Irritable Bowel Syndrome
Conditions
Keywords
REarranged during Transfection
Brief summary
This FTIH study is designed to assess the safety, tolerability and pharmacokinetic (PK) of escalating single and repeat oral doses of GSK3352589 in normal healthy volunteers. This is a randomized, double-blind (sponsor unblinded), placebo controlled, dose escalation study that will have two parts; Part A and Part B.
Interventions
DRUGGSK3352589
It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.
DRUGMatching Placebo
It will be available across all strengths to match active drug in the form of tablet for oral administration.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 55 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - History of regular bowel habits * Male or Female of non-childbearing potential. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions.
Exclusion criteria
* ALT and bilirubin \>1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Previous Diagnosis of IBS * Estimated Glomerular Filtration Rate \<60 millilter per minute per 1.73 square meter (mL/min/1.73m\^2) * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) * History of Gastroesophageal reflux disease (GERD), dyspepsia, Gastrointestinal (GI) bleeding, diverticulitis, diverticular stricture or other intestinal strictures, GI surgery that could affect motility * Unwillingness or inability to follow the procedures outlined in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Up to 64 days in Cohort 1 | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. |
| Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Up to 30 days in Cohort 2 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. |
| Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Up to 30 days in Cohort 3 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. |
| Part B: Number of Participants With SAEs and Non-SAEs | Up to 25 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. |
| Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | Up to 64 days in Cohort 1 | A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented. |
| Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2 | Up to 30 days in Cohort 2 | A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented. |
| Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3 | Up to 30 days in Cohort 3 | A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented. |
| Part B: Number of Participants With Abnormal Findings After Physical Examination | Up to 25 days | A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented. |
| Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 | Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented. |
| Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 | Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented. |
| Part B: Number of Participants With Abnormal ECG Findings | Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25) | Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented. |
| Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in SBP and DBP in Cohort 2 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in SBP and DBP | Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25) | Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Pulse Rate in Cohort 2 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Pulse Rate | Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25) | Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Body Temperature in Cohort 2 | Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3 | Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Body Temperature | Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25) | Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Up to 64 days in Cohort 1 | The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid). |
| Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Up to 30 days in Cohort 2 | The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid). |
| Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Up to 30 days in Cohort 3 | The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid). |
| Part B: Average BSFS at Indicated Time Points | Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14 | The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid). |
| Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythrocytes in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Erythrocytes | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Hemoglobin in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Hemoglobin | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythrocyte MCV in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Erythrocyte MCV | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Erythrocyte MCH in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Erythrocyte MCH | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Hematocrit in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Hematocrit | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in ALT, AST and Alk Phos | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including albumin, and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Baseline (Day -1) and Day 3 | Blood samples were collected for analysis of clinical chemistry parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part B: Change From Baseline in Albumin, Total Protein | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Baseline (Day-1) and Day 3 | Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). |
| Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Baseline (Day -1) and Day 3 | Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). |
| Part B: Number of Participants With Abnormal Findings for Urine Parameters | Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25) | Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. |
| Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. The PK Parameter population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study. |
| Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including t1/2 following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. |
| Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14 | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods. |
| Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14 | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-24) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods. |
| Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14 | Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods. |
| Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14 | Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods. |
| Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14 | Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods. |
Countries
Australia
Participant flow
Recruitment details
This was a two-part study. Part A was a single dose escalating and Part B was a repeat dose escalating. Participants participated in either Part A or Part B of the study. This was a single center study, conducted at one site in Australia.
