-Up to 9 Weeks | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1:Treatment Period 2-Up to 9 Weeks | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1:Treatment Period 2-Up to 9 Weeks | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1:Treatment Period 3-Up to 9 Weeks | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1:Treatment Period 3-Up to 9 Weeks | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2:Treatment Period 1-Up to 5 Weeks | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3:Treatment Period 1-Up to 4 Weeks | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 3:Treatment Period 2-Up to 4 Weeks | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1 (Cohort 1) - GSK3739937 SD 10 mg/ SD PBO/ GSK3739937 SD 320 mg | Part 1 (Cohort 1) - GSK3739937 SD 10 mg/ GSK3739937 SD 80 mg/SD PBO | Part 1 (Cohort 1) - GSK3739937 SD 800 mg | Part 1 (Cohort 1) - SD PBO | Part 1 (Cohort 2) - SD PBO/ GSK3739937 SD 160 mg/ GSK3739937 SD 640 mg | Part 1 (Cohort 2) - GSK3739937 SD 30mg/ SD PBO/ GSK3739937 SD 640mg | Part 1 (Cohort 2) - GSK3739937 SD 30 mg/ GSK3739937 SD 160 mg/SD PBO | Part 2 - Once Daily (QD) PBO | Part 2 (Cohort 3) - GSK3739937 QD 25 mg | Part 1 (Cohort 1) - Single Dose (SD) Placebo (PBO)/GSK3739937 SD 80 mg/GSK3739937 SD 320 mg | Part 2 (Cohort 4) - GSK3739937 QD 50 mg | Part 2 (Cohort 5) - GSK3739937 QD 100 mg | Part 2 - Once Weekly (QW) PBO | Part 2 (Cohort 6) - GSK3739937 QW 500 mg | Part 3 (Cohort 7) - GSK3739937 PiB Fed/ GSK3739937 Tablet Fed/ GSK3739937 Tablet Fasted | Part 3 (Cohort 7) - GSK3739937 Tablet Fed/ GSK3739937 Tablet Fasted/ GSK3739937 PiB Fed | Part 3 (Cohort 7) - GSK3739937 Tablet Fasted/ GSK3739937 PiB Fed/ GSK3739937 Tablet Fed | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized <=18 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 19-64 | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 9 Participants | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 3 Participants | 7 Participants | 5 Participants | 6 Participants | 6 Participants | 91 Participants |
| Age, Customized >=65 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 5 Participants | 5 Participants | 54 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 8 Participants | 7 Participants | 4 Participants | 7 Participants | 6 Participants | 3 Participants | 7 Participants | 5 Participants | 6 Participants | 6 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 3 | 0 / 7 | 0 / 15 | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 4 / 21 | 1 / 6 | 3 / 6 | 3 / 6 | 0 / 6 | 2 / 6 | 4 / 6 | 2 / 6 | 3 / 9 | 0 / 7 | 2 / 7 | 5 / 7 | 0 / 3 | 4 / 7 | 2 / 15 | 4 / 17 | 6 / 15 |
| serious Total, serious adverse events | 0 / 21 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 3 | 0 / 7 | 0 / 15 | 0 / 17 | 0 / 15 |
Outcome results
Primary
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 4.6 International units per Liter (IU/L) | Standard Deviation 6.06 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | 1.6 International units per Liter (IU/L) | Standard Deviation 7.78 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -1.5 International units per Liter (IU/L) | Standard Deviation 6.07 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -29.3 International units per Liter (IU/L) | Standard Deviation 140.65 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | 0.776 International units per Liter (IU/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | -1 International units per Liter (IU/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 5 International units per Liter (IU/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -8 International units per Liter (IU/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 8.3 International units per Liter (IU/L) | Standard Deviation 4.27 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -0.1978 International units per Liter (IU/L) | Standard Deviation 0.48809 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | -4.2 International units per Liter (IU/L) | Standard Deviation 6.05 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -4.5 International units per Liter (IU/L) | Standard Deviation 4.93 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 6.7 International units per Liter (IU/L) | Standard Deviation 3.72 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | -0.8 International units per Liter (IU/L) | Standard Deviation 3.49 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -2 International units per Liter (IU/L) | Standard Deviation 2.83 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -0.0777 International units per Liter (IU/L) | Standard Deviation 0.72185 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -0.1292 International units per Liter (IU/L) | Standard Deviation 0.91507 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -0.5 International units per Liter (IU/L) | Standard Deviation 4.04 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | 0.3 International units per Liter (IU/L) | Standard Deviation 9.35 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 3 International units per Liter (IU/L) | Standard Deviation 3.95 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | 0.2242 International units per Liter (IU/L) | Standard Deviation 0.3425 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -3.8 International units per Liter (IU/L) | Standard Deviation 4.26 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | -3.5 International units per Liter (IU/L) | Standard Deviation 6.32 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 6.2 International units per Liter (IU/L) | Standard Deviation 4.92 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -60.5 International units per Liter (IU/L) | Standard Deviation 132.53 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 8.8 International units per Liter (IU/L) | Standard Deviation 8.04 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -1.8 International units per Liter (IU/L) | Standard Deviation 4.79 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | 1.2 International units per Liter (IU/L) | Standard Deviation 10.19 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALT | -1.3 International units per Liter (IU/L) | Standard Deviation 3.39 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | AST | -1.5 International units per Liter (IU/L) | Standard Deviation 3.02 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | CPK | -20 International units per Liter (IU/L) | Standard Deviation 39.47 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) | ALP | 6.2 International units per Liter (IU/L) | Standard Deviation 2.14 |
Primary
Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -1.2 Units per liter (U/L) | Standard Deviation 17.38 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 7.8 Units per liter (U/L) | Standard Deviation 25.41 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 12 Units per liter (U/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -31 Units per liter (U/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -0.7 Units per liter (U/L) | Standard Deviation 6.12 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -15.5 Units per liter (U/L) | Standard Deviation 25.76 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -0.7 Units per liter (U/L) | Standard Deviation 4.46 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -8 Units per liter (U/L) | Standard Deviation 20.01 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 3.7 Units per liter (U/L) | Standard Deviation 4.76 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -1.3 Units per liter (U/L) | Standard Deviation 3.93 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 5.8 Units per liter (U/L) | Standard Deviation 12.02 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 3.7 Units per liter (U/L) | Standard Deviation 3.67 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 3.7 Units per liter (U/L) | Standard Deviation 4.27 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -1.7 Units per liter (U/L) | Standard Deviation 11.52 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 3.7 Units per liter (U/L) | Standard Deviation 17.24 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 3.8 Units per liter (U/L) | Standard Deviation 5.19 |
Primary
Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | -0.02 Millimoles per Liter (mmol/L) | Standard Deviation 0.303 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 1.8 Millimoles per Liter (mmol/L) | Standard Deviation 2.62 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | 0.1683 Millimoles per Liter (mmol/L) | Standard Deviation 0.46481 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.0693 Millimoles per Liter (mmol/L) | Standard Deviation 0.10417 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -1.6 Millimoles per Liter (mmol/L) | Standard Deviation 2.79 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.1294 Millimoles per Liter (mmol/L) | Standard Deviation 0.59228 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.0611 Millimoles per Liter (mmol/L) | Standard Deviation 0.13184 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | -0.2777 Millimoles per Liter (mmol/L) | Standard Deviation 0.7798 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 0 Millimoles per Liter (mmol/L) | Standard Deviation 1.64 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0.0046 Millimoles per Liter (mmol/L) | Standard Deviation 0.05426 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.29 Millimoles per Liter (mmol/L) | Standard Deviation 0.46027 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | -0.0027 Millimoles per Liter (mmol/L) | Standard Deviation 0.44009 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | -0.0187 Millimoles per Liter (mmol/L) | Standard Deviation 0.20182 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | -0.025 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 0 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | 0.18 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 2 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | 1.071 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | -0.2 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.104 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | 0.181 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -1 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | -0.078 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.097 Millimoles per Liter (mmol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.499 Millimoles per Liter (mmol/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | -0.2225 Millimoles per Liter (mmol/L) | Standard Deviation 0.43845 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 1.8 Millimoles per Liter (mmol/L) | Standard Deviation 2.48 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.0377 Millimoles per Liter (mmol/L) | Standard Deviation 0.1266 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | -0.2627 Millimoles per Liter (mmol/L) | Standard Deviation 0.52795 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.3147 Millimoles per Liter (mmol/L) | Standard Deviation 0.22689 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.75 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.0208 Millimoles per Liter (mmol/L) | Standard Deviation 0.10249 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | -0.069 Millimoles per Liter (mmol/L) | Standard Deviation 0.20186 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | -0.4165 Millimoles per Liter (mmol/L) | Standard Deviation 0.79561 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | 0.18 Millimoles per Liter (mmol/L) | Standard Deviation 0.354 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | -0.0605 Millimoles per Liter (mmol/L) | Standard Deviation 0.51701 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 1 Millimoles per Liter (mmol/L) | Standard Deviation 1.26 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | -0.0137 Millimoles per Liter (mmol/L) | Standard Deviation 0.06173 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0.0068 Millimoles per Liter (mmol/L) | Standard Deviation 0.03086 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | 0.1247 Millimoles per Liter (mmol/L) | Standard Deviation 0.15293 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | 0.2975 Millimoles per Liter (mmol/L) | Standard Deviation 0.7629 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -5 Millimoles per Liter (mmol/L) | Standard Deviation 1.41 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.444 Millimoles per Liter (mmol/L) | Standard Deviation 0.16643 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | 0.5217 Millimoles per Liter (mmol/L) | Standard Deviation 0.21608 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 3.3 Millimoles per Liter (mmol/L) | Standard Deviation 3.5 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.1387 Millimoles per Liter (mmol/L) | Standard Deviation 0.36972 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 0.2 Millimoles per Liter (mmol/L) | Standard Deviation 0.98 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.124 Millimoles per Liter (mmol/L) | Standard Deviation 0.13169 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | 0.18 Millimoles per Liter (mmol/L) | Standard Deviation 0.293 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.1453 Millimoles per Liter (mmol/L) | Standard Deviation 0.04816 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | 0.0318 Millimoles per Liter (mmol/L) | Standard Deviation 0.41469 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | -0.2337 Millimoles per Liter (mmol/L) | Standard Deviation 0.3573 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.0707 Millimoles per Liter (mmol/L) | Standard Deviation 0.13915 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | -0.224 Millimoles per Liter (mmol/L) | Standard Deviation 0.87169 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | 1.7 Millimoles per Liter (mmol/L) | Standard Deviation 1.51 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | -0.086 Millimoles per Liter (mmol/L) | Standard Deviation 0.13432 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | 0.1 Millimoles per Liter (mmol/L) | Standard Deviation 0.261 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | -0.5298 Millimoles per Liter (mmol/L) | Standard Deviation 0.52526 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | -0.0478 Millimoles per Liter (mmol/L) | Standard Deviation 0.03086 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | -0.0108 Millimoles per Liter (mmol/L) | Standard Deviation 0.16164 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 1 Millimoles per Liter (mmol/L) | Standard Deviation 1.26 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | -0.119 Millimoles per Liter (mmol/L) | Standard Deviation 0.62517 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.157 Millimoles per Liter (mmol/L) | Standard Deviation 0.22077 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 1.7 Millimoles per Liter (mmol/L) | Standard Deviation 1.97 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -1.