Pre-assignment details
A total number of 28 participants were enrolled in Part A and 40 participants were enrolled in Part B of the study. Participants in Part A, participated in one of the 3 Cohorts in Part A and Part B participants participated in one of the 5 Cohorts in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg Participants received single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 3 |
| Part A:Cohort 1:GSK3352589 2mg/Placebo/GSK3352589 15mg/50mg Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 3 |
| Part A:Cohort 1: GSK3352589 2mg/ 5mg/Placebo/ GSK3352589 50mg Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 2 |
| Part A:Cohort 1:GSK3352589 2mg/5mg/15mg/Placebo Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 3 |
| Part A:Cohort 2:GSK3352589 25 mg Fasted/GSK3352589 25 mg Fed Participants received single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 6 |
| Part A: Cohort 2: Placebo Fasted/Placebo Fed Participants received single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 2 |
| Part A:Cohort 3: GSK3352589 150 mg/Placebo Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 2 |
| Part A:Cohort 3: Placebo /GSK3352589 400 mg Participants received single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 2 |
| Part A:Cohort 3: GSK3352589 150 mg/GSK3352589 400 mg Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. | 5 |
| Part B: Placebo BID Participants received repeat oral doses of placebo BID (twice a day) tablet administered for 14 days in Part B of the study. | 10 |
| Part B: GSK3352589 5 mg BID Participants received repeat oral doses of GSK3352589 5 mg BID tablet administered for 14 days in Part B of the study. | 6 |
| Part B: GSK3352589 15 mg BID Participants received repeat oral doses of GSK3352589 15 mg BID tablet administered for 14 days in Part B of the study. | 6 |
| Part B: GSK3352589 50 mg BID Participants received repeat oral doses of GSK3352589 50 mg BID tablet administered for 14 days in Part B of the study. | 6 |
| Part B: GSK3352589 100 mg BID Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study. | 6 |
| Part B: GSK3352589 200 mg BID Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study. | 6 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A: Cohort1 Period4 (Up to 3 Days) | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort1 Washout1 (Up to 14 Days) | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| PartA: Cohort1 Washout2 (Up to 14 Days) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort1 Washout3 (Up to 14 Days) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort3 Period2 (Up to 3 Days) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A: Cohort3 Period2 (Up to 3 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Up to 25 Days) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg | Part A:Cohort 1:GSK3352589 2mg/Placebo/GSK3352589 15mg/50mg | Part A:Cohort 1: GSK3352589 2mg/ 5mg/Placebo/ GSK3352589 50mg | Part A:Cohort 1:GSK3352589 2mg/5mg/15mg/Placebo | Part A:Cohort 2:GSK3352589 25 mg Fasted/GSK3352589 25 mg Fed | Part A: Cohort 2: Placebo Fasted/Placebo Fed | Part A:Cohort 3: GSK3352589 150 mg/Placebo | Part A:Cohort 3: Placebo /GSK3352589 400 mg | Part A:Cohort 3: GSK3352589 150 mg/GSK3352589 400 mg | Part B: Placebo BID | Part B: GSK3352589 5 mg BID | Part B: GSK3352589 15 mg BID | Part B: GSK3352589 50 mg BID | Part B: GSK3352589 100 mg BID | Part B: GSK3352589 200 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.5 Years STANDARD_DEVIATION 8.95 | 43.0 Years STANDARD_DEVIATION 14 | 26.7 Years STANDARD_DEVIATION 4.73 | 33.5 Years STANDARD_DEVIATION 9.19 | 41.0 Years STANDARD_DEVIATION 5.2 | 29.7 Years STANDARD_DEVIATION 8.57 | 34.5 Years STANDARD_DEVIATION 3.54 | 40.5 Years STANDARD_DEVIATION 7.78 | 44.5 Years STANDARD_DEVIATION 0.71 | 28.8 Years STANDARD_DEVIATION 7.43 | 25.5 Years STANDARD_DEVIATION 5.4 | 30.8 Years STANDARD_DEVIATION 8.11 | 33.3 Years STANDARD_DEVIATION 8.45 | 23.3 Years STANDARD_DEVIATION 2.88 | 23.7 Years STANDARD_DEVIATION 4.59 | 32.2 Years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Black or African American | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native-Asian | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 0 Participants | 1 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 |
| Race/Ethnicity, Customized White | 55 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 6 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 8 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 1 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 |
| Sex: Female, Male Male | 66 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 6 Participants | 2 Participants | 2 Participants | 2 Participants | 5 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 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 | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 8 | 5 / 6 | 3 / 6 | 2 / 6 | 2 / 5 | 1 / 2 | 0 / 2 | 3 / 6 | 1 / 6 | 2 / 4 | 3 / 6 | 1 / 5 | 9 / 10 | 5 / 6 | 6 / 6 | 2 / 6 | 5 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 8 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 0.9652 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 83.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 1.446 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 73 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 2.738 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 46.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 5.031 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 63.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 3.648 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 53.3 |
| Part B: GSK3352589 200 mg BID | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 2.372 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 27.8 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 10.75 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 119.1 |
| Cohort 3: GSK3352589 400 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589 | 17.49 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 1.9 |
Primary