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.51 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | -0.2 Millimoles per Liter (mmol/L) | Standard Deviation 2.14 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.379 Millimoles per Liter (mmol/L) | Standard Deviation 0.22041 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.0047 Millimoles per Liter (mmol/L) | Standard Deviation 0.5061 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | -0.28 Millimoles per Liter (mmol/L) | Standard Deviation 0.24 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.0208 Millimoles per Liter (mmol/L) | Standard Deviation 0.10888 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.0052 Millimoles per Liter (mmol/L) | Standard Deviation 0.08782 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | -0.0863 Millimoles per Liter (mmol/L) | Standard Deviation 0.32709 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | -0.7 Millimoles per Liter (mmol/L) | Standard Deviation 1.51 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | 0.082 Millimoles per Liter (mmol/L) | Standard Deviation 0.11534 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0.0752 Millimoles per Liter (mmol/L) | Standard Deviation 0.06035 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | 0.2975 Millimoles per Liter (mmol/L) | Standard Deviation 0.47451 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | 0.004 Millimoles per Liter (mmol/L) | Standard Deviation 0.35306 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 0.7 Millimoles per Liter (mmol/L) | Standard Deviation 2.25 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.1898 Millimoles per Liter (mmol/L) | Standard Deviation 0.3552 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | 0.087 Millimoles per Liter (mmol/L) | Standard Deviation 0.12521 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | -0.8 Millimoles per Liter (mmol/L) | Standard Deviation 1.83 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.1848 Millimoles per Liter (mmol/L) | Standard Deviation 0.25449 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | -0.07 Millimoles per Liter (mmol/L) | Standard Deviation 0.234 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | -0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.37 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | -0.0388 Millimoles per Liter (mmol/L) | Standard Deviation 0.30208 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | -0.2975 Millimoles per Liter (mmol/L) | Standard Deviation 0.72872 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.2203 Millimoles per Liter (mmol/L) | Standard Deviation 0.17728 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | 0.2023 Millimoles per Liter (mmol/L) | Standard Deviation 0.22274 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | 0.043 Millimoles per Liter (mmol/L) | Standard Deviation 0.12387 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0.0342 Millimoles per Liter (mmol/L) | Standard Deviation 0.03086 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Phosphate | -0.0108 Millimoles per Liter (mmol/L) | Standard Deviation 0.05669 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | LDL | -0.0388 Millimoles per Liter (mmol/L) | Standard Deviation 0.29351 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Sodium | 2.2 Millimoles per Liter (mmol/L) | Standard Deviation 0.98 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Potassium | -0.12 Millimoles per Liter (mmol/L) | Standard Deviation 0.214 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Bicarbonate | 1.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.51 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Triglycerides | 0.1467 Millimoles per Liter (mmol/L) | Standard Deviation 0.25766 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | HDL | -0.043 Millimoles per Liter (mmol/L) | Standard Deviation 0.07956 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Chloride | 0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.03 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | BUN | -0.595 Millimoles per Liter (mmol/L) | Standard Deviation 0.29149 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Cholesterol | 0.142 Millimoles per Liter (mmol/L) | Standard Deviation 0.09784 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Glucose | -0.3147 Millimoles per Liter (mmol/L) | Standard Deviation 0.25488 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Calcium | 0.0375 Millimoles per Liter (mmol/L) | Standard Deviation 0.05646 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides | Magnesium | 0.0137 Millimoles per Liter (mmol/L) | Standard Deviation 0.02117 |
Primary
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.2839 Micromoles per Liter (umol/L) | Standard Deviation 1.10348 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 1.8171 Micromoles per Liter (umol/L) | Standard Deviation 5.38547 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -0.19 Micromoles per Liter (umol/L) | Standard Deviation 3.2598 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -8.84 Micromoles per Liter (umol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -1.71 Micromoles per Liter (umol/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0 Micromoles per Liter (umol/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 6.188 Micromoles per Liter (umol/L) | Standard Deviation 8.27379 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.1995 Micromoles per Liter (umol/L) | Standard Deviation 0.62518 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -0.855 Micromoles per Liter (umol/L) | Standard Deviation 2.8098 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.4895 Micromoles per Liter (umol/L) | Standard Deviation 0.46819 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.57 Micromoles per Liter (umol/L) | Standard Deviation 0.883 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 6.0407 Micromoles per Liter (umol/L) | Standard Deviation 3.93024 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.285 Micromoles per Liter (umol/L) | Standard Deviation 2.5171 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.285 Micromoles per Liter (umol/L) | Standard Deviation 1.28724 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 4.5673 Micromoles per Liter (umol/L) | Standard Deviation 8.82968 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.285 Micromoles per Liter (umol/L) | Standard Deviation 2.7396 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.2565 Micromoles per Liter (umol/L) | Standard Deviation 1.18349 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -0.442 Micromoles per Liter (umol/L) | Standard Deviation 3.65553 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -1.71 Micromoles per Liter (umol/L) | Standard Deviation 2.163 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.3705 Micromoles per Liter (umol/L) | Standard Deviation 0.86801 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 3.978 Micromoles per Liter (umol/L) | Standard Deviation 4.80135 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.855 Micromoles per Liter (umol/L) | Standard Deviation 1.43069 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -3.135 Micromoles per Liter (umol/L) | Standard Deviation 3.8109 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 3.536 Micromoles per Liter (umol/L) | Standard Deviation 2.56208 |
Primary
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 3.2 Grams per Liter (g/L) | Standard Deviation 3.07 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 2 Grams per Liter (g/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 4.5 Grams per Liter (g/L) | Standard Deviation 3.83 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 6.3 Grams per Liter (g/L) | Standard Deviation 3.33 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 1 Grams per Liter (g/L) | Standard Deviation 4.15 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 3.7 Grams per Liter (g/L) | Standard Deviation 2.88 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 4 Grams per Liter (g/L) | Standard Deviation 3.85 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 3.5 Grams per Liter (g/L) | Standard Deviation 1.97 |
Primary
Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0.09 Picogram (pg) | Standard Deviation 0.314 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.5 Picogram (pg) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0.33 Picogram (pg) | Standard Deviation 0.294 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.08 Picogram (pg) | Standard Deviation 0.387 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.13 Picogram (pg) | Standard Deviation 0.32 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.13 Picogram (pg) | Standard Deviation 0.528 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.02 Picogram (pg) | Standard Deviation 0.232 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.03 Picogram (pg) | Standard Deviation 0.103 |
Primary
Part 1 - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0083 Proportion of red blood cells in blood | Standard Deviation 0.01231 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.014 Proportion of red blood cells in blood | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.015 Proportion of red blood cells in blood | Standard Deviation 0.0304 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0237 Proportion of red blood cells in blood | Standard Deviation 0.01491 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0012 Proportion of red blood cells in blood | Standard Deviation 0.02409 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0047 Proportion of red blood cells in blood | Standard Deviation 0.00866 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0117 Proportion of red blood cells in blood | Standard Deviation 0.01862 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0175 Proportion of red blood cells in blood | Standard Deviation 0.01319 |
Primary
Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 2.8 Grams per liter (g/L) | Standard Deviation 4.44 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 2 Grams per liter (g/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 7.5 Grams per liter (g/L) | Standard Deviation 8.41 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 6.7 Grams per liter (g/L) | Standard Deviation 5.2 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 1 Grams per liter (g/L) | Standard Deviation 8.51 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 2.7 Grams per liter (g/L) | Standard Deviation 2.73 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 4.3 Grams per liter (g/L) | Standard Deviation 5.68 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 5.2 Grams per liter (g/L) | Standard Deviation 4.07 |
Primary
Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | 0.0008 Proportion of reticulocytes in blood | Standard Deviation 0.00363 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | 0.002 Proportion of reticulocytes in blood | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0045 Proportion of reticulocytes in blood | Standard Deviation 0.00622 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0008 Proportion of reticulocytes in blood | Standard Deviation 0.00264 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0007 Proportion of reticulocytes in blood | Standard Deviation 0.00234 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0015 Proportion of reticulocytes in blood | Standard Deviation 0.00302 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0008 Proportion of reticulocytes in blood | Standard Deviation 0.00194 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0008 Proportion of reticulocytes in blood | Standard Deviation 0.0016 |
Primary
Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 0.3 Giga cells per liter (10^9 cells/L) | Standard Deviation 26.73 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | -0.01 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.024 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.05 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.092 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.14 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.391 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.3 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.486 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.04 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.124 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.5 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.1 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 2 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.2 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.7 Giga cells per liter (10^9 cells/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.22 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.306 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.482 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.147 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.063 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 8.2 Giga cells per liter (10^9 cells/L) | Standard Deviation 25.59 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.08 Giga cells per liter (10^9 cells/L) | Standard Deviation 1.303 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.08 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.075 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.248 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.194 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 16 Giga cells per liter (10^9 cells/L) | Standard Deviation 27.71 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.03 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.468 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.075 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -6.3 Giga cells per liter (10^9 cells/L) | Standard Deviation 7.87 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | -0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.041 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.03 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.121 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.13 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.463 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.23 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.339 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.133 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.02 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.041 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.33 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.48 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 8.8 Giga cells per liter (10^9 cells/L) | Standard Deviation 20.5 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.11 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.22 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.117 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.25 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.084 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 13.2 Giga cells per liter (10^9 cells/L) | Standard Deviation 19.05 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.08 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.223 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.08 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.117 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.22 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.248 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 0.2 Giga cells per liter (10^9 cells/L) | Standard Deviation 13 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.03 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.7 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 Giga cells per liter (10^9 cells/L) | Standard Deviation 0 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.07 Giga cells per liter (10^9 cells/L) | Standard Deviation 0.082 |
Primary
Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.079 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.1441 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.17 Trillion cells per liter (10^12 cells/L) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.197 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.3088 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.245 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.1623 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.048 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.2548 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.11 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.1368 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.157 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.1833 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.182 Trillion cells per liter (10^12 cells/L) | Standard Deviation 0.1526 |
Primary
Part 1 - Change From Baseline in Vital Signs - Body Temperature
Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Vital Signs - Body Temperature | -0.06 Degrees Celsius | Standard Deviation 0.32 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | -0.10 Degrees Celsius | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | 0.12 Degrees Celsius | Standard Deviation 0.248 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | -0.05 Degrees Celsius | Standard Deviation 0.226 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | 0.10 Degrees Celsius | Standard Deviation 0.19 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | 0.02 Degrees Celsius | Standard Deviation 0.117 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | 0.08 Degrees Celsius | Standard Deviation 0.286 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Vital Signs - Body Temperature | 0.20 Degrees Celsius | Standard Deviation 0.155 |
Primary
Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 5.3 Millimeters of mercury (mmHg) | Standard Deviation 7.82 |
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 4.0 Millimeters of mercury (mmHg) | Standard Deviation 4.36 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0.5 Millimeters of mercury (mmHg) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1.8 Millimeters of mercury (mmHg) | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -0.1 Millimeters of mercury (mmHg) | Standard Deviation 14.68 |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 3.0 Millimeters of mercury (mmHg) | Standard Deviation 8.2 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 4.6 Millimeters of mercury (mmHg) | Standard Deviation 7.07 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 3.7 Millimeters of mercury (mmHg) | Standard Deviation 9.57 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 7.3 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1.7 Millimeters of mercury (mmHg) | Standard Deviation 6.15 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 8.04 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -1.2 Millimeters of mercury (mmHg) | Standard Deviation 4.05 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 8.13 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 2.4 Millimeters of mercury (mmHg) | Standard Deviation 6.34 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 5.5 Millimeters of mercury (mmHg) | Standard Deviation 8.95 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 4.7 Millimeters of mercury (mmHg) | Standard Deviation 7.06 |
Primary
Part 1 - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 1.5 Beats per minute | Standard Deviation 5.03 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 15.7 Beats per minute | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 3.5 Beats per minute | Standard Deviation 7.4 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | -0.2 Beats per minute | Standard Deviation 3.45 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 5.9 Beats per minute | Standard Deviation 2.64 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 4.8 Beats per minute | Standard Deviation 5.74 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | -0.9 Beats per minute | Standard Deviation 7.98 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Vital Signs - Pulse Rate | 0.0 Beats per minute | Standard Deviation 9.71 |
Primary
Part 1 - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 0.7 Breaths per minute | Standard Deviation 2.97 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | -5.0 Breaths per minute | — |
| GSK3739937 SD 30 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | -3.0 Breaths per minute | Standard Deviation 1.41 |
| GSK3739937 SD 80 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 3.7 Breaths per minute | Standard Deviation 1.03 |
| GSK3739937 SD 160 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 0.7 Breaths per minute | Standard Deviation 2.07 |
| GSK3739937 SD 320 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 0.3 Breaths per minute | Standard Deviation 1.51 |
| GSK3739937 SD 640 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 0.3 Breaths per minute | Standard Deviation 1.51 |
| GSK3739937 SD 800 mg | Part 1 - Change From Baseline in Vital Signs - Respiratory Rate | 0.7 Breaths per minute | Standard Deviation 3.27 |
Primary
Part 1 - Number of 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 intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/Standard of care (SOC) to prevent one of the other outcomes mentioned before.
Time frame: Up to 27 weeks
Population: Safety Population included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 7 Events |
| Placebo (PBO) Single Dose | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 30 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Events |
| GSK3739937 SD 30 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 80 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Events |
| GSK3739937 SD 80 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 160 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 Events |
| GSK3739937 SD 160 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 320 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Events |
| GSK3739937 SD 320 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 640 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
| GSK3739937 SD 640 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Events |
| GSK3739937 SD 800 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Events |
| GSK3739937 SD 800 mg | Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Events |
Primary
Part 1 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Time frame: Up to 27 weeks
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 4 Participants |
| Placebo (PBO) Single Dose | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
| GSK3739937 SD 30 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 30 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
| GSK3739937 SD 80 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 80 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
| GSK3739937 SD 160 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 2 Participants |
| GSK3739937 SD 160 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 0 Participants |
| GSK3739937 SD 320 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 3 Participants |
| GSK3739937 SD 320 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
| GSK3739937 SD 640 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 0 Participants |
| GSK3739937 SD 640 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 800 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 2 Participants |
| GSK3739937 SD 800 mg | Part 1 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
Primary
Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Time frame: Up to 27 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 1 Participants |
| Placebo (PBO) Single Dose | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| Placebo (PBO) Single Dose | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 20 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 4 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 2 Participants |
| GSK3739937 SD 30 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 30 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 0 Participants |
| GSK3739937 SD 30 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 6 Participants |
| GSK3739937 SD 80 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 0 Participants |
| GSK3739937 SD 80 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 6 Participants |
| GSK3739937 SD 80 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 160 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 6 Participants |
| GSK3739937 SD 160 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 0 Participants |
| GSK3739937 SD 160 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 320 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 5 Participants |
| GSK3739937 SD 320 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 1 Participants |
| GSK3739937 SD 320 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 640 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 6 Participants |
| GSK3739937 SD 640 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 0 Participants |
| GSK3739937 SD 640 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 800 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Normal | 0 Participants |
| GSK3739937 SD 800 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Not Clinically Significant | 6 Participants |
| GSK3739937 SD 800 mg | Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings | Abnormal - Clinically Significant | 0 Participants |
Primary
Part 2 - Number of Any AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: 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 important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Time frame: Up to 5 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Number of Any AEs and SAEs | AEs | 3 Events |
| Placebo (PBO) Single Dose | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Any AEs and SAEs | AEs | 0 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 SD 30 mg | Part 2 - Number of Any AEs and SAEs | AEs | 2 Events |
| GSK3739937 SD 30 mg | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 SD 80 mg | Part 2 - Number of Any AEs and SAEs | AEs | 5 Events |
| GSK3739937 SD 80 mg | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 SD 160 mg | Part 2 - Number of Any AEs and SAEs | AEs | 0 Events |
| GSK3739937 SD 160 mg | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 SD 320 mg | Part 2 - Number of Any AEs and SAEs | AEs | 4 Events |
| GSK3739937 SD 320 mg | Part 2 - Number of Any AEs and SAEs | SAEs | 0 Events |
Primary
Part 2 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Time frame: Up to 5 weeks
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
| Placebo (PBO) Single Dose | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 2 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 30 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
| GSK3739937 SD 30 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 3 Participants |
| GSK3739937 SD 80 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 0 Participants |
| GSK3739937 SD 80 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 0 Participants |
| GSK3739937 SD 160 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 160 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
| GSK3739937 SD 320 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 1 Participants |
| GSK3739937 SD 320 mg | Part 2 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 3 Participants |
Primary
Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Time frame: Up to 5 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 9 Participants |
| Placebo (PBO) Single Dose | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| Placebo (PBO) Single Dose | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 7 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 30 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 7 Participants |
| GSK3739937 SD 30 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| GSK3739937 SD 30 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 80 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 7 Participants |
| GSK3739937 SD 80 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| GSK3739937 SD 80 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 160 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 3 Participants |
| GSK3739937 SD 160 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| GSK3739937 SD 160 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 320 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 0 Participants |
| GSK3739937 SD 320 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 320 mg | Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 7 Participants |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALT | -3.1 International units per Liter (IU/L) | Standard Deviation 6.9 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | CPK | -1 International units per Liter (IU/L) | Standard Deviation 26.43 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | AST | -4.6 International units per Liter (IU/L) | Standard Deviation 5.2 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALP | -0.4 International units per Liter (IU/L) | Standard Deviation 14.44 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALP | -4.6 International units per Liter (IU/L) | Standard Deviation 10.61 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALT | -5.9 International units per Liter (IU/L) | Standard Deviation 5.84 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | AST | -7.1 International units per Liter (IU/L) | Standard Deviation 5.52 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALP | 5.9 International units per Liter (IU/L) | Standard Deviation 5.34 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | CPK | 19.4 International units per Liter (IU/L) | Standard Deviation 88.5 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | AST | -4.1 International units per Liter (IU/L) | Standard Deviation 4.53 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALT | -3.9 International units per Liter (IU/L) | Standard Deviation 7.1 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | CPK | 14.8 International units per Liter (IU/L) | Standard Deviation 41.63 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALP | 3.0 International units per Liter (IU/L) | Standard Deviation 9.76 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | ALT | 0.3 International units per Liter (IU/L) | Standard Deviation 4.27 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK | AST | 3.2 International units per Liter (IU/L) | Standard Deviation 3.25 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 3.7 Units per liter (U/L) | Standard Deviation 27.96 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 3.8 Units per liter (U/L) | Standard Deviation 22.06 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -6.3 Units per liter (U/L) | Standard Deviation 8.62 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -18.3 Units per liter (U/L) | Standard Deviation 17.85 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 0.3 Units per liter (U/L) | Standard Deviation 5.5 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 1.1 Units per liter (U/L) | Standard Deviation 2.54 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 7.2 Units per liter (U/L) | Standard Deviation 15.3 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 1.2 Units per liter (U/L) | Standard Deviation 2.48 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | -0.09 Millimoles per Liter (mmol/L) | Standard Deviation 0.44 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | -0.0573 Millimoles per Liter (mmol/L) | Standard Deviation 0.12367 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.2902 Millimoles per Liter (mmol/L) | Standard Deviation 0.38135 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | -0.2773 Millimoles per Liter (mmol/L) | Standard Deviation 0.58989 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | -0.0547 Millimoles per Liter (mmol/L) | Standard Deviation 0.09168 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | -0.0306 Millimoles per Liter (mmol/L) | Standard Deviation 0.14997 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | 0.0403 Millimoles per Liter (mmol/L) | Standard Deviation 0.20877 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | -0.2701 Millimoles per Liter (mmol/L) | Standard Deviation 0.56002 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | 0.3 Millimoles per Liter (mmol/L) | Standard Deviation 2.5 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | 0.0397 Millimoles per Liter (mmol/L) | Standard Deviation 0.9849 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | 0.6 Millimoles per Liter (mmol/L) | Standard Deviation 1.67 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.1438 Millimoles per Liter (mmol/L) | Standard Deviation 0.15951 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -1 Millimoles per Liter (mmol/L) | Standard Deviation 1.94 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | 3 Millimoles per Liter (mmol/L) | Standard Deviation 1.15 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | -0.29 Millimoles per Liter (mmol/L) | Standard Deviation 0.261 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -1.4 Millimoles per Liter (mmol/L) | Standard Deviation 1.4 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | -0.1477 Millimoles per Liter (mmol/L) | Standard Deviation 0.10973 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | -0.6503 Millimoles per Liter (mmol/L) | Standard Deviation 0.68612 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.5244 Millimoles per Liter (mmol/L) | Standard Deviation 0.48959 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | 0.408 Millimoles per Liter (mmol/L) | Standard Deviation 0.90851 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | -0.0996 Millimoles per Liter (mmol/L) | Standard Deviation 0.06635 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | 1.3 Millimoles per Liter (mmol/L) | Standard Deviation 0.76 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | -0.1614 Millimoles per Liter (mmol/L) | Standard Deviation 0.26907 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.1849 Millimoles per Liter (mmol/L) | Standard Deviation 0.13459 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | -0.2136 Millimoles per Liter (mmol/L) | Standard Deviation 0.12771 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | -0.6027 Millimoles per Liter (mmol/L) | Standard Deviation 0.19341 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.2807 Millimoles per Liter (mmol/L) | Standard Deviation 0.30973 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | 0.0319 Millimoles per Liter (mmol/L) | Standard Deviation 0.3552 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -0.6 Millimoles per Liter (mmol/L) | Standard Deviation 2.44 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | -0.0286 Millimoles per Liter (mmol/L) | Standard Deviation 0.08469 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | -0.2843 Millimoles per Liter (mmol/L) | Standard Deviation 0.42535 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | -1.0 Millimoles per Liter (mmol/L) | Standard Deviation 1.63 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.0777 Millimoles per Liter (mmol/L) | Standard Deviation 0.14711 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | 0 Millimoles per Liter (mmol/L) | Standard Deviation 0.191 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | -0.1020 Millimoles per Liter (mmol/L) | Standard Deviation 1.02466 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | -0.0527 Millimoles per Liter (mmol/L) | Standard Deviation 0.05659 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | 0.0831 Millimoles per Liter (mmol/L) | Standard Deviation 0.11469 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | -0.9 Millimoles per Liter (mmol/L) | Standard Deviation 1.07 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | 0.0434 Millimoles per Liter (mmol/L) | Standard Deviation 0.20744 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.0948 Millimoles per Liter (mmol/L) | Standard Deviation 0.21847 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | 0.2577 Millimoles per Liter (mmol/L) | Standard Deviation 0.33429 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | 0.0485 Millimoles per Liter (mmol/L) | Standard Deviation 0.09964 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | -1.3 Millimoles per Liter (mmol/L) | Standard Deviation 2.16 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | 0.3708 Millimoles per Liter (mmol/L) | Standard Deviation 0.43447 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | -0.3978 Millimoles per Liter (mmol/L) | Standard Deviation 0.24715 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | 0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.97 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | 0.0373 Millimoles per Liter (mmol/L) | Standard Deviation 0.07016 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -0.3 Millimoles per Liter (mmol/L) | Standard Deviation 2.07 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.0903 Millimoles per Liter (mmol/L) | Standard Deviation 0.86478 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | 0.1190 Millimoles per Liter (mmol/L) | Standard Deviation 0.53748 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | -0.0205 Millimoles per Liter (mmol/L) | Standard Deviation 0.06737 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | -0.22 Millimoles per Liter (mmol/L) | Standard Deviation 0.449 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.6058 Micromoles per Liter (umol/L) | Standard Deviation 1.12324 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 3.536 Micromoles per Liter (umol/L) | Standard Deviation 7.48795 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.19 Micromoles per Liter (umol/L) | Standard Deviation 3.9593 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.5863 Micromoles per Liter (umol/L) | Standard Deviation 1.10758 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -1.768 Micromoles per Liter (umol/L) | Standard Deviation 5.35289 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.244 Micromoles per Liter (umol/L) | Standard Deviation 3.6178 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -0.977 Micromoles per Liter (umol/L) | Standard Deviation 2.7674 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | -0.8061 Micromoles per Liter (umol/L) | Standard Deviation 0.95062 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -0.6314 Micromoles per Liter (umol/L) | Standard Deviation 4.5568 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.2817 Micromoles per Liter (umol/L) | Standard Deviation 1.28814 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 8.3980 Micromoles per Liter (umol/L) | Standard Deviation 2.89164 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 1.425 Micromoles per Liter (umol/L) | Standard Deviation 3.8109 |
Primary
Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | -3.7 Grams per Liter (g/L) | Standard Deviation 3.84 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | -7.1 Grams per Liter (g/L) | Standard Deviation 6.26 |
| GSK3739937 SD 30 mg | Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | -5.4 Grams per Liter (g/L) | Standard Deviation 3.91 |