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. The PK Parameter population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 0.8452 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 75.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 1.306 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 66.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 2.480 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 49.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 4.630 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 63.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 2.771 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 38.9 |
| Part B: GSK3352589 200 mg BID | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 2.030 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 24.4 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 9.416 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 119.1 |
| Cohort 3: GSK3352589 400 mg | Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589 | 11.67 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 124.7 |
Primary
Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect | 1.294 Hours*Nanogram per milliliter | Standard Error 0.2105 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect | 0.8636 Hours*Nanogram per milliliter | Standard Error 0.163 |
p-value: 0.15790% CI: [0.3876, 1.091]ANOVA
Primary
Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect | 1.019 Hours*Nanogram per milliliter | Standard Error 0.1287 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect | 0.7081 Hours*Nanogram per milliliter | Standard Error 0.1287 |
p-value: 0.11890% CI: [0.5267, 1.019]ANOVA
Primary
Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -5.9 Units per liter | Standard Deviation 11.7 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | 1.3 Units per liter | Standard Deviation 10.3 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | 5.0 Units per liter | Standard Deviation 27.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | 1.0 Units per liter | Standard Deviation 8.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | -1.8 Units per liter | Standard Deviation 15 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -7.3 Units per liter | Standard Deviation 7.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -9.2 Units per liter | Standard Deviation 8.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | -6.2 Units per liter | Standard Deviation 12.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | -0.2 Units per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | -0.2 Units per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | -1.2 Units per liter | Standard Deviation 14.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -10.5 Units per liter | Standard Deviation 8.7 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | -1.8 Units per liter | Standard Deviation 4.7 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | -7.2 Units per liter | Standard Deviation 15.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -17.0 Units per liter | Standard Deviation 6.6 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | 6.0 Units per liter | Standard Deviation 3.2 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | 0.2 Units per liter | Standard Deviation 6.5 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | -5.0 Units per liter | Standard Deviation 5.2 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | Alk Phos; Day 3 | -3.6 Units per liter | Standard Deviation 8.2 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | AST; Day 3 | -3.4 Units per liter | Standard Deviation 5.5 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3 | ALT; Day 3 | 8.0 Units per liter | Standard Deviation 9.3 |
Primary
Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including albumin, and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -3.1 Grams per liter | Standard Deviation 3.5 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -3.5 Grams per liter | Standard Deviation 5.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -1.8 Grams per liter | Standard Deviation 4.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -2.5 Grams per liter | Standard Deviation 6.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -3.5 Grams per liter | Standard Deviation 4.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -5.0 Grams per liter | Standard Deviation 7.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -3.2 Grams per liter | Standard Deviation 3.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -3.3 Grams per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -4.8 Grams per liter | Standard Deviation 3.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -6.2 Grams per liter | Standard Deviation 7.1 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -2.8 Grams per liter | Standard Deviation 2.2 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -2.0 Grams per liter | Standard Deviation 3.6 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Albumin; Day 3 | -3.8 Grams per liter | Standard Deviation 2.8 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3 | Total Protein; Day 3 | -2.6 Grams per liter | Standard Deviation 3.4 |
Primary
Part A: Change From Baseline in Albumin and Total Protein in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Albumin; Day 3 | -1.0 Grams per liter | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Total Protein; Day 3 | -2.5 Grams per liter | Standard Deviation 0.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Total Protein; Day 3 | -4.5 Grams per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Albumin; Day 3 | -2.0 Grams per liter | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Albumin; Day 3 | -1.2 Grams per liter | Standard Deviation 2.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Total Protein; Day 3 | -1.5 Grams per liter | Standard Deviation 5.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Albumin; Day 3 | -1.7 Grams per liter | Standard Deviation 2.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Albumin and Total Protein in Cohort 2 | Total Protein; Day 3 | -3.8 Grams per liter | Standard Deviation 2.9 |
Primary
Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | ALT; Day 3 | -1.5 Units per liter | Standard Deviation 0.7 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | Alk Phos; Day 3 | -6.0 Units per liter | Standard Deviation 5.7 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | AST; Day 3 | -4.5 Units per liter | Standard Deviation 0.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | ALT; Day 3 | -0.5 Units per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | Alk Phos; Day 3 | -10.0 Units per liter | Standard Deviation 4.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | AST; Day 3 | -1.5 Units per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | AST; Day 3 | -4.5 Units per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | ALT; Day 3 | 0.2 Units per liter | Standard Deviation 1.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | Alk Phos; Day 3 | 0.8 Units per liter | Standard Deviation 5.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | ALT; Day 3 | -2.3 Units per liter | Standard Deviation 5.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | Alk Phos; Day 3 | -2.0 Units per liter | Standard Deviation 4.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2 | AST; Day 3 | -4.3 Units per liter | Standard Deviation 4.2 |
Primary
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | -0.05 10^9 cells per liter | Standard Deviation 0.12 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | 0.01 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -1.01 10^9 cells per liter | Standard Deviation 1.06 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -15.0 10^9 cells per liter | Standard Deviation 34.6 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.37 10^9 cells per liter | Standard Deviation 0.4 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.66 10^9 cells per liter | Standard Deviation 1.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -4.8 10^9 cells per liter | Standard Deviation 34.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.73 10^9 cells per liter | Standard Deviation 1.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | -0.08 10^9 cells per liter | Standard Deviation 0.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.10 10^9 cells per liter | Standard Deviation 0.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.88 10^9 cells per liter | Standard Deviation 0.95 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.32 10^9 cells per liter | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.95 10^9 cells per liter | Standard Deviation 1.33 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.05 10^9 cells per liter | Standard Deviation 0.14 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -22.5 10^9 cells per liter | Standard Deviation 45.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | -0.13 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.60 10^9 cells per liter | Standard Deviation 1.55 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | -0.08 10^9 cells per liter | Standard Deviation 0.12 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | -0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.43 10^9 cells per liter | Standard Deviation 0.36 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.23 10^9 cells per liter | Standard Deviation 0.7 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | 2.2 10^9 cells per liter | Standard Deviation 32.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.82 10^9 cells per liter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.58 10^9 cells per liter | Standard Deviation 2.64 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | 0.04 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | -0.04 10^9 cells per liter | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.50 10^9 cells per liter | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -8.0 10^9 cells per liter | Standard Deviation 43.7 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.16 10^9 cells per liter | Standard Deviation 2.76 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.53 10^9 cells per liter | Standard Deviation 0.94 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | -0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.60 10^9 cells per liter | Standard Deviation 0.85 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -23.3 10^9 cells per liter | Standard Deviation 13.9 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | 0.03 10^9 cells per liter | Standard Deviation 0.08 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | 0.03 10^9 cells per liter | Standard Deviation 0.31 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Monocytes; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Neutrophils; Day 3 | -0.36 10^9 cells per liter | Standard Deviation 0.9 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Eosinophils; Day 3 | 0.04 10^9 cells per liter | Standard Deviation 0.05 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Platelets; Day 3 | -46.6 10^9 cells per liter | Standard Deviation 36.5 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Basophils; Day 3 | -0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Leukocytes ;Day 3 | -0.52 10^9 cells per liter | Standard Deviation 0.94 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3 | Lymphocytes; Day 3 | -0.16 10^9 cells per liter | Standard Deviation 0.29 |
Primary