| GSK3739937 SD 80 mg | Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 2.0 Grams per Liter (g/L) | Standard Deviation 2.83 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0.02 Picogram (pg) | Standard Deviation 0.63 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.3 Picogram (pg) | Standard Deviation 0.44 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0.16 Picogram (pg) | Standard Deviation 0.172 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.08 Picogram (pg) | Standard Deviation 0.605 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit | -0.0081 Proportion of red blood cells in blood | Standard Deviation 0.01342 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit | 0.0066 Proportion of red blood cells in blood | Standard Deviation 0.01838 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit | -0.0217 Proportion of red blood cells in blood | Standard Deviation 0.01963 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit | 0.0043 Proportion of red blood cells in blood | Standard Deviation 0.01929 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | -1.6 Grams per liter (g/L) | Standard Deviation 5.13 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | -1 Grams per liter (g/L) | Standard Deviation 7.21 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | -5.7 Grams per liter (g/L) | Standard Deviation 6.7 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 0.5 Grams per liter (g/L) | Standard Deviation 7.74 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0017 Proportion of reticulocytes in blood | Standard Deviation 0.0024 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0011 Proportion of reticulocytes in blood | Standard Deviation 0.00219 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes | 0.0010 Proportion of reticulocytes in blood | Standard Deviation 0.00306 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0012 Proportion of reticulocytes in blood | Standard Deviation 0.00264 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.03 10^9 cells/L | Standard Deviation 0.05 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.13 10^9 cells/L | Standard Deviation 0.26 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.02 10^9 cells/L | Standard Deviation 0.139 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.47 10^9 cells/L | Standard Deviation 0.784 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -11.9 10^9 cells/L | Standard Deviation 16.24 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -3.4 10^9 cells/L | Standard Deviation 18.12 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.04 10^9 cells/L | Standard Deviation 0.113 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.07 10^9 cells/L | Standard Deviation 0.281 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.03 10^9 cells/L | Standard Deviation 0.095 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.19 10^9 cells/L | Standard Deviation 0.682 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.01 10^9 cells/L | Standard Deviation 0.09 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.03 10^9 cells/L | Standard Deviation 0.427 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.01 10^9 cells/L | Standard Deviation 0.135 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -9.7 10^9 cells/L | Standard Deviation 20.11 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.03 10^9 cells/L | Standard Deviation 0.496 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0.03 10^9 cells/L | Standard Deviation 0.049 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.18 10^9 cells/L | Standard Deviation 0.877 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -15.5 10^9 cells/L | Standard Deviation 32.93 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.02 10^9 cells/L | Standard Deviation 0.075 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.02 10^9 cells/L | Standard Deviation 0.117 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | -0.02 10^9 cells/L | Standard Deviation 0.041 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.15 10^9 cells/L | Standard Deviation 0.274 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count | -0.06 10^12 cells/L | Standard Deviation 0.1592 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.017 10^12 cells/L | Standard Deviation 0.175 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count | -0.227 10^12 cells/L | Standard Deviation 0.2423 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.037 10^12 cells/L | Standard Deviation 0.2601 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature | 0.16 Degrees Celsius | Standard Deviation 0.283 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature | -0.07 Degrees Celsius | Standard Deviation 0.17 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature | 0.09 Degrees Celsius | Standard Deviation 0.135 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature | -0.08 Degrees Celsius | Standard Deviation 0.204 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -6.0 Millimeters of mercury (mmHg) | Standard Deviation 15.26 |
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -3.4 Millimeters of mercury (mmHg) | Standard Deviation 8.73 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0.8 Millimeters of mercury (mmHg) | Standard Deviation 7.21 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -2.1 Millimeters of mercury (mmHg) | Standard Deviation 11.58 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -2.1 Millimeters of mercury (mmHg) | Standard Deviation 5.57 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 5.45 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 4.08 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 6.17 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate | 1.1 Beats per minute | Standard Deviation 4.59 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate | -2.8 Beats per minute | Standard Deviation 4.98 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate | 5.0 Beats per minute | Standard Deviation 5.49 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate | 3.0 Beats per minute | Standard Deviation 4.75 |
Primary
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 14
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate | -0.4 Breaths per minute | Standard Deviation 2.19 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate | -3.4 Breaths per minute | Standard Deviation 1.51 |
| GSK3739937 SD 30 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate | 0.0 Breaths per minute | Standard Deviation 1.63 |
| GSK3739937 SD 80 mg | Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate | 1.2 Breaths per minute | Standard Deviation 3.13 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | ALP | 0.0 International units per Liter (IU/L) | Standard Deviation 2.65 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | ALT | -2.3 International units per Liter (IU/L) | Standard Deviation 7.77 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | AST | -3.0 International units per Liter (IU/L) | Standard Deviation 2.65 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | CPK | -18.7 International units per Liter (IU/L) | Standard Deviation 14.84 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | CPK | -22.6 International units per Liter (IU/L) | Standard Deviation 35.72 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | ALP | 1.9 International units per Liter (IU/L) | Standard Deviation 4.02 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | AST | -3 International units per Liter (IU/L) | Standard Deviation 1.83 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK | ALT | -3.1 International units per Liter (IU/L) | Standard Deviation 2.91 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 2.7 Units per liter (U/L) | Standard Deviation 7.51 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -2.0 Units per liter (U/L) | Standard Deviation 5.57 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | -10 Units per liter (U/L) | Standard Deviation 22.5 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -1.9 Units per liter (U/L) | Standard Deviation 4.67 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | -0.0913 Millimoles per Liter (mmol/L) | Standard Deviation 0.1416 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.4137 Millimoles per Liter (mmol/L) | Standard Deviation 0.34187 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | 1.3 Millimoles per Liter (mmol/L) | Standard Deviation 0.58 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | 0.0137 Millimoles per Liter (mmol/L) | Standard Deviation 0.02367 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -0.7 Millimoles per Liter (mmol/L) | Standard Deviation 2.08 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | 0.0540 Millimoles per Liter (mmol/L) | Standard Deviation 0.10437 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.1037 Millimoles per Liter (mmol/L) | Standard Deviation 0.1186 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | -0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.15 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | -0.4483 Millimoles per Liter (mmol/L) | Standard Deviation 0.39167 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | 0.0267 Millimoles per Liter (mmol/L) | Standard Deviation 0.07243 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | -0.10 Millimoles per Liter (mmol/L) | Standard Deviation 0.346 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | 0.1190 Millimoles per Liter (mmol/L) | Standard Deviation 0.54533 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | -0.2590 Millimoles per Liter (mmol/L) | Standard Deviation 0.23106 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | BUN | 0.408 Millimoles per Liter (mmol/L) | Standard Deviation 0.32121 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Glucose | -0.3014 Millimoles per Liter (mmol/L) | Standard Deviation 0.14978 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Bicarbonate | -0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.38 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Calcium | -0.0391 Millimoles per Liter (mmol/L) | Standard Deviation 0.10029 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Cholesterol | -0.203 Millimoles per Liter (mmol/L) | Standard Deviation 0.56917 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Chloride | 0.4 Millimoles per Liter (mmol/L) | Standard Deviation 1.62 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | HDL | -0.0703 Millimoles per Liter (mmol/L) | Standard Deviation 0.14776 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Potassium | -0.21 Millimoles per Liter (mmol/L) | Standard Deviation 0.418 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | LDL | -0.1107 Millimoles per Liter (mmol/L) | Standard Deviation 0.36147 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Magnesium | 0.0059 Millimoles per Liter (mmol/L) | Standard Deviation 0.04981 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Phosphate | 0.0464 Millimoles per Liter (mmol/L) | Standard Deviation 0.08088 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Sodium | -0.7 Millimoles per Liter (mmol/L) | Standard Deviation 1.5 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides | Triglycerides | 0.0129 Millimoles per Liter (mmol/L) | Standard Deviation 0.25175 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.5700 Micromoles per Liter (umol/L) | Standard Deviation 0.98727 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | -1.140 Micromoles per Liter (umol/L) | Standard Deviation 2.6121 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -1.1787 Micromoles per Liter (umol/L) | Standard Deviation 2.55189 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 1.4671 Micromoles per Liter (umol/L) | Standard Deviation 0.64254 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 1.71 Micromoles per Liter (umol/L) | Standard Deviation 1.71 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 2.2731 Micromoles per Liter (umol/L) | Standard Deviation 2.88068 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | -1.7 Grams per Liter (g/L) | Standard Deviation 5.03 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein | -2.1 Grams per Liter (g/L) | Standard Deviation 4.49 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.87 Picogram (pg) | Standard Deviation 0.666 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.83 Picogram (pg) | Standard Deviation 0.399 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit | -0.0120 Proportion of red blood cells in blood | Standard Deviation 0.02685 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit | -0.0094 Proportion of red blood cells in blood | Standard Deviation 0.00781 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | -5.7 Grams per liter (g/L) | Standard Deviation 7.64 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | -4.3 Grams per liter (g/L) | Standard Deviation 2.63 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes | 0.0003 Proportion of reticulocytes in blood | Standard Deviation 0.00379 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0001 Proportion of reticulocytes in blood | Standard Deviation 0.00227 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.03 10^9 cells/L | Standard Deviation 0.115 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.23 10^9 cells/L | Standard Deviation 0.115 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.07 10^9 cells/L | Standard Deviation 0.058 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.10 10^9 cells/L | Standard Deviation 0.173 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -21.3 10^9 cells/L | Standard Deviation 47.72 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.27 10^9 cells/L | Standard Deviation 0.315 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.06 10^9 cells/L | Standard Deviation 0.079 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.01 10^9 cells/L | Standard Deviation 0.069 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -9.3 10^9 cells/L | Standard Deviation 30.8 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.04 10^9 cells/L | Standard Deviation 0.378 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count | -0.060 10^12 cells/L | Standard Deviation 0.2787 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count | -0.014 10^12 cells/L | Standard Deviation 0.1021 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature | -0.07 Degrees Celsius | Standard Deviation 0.153 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature | -0.06 Degrees Celsius | Standard Deviation 0.113 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1.0 Millimeters of mercury (mmHg) | Standard Deviation 11.89 |
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 4.2 Millimeters of mercury (mmHg) | Standard Deviation 9.56 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1.5 Millimeters of mercury (mmHg) | Standard Deviation 5.42 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0.9 Millimeters of mercury (mmHg) | Standard Deviation 6.52 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate | 0.9 Beats per minute | Standard Deviation 1.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate | 5.2 Beats per minute | Standard Deviation 5.29 |
Primary
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 15
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate | 0.0 Breaths per minute | Standard Deviation 2 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate | -1.4 Breaths per minute | Standard Deviation 2.23 |
Primary
Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Population: Pharmacokinetic (PK) Population: The PK Population included all participants who undergo plasma or urine PK sampling and have evaluable PK assay results. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937 | 6455.362 Hour*nanogram/ millilitre (h*ng/mL) | Geometric Coefficient of Variation 25 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937 | 8646.757 Hour*nanogram/ millilitre (h*ng/mL) | Geometric Coefficient of Variation 33.9 |
| GSK3739937 SD 30 mg | Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937 | 3522.969 Hour*nanogram/ millilitre (h*ng/mL) | Geometric Coefficient of Variation 91 |
Comparison: The mixed model was used to estimate Food Effect for the log transformed parameter AUC (0-24). Analysis was performed using fed/ fasted state and tablet/ PiB as fixed effects and participant as a random effect.90% CI: [1.823, 3.323]Mixed Models Analysis
Comparison: The mixed model was used to estimate Tablet vs. PiB effect for the log transformed parameter AUC (0-24). Analysis was performed using the independent variables included a fixed effect for treatment (PiB or Tablet) and period, and participant as a random effect.90% CI: [1.223, 1.56]Mixed Models Analysis
Primary
Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 | 43323.02 h*ng/mL | Geometric Coefficient of Variation 27.3 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 | 58892.29 h*ng/mL | Geometric Coefficient of Variation 23.6 |
| GSK3739937 SD 30 mg | Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 | 27326.99 h*ng/mL | Geometric Coefficient of Variation 64 |
Comparison: The mixed model was used to estimate Food Effect for the log transformed parameter AUC (0-inf). Analysis was performed using fed/ fasted state and tablet/ PiB as fixed effects and participant as a random effect.90% CI: [1.629, 2.717]Mixed Models Analysis
Comparison: The mixed model was used to estimate Tablet vs. PiB effect for the log transformed parameter AUC (0-inf). Analysis was performed using the independent variables included a fixed effect for treatment (PiB or Tablet) and period, and participant as a random effect.90% CI: [1.22, 1.497]Mixed Models Analysis
Primary
Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALP | 5.9 International units per Liter (IU/L) | Standard Deviation 6.42 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALT | 1.3 International units per Liter (IU/L) | Standard Deviation 4.32 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | AST | 0.3 International units per Liter (IU/L) | Standard Deviation 3.67 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | CPK | -27.3 International units per Liter (IU/L) | Standard Deviation 52.49 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | CPK | -22.2 International units per Liter (IU/L) | Standard Deviation 45.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALP | 5.4 International units per Liter (IU/L) | Standard Deviation 5.91 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | AST | 0.4 International units per Liter (IU/L) | Standard Deviation 4.4 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALT | -0.2 International units per Liter (IU/L) | Standard Deviation 4.92 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | CPK | -62.1 International units per Liter (IU/L) | Standard Deviation 73.59 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALT | -0.4 International units per Liter (IU/L) | Standard Deviation 3.16 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | AST | -0.9 International units per Liter (IU/L) | Standard Deviation 3.02 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK | ALP | 5.2 International units per Liter (IU/L) | Standard Deviation 4.78 |
Primary
Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 0.5 Units per liter (U/L) | Standard Deviation 16.41 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 0.4 Units per liter (U/L) | Standard Deviation 18.92 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 1.2 Units per liter (U/L) | Standard Deviation 12.08 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | -0.6 Units per liter (U/L) | Standard Deviation 6.25 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Amylase | 5.1 Units per liter (U/L) | Standard Deviation 18.24 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase | Lipase | 2.7 Units per liter (U/L) | Standard Deviation 10.06 |
Primary
Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Triglycerides | 0.1558 Millimoles per Liter (mmol/L) | Standard Deviation 0.44508 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Magnesium | 0.0109 Millimoles per Liter (mmol/L) | Standard Deviation 0.07972 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | HDL | -0.0259 Millimoles per Liter (mmol/L) | Standard Deviation 0.13992 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Calcium | 0.055 Millimoles per Liter (mmol/L) | Standard Deviation 0.10971 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | LDL | 0.219 Millimoles per Liter (mmol/L) | Standard Deviation 0.42617 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Potassium | -0.03 Millimoles per Liter (mmol/L) | Standard Deviation 0.422 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Glucose | -0.2033 Millimoles per Liter (mmol/L) | Standard Deviation 0.39 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Bicarbonate | 1.5 Millimoles per Liter (mmol/L) | Standard Deviation 1.96 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Sodium | 0.5 Millimoles per Liter (mmol/L) | Standard Deviation 2.47 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Cholesterol | 0.1087 Millimoles per Liter (mmol/L) | Standard Deviation 0.30739 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | BUN | 0.6426 Millimoles per Liter (mmol/L) | Standard Deviation 0.91715 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Phosphate | -0.0021 Millimoles per Liter (mmol/L) | Standard Deviation 0.11269 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Chloride | -1.2 Millimoles per Liter (mmol/L) | Standard Deviation 2.57 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Potassium | -0.04 Millimoles per Liter (mmol/L) | Standard Deviation 0.361 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Glucose | -0.3755 Millimoles per Liter (mmol/L) | Standard Deviation 0.24961 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Bicarbonate | 0.4 Millimoles per Liter (mmol/L) | Standard Deviation 2.12 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Calcium | 0.0793 Millimoles per Liter (mmol/L) | Standard Deviation 0.10607 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Cholesterol | 0.1218 Millimoles per Liter (mmol/L) | Standard Deviation 0.3317 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Chloride | -2.2 Millimoles per Liter (mmol/L) | Standard Deviation 2.14 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | HDL | -0.0549 Millimoles per Liter (mmol/L) | Standard Deviation 0.12044 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | LDL | 0.2312 Millimoles per Liter (mmol/L) | Standard Deviation 0.46471 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Magnesium | 0.0217 Millimoles per Liter (mmol/L) | Standard Deviation 0.06338 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Phosphate | -0.0058 Millimoles per Liter (mmol/L) | Standard Deviation 0.07409 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Sodium | -1.1 Millimoles per Liter (mmol/L) | Standard Deviation 1.45 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Triglycerides | 0.1801 Millimoles per Liter (mmol/L) | Standard Deviation 0.37021 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | BUN | 0.504 Millimoles per Liter (mmol/L) | Standard Deviation 0.81856 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Magnesium | 0.0109 Millimoles per Liter (mmol/L) | Standard Deviation 0.0883 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Cholesterol | 0.0569 Millimoles per Liter (mmol/L) | Standard Deviation 0.47643 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Triglycerides | 0.0082 Millimoles per Liter (mmol/L) | Standard Deviation 0.30805 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Phosphate | -0.0021 Millimoles per Liter (mmol/L) | Standard Deviation 0.0965 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Calcium | 0.0666 Millimoles per Liter (mmol/L) | Standard Deviation 0.07293 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Glucose | -0.2145 Millimoles per Liter (mmol/L) | Standard Deviation 0.27017 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Sodium | 0.3 Millimoles per Liter (mmol/L) | Standard Deviation 1.95 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Potassium | -0.17 Millimoles per Liter (mmol/L) | Standard Deviation 0.364 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | HDL | -0.0415 Millimoles per Liter (mmol/L) | Standard Deviation 0.1084 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Bicarbonate | 1.5 Millimoles per Liter (mmol/L) | Standard Deviation 1.64 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | LDL | 0.0484 Millimoles per Liter (mmol/L) | Standard Deviation 0.55487 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | Chloride | -1.6 Millimoles per Liter (mmol/L) | Standard Deviation 1.92 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure | BUN | 0.4046 Millimoles per Liter (mmol/L) | Standard Deviation 1.00855 |
Primary
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.456 Micromoles per Liter (umol/L) | Standard Deviation 1.9886 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.3306 Micromoles per Liter (umol/L) | Standard Deviation 0.89198 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 3.0645 Micromoles per Liter (umol/L) | Standard Deviation 6.90318 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 0.905 Micromoles per Liter (umol/L) | Standard Deviation 3.7813 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.4124 Micromoles per Liter (umol/L) | Standard Deviation 1.068 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 1.716 Micromoles per Liter (umol/L) | Standard Deviation 6.168 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Direct Bilirubin | 0.2059 Micromoles per Liter (umol/L) | Standard Deviation 1.11784 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Creatinine | 2.9467 Micromoles per Liter (umol/L) | Standard Deviation 6.70465 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine | Total Bilirubin | 1.026 Micromoles per Liter (umol/L) | Standard Deviation 3.5282 |
Primary
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 5.1 Grams per Liter (g/L) | Standard Deviation 5.38 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 5.4 Grams per Liter (g/L) | Standard Deviation 4.87 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein | 4.5 Grams per Liter (g/L) | Standard Deviation 4.02 |
Primary
Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0 Picogram (pg) | Standard Deviation 0.433 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | -0.24 Picogram (pg) | Standard Deviation 0.487 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) | 0.05 Picogram (pg) | Standard Deviation 0.54 |
Primary
Part 3 - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0182 Proportion of red blood cells in blood | Standard Deviation 0.01826 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameter - Hematocrit | 0.013 Proportion of red blood cells in blood | Standard Deviation 0.02076 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameter - Hematocrit | 0.0159 Proportion of red blood cells in blood | Standard Deviation 0.01793 |
Primary
Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 6.7 Grams per liter (g/L) | Standard Deviation 5.87 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 4.5 Grams per liter (g/L) | Standard Deviation 7.07 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) | 5.7 Grams per liter (g/L) | Standard Deviation 5.37 |
Primary
Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0011 Proportion of reticulocytes in blood | Standard Deviation 0.00231 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0009 Proportion of reticulocytes in blood | Standard Deviation 0.00255 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes | -0.0012 Proportion of reticulocytes in blood | Standard Deviation 0.00224 |
Primary
Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0.01 10^9 cells/L | Standard Deviation 0.026 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.05 10^9 cells/L | Standard Deviation 0.052 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.11 10^9 cells/L | Standard Deviation 0.253 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.01 10^9 cells/L | Standard Deviation 0.099 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.16 10^9 cells/L | Standard Deviation 0.703 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 7 10^9 cells/L | Standard Deviation 15.83 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 1.5 10^9 cells/L | Standard Deviation 22.48 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.01 10^9 cells/L | Standard Deviation 0.132 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.15 10^9 cells/L | Standard Deviation 1.253 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.05 10^9 cells/L | Standard Deviation 0.087 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.08 10^9 cells/L | Standard Deviation 0.407 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.05 10^9 cells/L | Standard Deviation 0.092 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.16 10^9 cells/L | Standard Deviation 0.184 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -6.7 10^9 cells/L | Standard Deviation 21.4 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.04 10^9 cells/L | Standard Deviation 0.083 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0 10^9 cells/L | Standard Deviation 0 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.17 10^9 cells/L | Standard Deviation 0.594 |
Primary
Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and Day 6
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.229 10^12 cells/L | Standard Deviation 0.2193 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.197 10^12 cells/L | Standard Deviation 0.2287 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count | 0.189 10^12 cells/L | Standard Deviation 0.2014 |
Primary
Part 3 - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Vital Signs - Body Temperature | 0.08 Degrees Celsius | Standard Deviation 0.231 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Vital Signs - Body Temperature | 0.06 Degrees Celsius | Standard Deviation 0.237 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Vital Signs - Body Temperature | 0.15 Degrees Celsius | Standard Deviation 0.233 |
Primary
Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 6.2 Millimeters of mercury (mmHg) | Standard Deviation 7.2 |
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 2.3 Millimeters of mercury (mmHg) | Standard Deviation 4.02 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 3.8 Millimeters of mercury (mmHg) | Standard Deviation 10.1 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 3.4 Millimeters of mercury (mmHg) | Standard Deviation 8.63 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 9.3 Millimeters of mercury (mmHg) | Standard Deviation 8.08 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 4.4 Millimeters of mercury (mmHg) | Standard Deviation 5.79 |
Primary
Part 3 - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Vital Signs - Pulse Rate | 6.2 Beats per minute | Standard Deviation 6.8 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Vital Signs - Pulse Rate | 7.4 Beats per minute | Standard Deviation 4.98 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Vital Signs - Pulse Rate | 6.6 Beats per minute | Standard Deviation 5.48 |
Primary
Part 3 - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Change From Baseline in Vital Signs - Respiratory Rate | 0.4 Breaths per minute | Standard Deviation 2.03 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Change From Baseline in Vital Signs - Respiratory Rate | -0.3 Breaths per minute | Standard Deviation 2.31 |
| GSK3739937 SD 30 mg | Part 3 - Change From Baseline in Vital Signs - Respiratory Rate | 1.2 Breaths per minute | Standard Deviation 2.24 |
Primary
Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937 | 389.81 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 23.4 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937 | 524.99 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 31.8 |
| GSK3739937 SD 30 mg | Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937 | 227.88 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 93.5 |
Comparison: The mixed model was used to estimate Food Effect for the log transformed parameter Cmax. Analysis was performed using fed/ fasted state and tablet/ PiB as fixed effects and participant as a random effect.90% CI: [1.668, 3.19]Mixed Models Analysis
Comparison: The mixed model was used to estimate Tablet vs. PiB effect for the log transformed parameter Cmax. Analysis was performed using the independent variables included a fixed effect for treatment (PiB or Tablet) and period, and participant as a random effect.90% CI: [1.19, 1.582]Mixed Models Analysis
Primary
Part 3 - Number of Any AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: 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 important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Time frame: Up to 16 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Number of Any AEs and SAEs | AEs | 2 Events |
| Placebo (PBO) Single Dose | Part 3 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Any AEs and SAEs | AEs | 4 Events |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Any AEs and SAEs | SAEs | 0 Events |
| GSK3739937 SD 30 mg | Part 3 - Number of Any AEs and SAEs | AEs | 6 Events |
| GSK3739937 SD 30 mg | Part 3 - Number of Any AEs and SAEs | SAEs | 0 Events |
Primary
Part 3 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Time frame: Up to 16 weeks
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| Placebo (PBO) Single Dose | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 4 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
| GSK3739937 SD 30 mg | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Occult Blood | 1 Participants |
| GSK3739937 SD 30 mg | Part 3 - Number of Participants With Abnormal Urinalysis Parameters | Protein | 2 Participants |
Primary
Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Time frame: Up to 16 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 14 Participants |
| Placebo (PBO) Single Dose | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 1 Participants |
| Placebo (PBO) Single Dose | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 16 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 1 Participants |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 30 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Normal | 1 Participants |
| GSK3739937 SD 30 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Clinically Significant | 0 Participants |
| GSK3739937 SD 30 mg | Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings | Abnormal - Not Clinically Significant | 14 Participants |
Secondary
Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | NA litre/ hour (L/h) | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 2.3459 litre/ hour (L/h) | Geometric Coefficient of Variation 32.4 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 1.9857 litre/ hour (L/h) | Geometric Coefficient of Variation 15.5 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 2.1282 litre/ hour (L/h) | Geometric Coefficient of Variation 13.6 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 2.9847 litre/ hour (L/h) | Geometric Coefficient of Variation 25.2 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 3.3542 litre/ hour (L/h) | Geometric Coefficient of Variation 81.6 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 | 2.6477 litre/ hour (L/h) | Geometric Coefficient of Variation 34.2 |
Secondary
Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | NA Hours | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 75.8706 Hours | Geometric Coefficient of Variation 7.4 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 79.0711 Hours | Geometric Coefficient of Variation 14.4 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 91.8314 Hours | Geometric Coefficient of Variation 13.6 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 96.7684 Hours | Geometric Coefficient of Variation 22.7 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 82.6113 Hours | Geometric Coefficient of Variation 9 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 | 67.4404 Hours | Geometric Coefficient of Variation 9.3 |
Secondary
Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 637.8486 h*ng/mL | Geometric Coefficient of Variation 38.8 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 1976.944 h*ng/mL | Geometric Coefficient of Variation 24.3 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 5027.183 h*ng/mL | Geometric Coefficient of Variation 27.4 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 9490.296 h*ng/mL | Geometric Coefficient of Variation 15.4 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 13743.02 h*ng/mL | Geometric Coefficient of Variation 23.6 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 23829.99 h*ng/mL | Geometric Coefficient of Variation 53.1 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 | 42129.36 h*ng/mL | Geometric Coefficient of Variation 18.1 |
Secondary
Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | NA h*ng/mL | — |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 12788.34 h*ng/mL | Geometric Coefficient of Variation 32.4 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 40287.05 h*ng/mL | Geometric Coefficient of Variation 15.5 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 75181.6 h*ng/mL | Geometric Coefficient of Variation 13.6 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 107211.7 h*ng/mL | Geometric Coefficient of Variation 25.2 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 190803.9 h*ng/mL | Geometric Coefficient of Variation 81.6 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 | 302147.5 h*ng/mL | Geometric Coefficient of Variation 34.2 |
Secondary
Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 2486.061 h*ng/mL | Geometric Coefficient of Variation 46.4 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 11441.28 h*ng/mL | Geometric Coefficient of Variation 31.5 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 33650.11 h*ng/mL | Geometric Coefficient of Variation 42.5 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 64937.76 h*ng/mL | Geometric Coefficient of Variation 18.4 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 90730.34 h*ng/mL | Geometric Coefficient of Variation 25.9 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 158068.4 h*ng/mL | Geometric Coefficient of Variation 70 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 | 293636.9 h*ng/mL | Geometric Coefficient of Variation 33.6 |
Secondary
Part 1 (Cohort 1 and 2) - Cmax of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 39.22 ng/mL | Geometric Coefficient of Variation 41.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 127.3 ng/mL | Geometric Coefficient of Variation 22.9 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 310.43 ng/mL | Geometric Coefficient of Variation 21 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 528.63 ng/mL | Geometric Coefficient of Variation 13.5 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 1014.31 ng/mL | Geometric Coefficient of Variation 30.7 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 1458.44 ng/mL | Geometric Coefficient of Variation 52 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 | 2863.33 ng/mL | Geometric Coefficient of Variation 22.2 |
Secondary
Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 29.46 ng/mL | Geometric Coefficient of Variation 37.9 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 85.3 ng/mL | Geometric Coefficient of Variation 25.9 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 247.73 ng/mL | Geometric Coefficient of Variation 40 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 429.55 ng/mL | Geometric Coefficient of Variation 19.4 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 612.15 ng/mL | Geometric Coefficient of Variation 14.6 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 1126.32 ng/mL | Geometric Coefficient of Variation 71.1 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 | 2645.7 ng/mL | Geometric Coefficient of Variation 31.9 |
Secondary
Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 3.47 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 1.99 Hours |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 1.23 Hours |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 1 Hours |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 1 Hours |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 0.5 Hours |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 | 0 Hours |
Secondary
Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 15.09 ng/mL | Geometric Coefficient of Variation 31.1 |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 14.41 ng/mL | Geometric Coefficient of Variation 23.7 |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 18.24 ng/mL | Geometric Coefficient of Variation 54.1 |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 39.54 ng/mL | Geometric Coefficient of Variation 38.7 |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 51.33 ng/mL | Geometric Coefficient of Variation 70.4 |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 78.7 ng/mL | Geometric Coefficient of Variation 72.8 |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 | 83.43 ng/mL | Geometric Coefficient of Variation 58.1 |
Secondary
Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 6.98 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 8 Hours |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 7.98 Hours |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 7.95 Hours |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 6.99 Hours |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 7 Hours |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 | 18.08 Hours |
Secondary
Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period.