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Basophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Platelets; Day 3 | -7.0 10^9 cells per liter | Standard Deviation 11.3 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Neutrophils; Day 3 | -1.00 10^9 cells per liter | Standard Deviation 0.42 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Eosinophils; Day 3 | 0.05 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Leukocytes ;Day 3 | -0.90 10^9 cells per liter | Standard Deviation 0.57 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Lymphocytes; Day 3 | 0.10 10^9 cells per liter | Standard Deviation 0.14 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Monocytes; Day 3 | -0.05 10^9 cells per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Platelets; Day 3 | -45.0 10^9 cells per liter | Standard Deviation 26.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Monocytes; Day 3 | -0.05 10^9 cells per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Lymphocytes; Day 3 | 0.10 10^9 cells per liter | Standard Deviation 0.14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Neutrophils; Day 3 | -0.85 10^9 cells per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Leukocytes ;Day 3 | -0.75 10^9 cells per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Eosinophils; Day 3 | 0.05 10^9 cells per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Basophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Monocytes; Day 3 | -0.02 10^9 cells per liter | Standard Deviation 0.15 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Basophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Eosinophils; Day 3 | 0.00 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Lymphocytes; Day 3 | 0.25 10^9 cells per liter | Standard Deviation 0.65 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Neutrophils; Day 3 | -1.25 10^9 cells per liter | Standard Deviation 1.97 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Platelets; Day 3 | -7.2 10^9 cells per liter | Standard Deviation 5.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Leukocytes ;Day 3 | -1.00 10^9 cells per liter | Standard Deviation 2.44 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Lymphocytes; Day 3 | 0.12 10^9 cells per liter | Standard Deviation 0.58 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Leukocytes ;Day 3 | -1.68 10^9 cells per liter | Standard Deviation 2.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Platelets; Day 3 | -29.2 10^9 cells per liter | Standard Deviation 27 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Eosinophils; Day 3 | 0.03 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Basophils; Day 3 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Neutrophils; Day 3 | -1.73 10^9 cells per liter | Standard Deviation 1.84 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2 | Monocytes; Day 3 | -0.08 10^9 cells per liter | Standard Deviation 0.1 |
Primary
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | 0.80 Micromoles per liter | Standard Deviation 1.49 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | -0.7 Micromoles per liter | Standard Deviation 7 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 1.2 Micromoles per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | -2.5 Micromoles per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 1.0 Micromoles per liter | Standard Deviation 4.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | 0.85 Micromoles per liter | Standard Deviation 1.86 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | 0.52 Micromoles per liter | Standard Deviation 0.74 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 1.2 Micromoles per liter | Standard Deviation 3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | -2.3 Micromoles per liter | Standard Deviation 8.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | 1.7 Micromoles per liter | Standard Deviation 8.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 2.2 Micromoles per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | 1.38 Micromoles per liter | Standard Deviation 0.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | 0.4 Micromoles per liter | Standard Deviation 11.1 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 1.6 Micromoles per liter | Standard Deviation 3.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | 1.58 Micromoles per liter | Standard Deviation 1 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | -0.7 Micromoles per liter | Standard Deviation 4.4 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | -1.15 Micromoles per liter | Standard Deviation 1.84 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | 1.5 Micromoles per liter | Standard Deviation 5 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Direct bilirubin; Day 3 | -0.14 Micromoles per liter | Standard Deviation 1 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Creatinine; Day 3 | -3.0 Micromoles per liter | Standard Deviation 13.4 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3 | Bilirubin; Day 3 | 2.2 Micromoles per liter | Standard Deviation 3.7 |
Primary
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Bilirubin; Day 3 | 3.5 Micromoles per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Direct bilirubin; Day 3 | 0.65 Micromoles per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Creatinine; Day 3 | -8.5 Micromoles per liter | Standard Deviation 7.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Bilirubin; Day 3 | 2.0 Micromoles per liter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Direct bilirubin; Day 3 | 0.50 Micromoles per liter | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Creatinine; Day 3 | -8.0 Micromoles per liter | Standard Deviation 8.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Creatinine; Day 3 | -2.2 Micromoles per liter | Standard Deviation 4.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Bilirubin; Day 3 | 1.5 Micromoles per liter | Standard Deviation 3.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Direct bilirubin; Day 3 | 0.38 Micromoles per liter | Standard Deviation 0.87 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Bilirubin; Day 3 | -0.7 Micromoles per liter | Standard Deviation 4.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Direct bilirubin; Day 3 | -0.10 Micromoles per liter | Standard Deviation 1.33 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2 | Creatinine; Day 3 | -5.3 Micromoles per liter | Standard Deviation 4.3 |
Primary
Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -0.09 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | -0.09 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.04 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.09 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | -0.07 Celsius | Standard Deviation 0.41 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | -0.18 Celsius | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.13 Celsius | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | -0.22 Celsius | Standard Deviation 0.43 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.27 Celsius | Standard Deviation 0.28 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | -0.45 Celsius | Standard Deviation 0.58 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -0.22 Celsius | Standard Deviation 0.43 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.22 Celsius | Standard Deviation 0.43 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | -0.15 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -0.15 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.15 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | 0.00 Celsius | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.30 Celsius | Standard Deviation 0.42 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | -0.16 Celsius | Standard Deviation 0.59 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.58 Celsius | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -0.12 Celsius | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.12 Celsius | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | -0.12 Celsius | Standard Deviation 0.34 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | -0.22 Celsius | Standard Deviation 0.29 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | 0.10 Celsius | Standard Deviation 0.48 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 3 | 0.26 Celsius | Standard Deviation 0.48 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.20 Celsius | Standard Deviation 0.24 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -0.20 Celsius | Standard Deviation 0.24 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | -0.20 Celsius | Standard Deviation 0.24 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3 | Day 2 | 0.00 Celsius | Standard Deviation 0.25 |
Primary
Part A: Change From Baseline in Body Temperature in Cohort 2
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 2 | -0.15 Celsius | Standard Deviation 0.07 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 1 Hour Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 4 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 12 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 3 | -0.20 Celsius | Standard Deviation 0.14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 3 | -0.35 Celsius | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 12 Hours Post dose | -0.10 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 1 Hour Post dose | -0.10 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 4 Hours Post dose | -0.10 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 2 | -0.15 Celsius | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 4 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 12 Hours Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 3 | -0.10 Celsius | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 2 | -0.33 Celsius | Standard Deviation 0.73 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 1 Hour Post dose | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 12 Hours Post dose | 0.00 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 2 | 0.03 Celsius | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 4 Hours Post dose | 0.00 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 1; 1 Hour Post dose | 0.00 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Body Temperature in Cohort 2 | Day 3 | -0.22 Celsius | Standard Deviation 0.56 |
Primary
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | -0.04 Millimoles per liter | Standard Deviation 0.28 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.43 Millimoles per liter | Standard Deviation 1.11 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | 0.01 Millimoles per liter | Standard Deviation 0.69 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.049 Millimoles per liter | Standard Deviation 0.108 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -2.5 Millimoles per liter | Standard Deviation 2.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.62 Millimoles per liter | Standard Deviation 0.74 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -2.7 Millimoles per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | -0.03 Millimoles per liter | Standard Deviation 0.27 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | 0.05 Millimoles per liter | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.005 Millimoles per liter | Standard Deviation 0.134 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.075 Millimoles per liter | Standard Deviation 0.107 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -2.3 Millimoles per liter | Standard Deviation 3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | 0.13 Millimoles per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.68 Millimoles per liter | Standard Deviation 1.39 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | 0.25 Millimoles per liter | Standard Deviation 0.82 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.060 Millimoles per liter | Standard Deviation 0.145 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | 0.22 Millimoles per liter | Standard Deviation 0.36 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | 0.10 Millimoles per liter | Standard Deviation 0.23 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -1.8 Millimoles per liter | Standard Deviation 1.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.13 Millimoles per liter | Standard Deviation 1.22 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.054 Millimoles per liter | Standard Deviation 0.152 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.14 Millimoles per liter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | -0.08 Millimoles per liter | Standard Deviation 0.16 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -2.0 Millimoles per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | -0.32 Millimoles per liter | Standard Deviation 1.32 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.063 Millimoles per liter | Standard Deviation 0.038 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.55 Millimoles per liter | Standard Deviation 1.2 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | -1.0 Millimoles per liter | Standard Deviation 2.6 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | -0.23 Millimoles per liter | Standard Deviation 0.64 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | -0.03 Millimoles per liter | Standard Deviation 0.27 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Sodium; Day 3 | 1.0 Millimoles per liter | Standard Deviation 1 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Glucose; Day 3 | 0.22 Millimoles per liter | Standard Deviation 0.94 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Potassium; Day 3 | 0.16 Millimoles per liter | Standard Deviation 0.17 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Calcium; Day 3 | -0.124 Millimoles per liter | Standard Deviation 0.067 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3 | Urea; Day 3 | -0.48 Millimoles per liter | Standard Deviation 0.57 |