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 95.7 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 261.967 Hours |
| GSK3739937 SD 30 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 359.967 Hours |
| GSK3739937 SD 80 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 358.942 Hours |
| GSK3739937 SD 160 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 359.642 Hours |
| GSK3739937 SD 320 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 359.9 Hours |
| GSK3739937 SD 640 mg | Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 | 360.334 Hours |
Secondary
Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 10 mg, 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Time frame: Up to day 16
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937 | 0.914 Slope of log dose |
Secondary
Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Time frame: Up to day 16
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937 | 0.882 Slope of log dose |
Secondary
Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1 | 1888.173 h*ng/mL | Geometric Coefficient of Variation 24.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1 | 3559.102 h*ng/mL | Geometric Coefficient of Variation 26.3 |
| GSK3739937 SD 30 mg | Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1 | 5893.917 h*ng/mL | Geometric Coefficient of Variation 54.8 |
Secondary
Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1 | 89.33 ng/mL | Geometric Coefficient of Variation 26.9 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1 | 188.65 ng/mL | Geometric Coefficient of Variation 41.1 |
| GSK3739937 SD 30 mg | Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1 | 271.59 ng/mL | Geometric Coefficient of Variation 75.3 |
Secondary
Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1 | 132.12 ng/mL | Geometric Coefficient of Variation 23.3 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1 | 232.07 ng/mL | Geometric Coefficient of Variation 30 |
| GSK3739937 SD 30 mg | Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1 | 375.26 ng/mL | Geometric Coefficient of Variation 50.2 |
Secondary
Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1 | 2 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1 | 2 Hours |
| GSK3739937 SD 30 mg | Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1 | 1.03 Hours |
Secondary
Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1 | 9 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1 | 8 Hours |
| GSK3739937 SD 30 mg | Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1 | 9 Hours |
Secondary
Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 AUC(0-tau) / day 1 AUC(0-tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | 7.728 Ratio |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | 6.993 Ratio |
Secondary
Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 Cmax / day 1 Cmax.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX]) | 5.8 Ratio |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX]) | 4.952 Ratio |
Secondary
Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 C(Tau) / day 1 C(Tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU]) | 6.584 Ratio |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU]) | 5.25 Ratio |
Secondary
Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 | 14592.19 h*ng/mL | Geometric Coefficient of Variation 12.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 | 24888.49 h*ng/mL | Geometric Coefficient of Variation 14.4 |
Secondary
Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14 | 1.7132 L/h | Geometric Coefficient of Variation 12.6 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14 | 2.009 L/h | Geometric Coefficient of Variation 14.4 |
Secondary
Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14 | 766.32 ng/mL | Geometric Coefficient of Variation 16 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14 | 1149.32 ng/mL | Geometric Coefficient of Variation 15.1 |
Secondary
Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 | 588.1557 ng/mL | Geometric Coefficient of Variation 22.5 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 | 990.3205 ng/mL | Geometric Coefficient of Variation 13.2 |
Secondary
Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohorts 3 and 4, steady-state GSK3739937 concentrations was assessed by estimating the slope of concentrations on pre-dose assessments on Days 2-14 (Part 2 cohort 3 and 4) and the day 15 (24-hr post-dose relative to dosing on day 14). PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Up to day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937 | 37.1872 Slope of log dose |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937 | 57.1056 Slope of log dose |
Secondary
Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14 | 85.7725 Hours | Geometric Coefficient of Variation 25.9 |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14 | 72.2484 Hours | Geometric Coefficient of Variation 28.4 |
Secondary
Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14 | 6.95 Hour |
| GSK3739937 Single Dose (SD) 10 mg | Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14 | 7.03 Hour |
Secondary
Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 AUC(0-tau) / day 1 AUC(0-tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | 9.943 Ratio |
Secondary
Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Actual measure type is Ratio. Accumulation ratio calculated as the ratio of day 18 Cmax / day 1 Cmax.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX]) | 7.325 Ratio |
Secondary
Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 C(Tau) / day 1 C(Tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU]) | 9.133 Ratio |
Secondary
Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18 | 58417.64 h*ng/mL | Geometric Coefficient of Variation 21 |
Secondary
Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18 | 1.7118 Litre/ hour (L/h) | Geometric Coefficient of Variation 21 |
Secondary
Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18 | 2748 ng/mL | Geometric Coefficient of Variation 21.1 |
Secondary
Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18 | 2458.275 ng/mL | Geometric Coefficient of Variation 21.2 |
Secondary
Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohort 5, steady state GSK3739937 concentrations was assessed by estimating the slope of the concentrations of pre-dose assessments on Days 2-18 and the day 19 (24-hr post-dose relative to dosing on day 18). PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Up to day 19
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937 | 114.9742 Slope of log dose |
Secondary
Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18 | 78.5264 Hours | Geometric Coefficient of Variation 26.7 |
Secondary
Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18 | 9.01 Hours |
Secondary
Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 AUC(0-tau) / day 1 AUC(0-tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) | 1.76 Ratio |
Secondary
Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 Cmax / day 1 Cmax.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX]) | 1.677 Ratio |
Secondary
Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 C(Tau) / day 1 C(Tau).
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU]) | 1.817 Ratio |
Secondary
Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15 | 169693.1 h*ng/mL | Geometric Coefficient of Variation 31.9 |
Secondary
Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1 | 96434.63 h*ng/mL | Geometric Coefficient of Variation 14.1 |
Secondary
Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15 | 2.9465 L/h | Geometric Coefficient of Variation 31.9 |
Secondary
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1 | 1106.61 ng/mL | Geometric Coefficient of Variation 12.8 |
Secondary
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15 | 1855.67 ng/mL | Geometric Coefficient of Variation 24.1 |
Secondary
Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1 | 250.62 ng/mL | Geometric Coefficient of Variation 36.3 |
Secondary
Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15 | 455.4447 ng/mL | Geometric Coefficient of Variation 46.5 |
Secondary
Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15 | 74.5404 Hours | Geometric Coefficient of Variation 19.1 |
Secondary
Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1 | 0 Hours |
Secondary
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1 | 9.88 Hours |
Secondary
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15 | 10 Hours |
Secondary
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Time frame: Up to day 33
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937 | 0.997 Slope of log dose |
Secondary
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Time frame: Up to day 33
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937 | 0.914 Slope of log dose |
Secondary
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Time frame: Up to day 33
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937 | 1.023 Slope of log dose |
Secondary
Part 3 (Cohort 7) - C24 of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - C24 of GSK3739937 | 316.7 ng/mL | Geometric Coefficient of Variation 29.4 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - C24 of GSK3739937 | 407.5 ng/mL | Geometric Coefficient of Variation 39.7 |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - C24 of GSK3739937 | 153.97 ng/mL | Geometric Coefficient of Variation 91.2 |
Secondary
Part 3 (Cohort 7) Clast of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) Clast of GSK3739937 | 19.76 ng/mL | Geometric Coefficient of Variation 40.8 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) Clast of GSK3739937 | 25.09 ng/mL | Geometric Coefficient of Variation 51.6 |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) Clast of GSK3739937 | 15.44 ng/mL | Geometric Coefficient of Variation 37 |
Secondary
Part 3 (Cohort 7) - CL/F of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - CL/F of GSK3739937 | 2.3082 L/h | Geometric Coefficient of Variation 27.3 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - CL/F of GSK3739937 | 1.698 L/h | Geometric Coefficient of Variation 23.6 |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - CL/F of GSK3739937 | 3.6594 L/h | Geometric Coefficient of Variation 64 |
Secondary
Part 3 (Cohort 7) - T1/2 of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - T1/2 of GSK3739937 | 74.7429 Hours | Geometric Coefficient of Variation 21.5 |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - T1/2 of GSK3739937 | 72.9842 Hours | Geometric Coefficient of Variation 17.5 |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - T1/2 of GSK3739937 | 72.8066 Hours | Geometric Coefficient of Variation 16.9 |
Secondary
Part 3 (Cohort 7) - Tlag of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - Tlag of GSK3739937 | 1 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - Tlag of GSK3739937 | 2 Hours |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - Tlag of GSK3739937 | 0.98 Hours |
Secondary
Part 3 (Cohort 7) - Tlast of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - Tlast of GSK3739937 | 336.75 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - Tlast of GSK3739937 | 360.067 Hours |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - Tlast of GSK3739937 | 267.4 Hours |
Secondary
Part 3 (Cohort 7) - Tmax of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) Single Dose | Part 3 (Cohort 7) - Tmax of GSK3739937 | 9 Hours |
| GSK3739937 Single Dose (SD) 10 mg | Part 3 (Cohort 7) - Tmax of GSK3739937 | 8.42 Hours |
| GSK3739937 SD 30 mg | Part 3 (Cohort 7) - Tmax of GSK3739937 | 6 Hours |