Primary
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Sodium; Day 3 | 0.0 Millimoles per liter | Standard Deviation 0 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Potassium; Day 3 | 0.05 Millimoles per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Urea; Day 3 | -1.30 Millimoles per liter | Standard Deviation 0.14 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Glucose; Day 3 | 0.35 Millimoles per liter | Standard Deviation 0.21 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Calcium; Day 3 | -0.075 Millimoles per liter | Standard Deviation 0.078 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Calcium; Day 3 | -0.110 Millimoles per liter | Standard Deviation 0.071 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Glucose; Day 3 | 0.30 Millimoles per liter | Standard Deviation 0.14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Potassium; Day 3 | 0.05 Millimoles per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Sodium; Day 3 | 1.0 Millimoles per liter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Urea; Day 3 | -1.00 Millimoles per liter | Standard Deviation 0.57 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Sodium; Day 3 | 0.7 Millimoles per liter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Calcium; Day 3 | 0.022 Millimoles per liter | Standard Deviation 0.12 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Glucose; Day 3 | -0.45 Millimoles per liter | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Urea; Day 3 | 0.37 Millimoles per liter | Standard Deviation 1.15 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Potassium; Day 3 | -0.17 Millimoles per liter | Standard Deviation 0.27 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Calcium; Day 3 | -0.037 Millimoles per liter | Standard Deviation 0.105 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Urea; Day 3 | -0.03 Millimoles per liter | Standard Deviation 1.32 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Sodium; Day 3 | 0.5 Millimoles per liter | Standard Deviation 2.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Potassium; Day 3 | -0.13 Millimoles per liter | Standard Deviation 0.29 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2 | Glucose; Day 3 | -0.55 Millimoles per liter | Standard Deviation 0.52 |
Primary
Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | -0.19 Picogram | Standard Deviation 0.71 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | -0.37 Picogram | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | -0.13 Picogram | Standard Deviation 0.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | -0.25 Picogram | Standard Deviation 0.66 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | -0.84 Picogram | Standard Deviation 0.52 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | 0.08 Picogram | Standard Deviation 0.35 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3 | 0.54 Picogram | Standard Deviation 0.43 |
Primary
Part A: Change From Baseline in Erythrocyte MCH in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythrocyte MCH in Cohort 2 | 0.20 Picogram | Standard Deviation 0.28 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythrocyte MCH in Cohort 2 | 0.20 Picogram | Standard Deviation 0.28 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythrocyte MCH in Cohort 2 | 0.20 Picogram | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythrocyte MCH in Cohort 2 | 0.27 Picogram | Standard Deviation 0.23 |
Primary
Part A: Change From Baseline in Erythrocyte MCV in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythrocyte MCV in Cohort 2 | -2.0 Femtoliter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythrocyte MCV in Cohort 2 | -2.0 Femtoliter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythrocyte MCV in Cohort 2 | 1.5 Femtoliter | Standard Deviation 3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythrocyte MCV in Cohort 2 | 0.7 Femtoliter | Standard Deviation 2.6 |
Primary
Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 0.9 Femtoliter | Standard Deviation 1.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 0.2 Femtoliter | Standard Deviation 1.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 1.5 Femtoliter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 1.7 Femtoliter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 1.6 Femtoliter | Standard Deviation 1.1 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 0.8 Femtoliter | Standard Deviation 0.8 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3 | 1.0 Femtoliter | Standard Deviation 1.6 |
Primary
Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | 0.029 10^12 cells per liter | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | 0.275 10^12 cells per liter | Standard Deviation 0.321 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | -0.073 10^12 cells per liter | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | 0.112 10^12 cells per liter | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | 0.120 10^12 cells per liter | Standard Deviation 0.373 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | 0.063 10^12 cells per liter | Standard Deviation 0.094 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3 | -0.132 10^12 cells per liter | Standard Deviation 0.132 |
Primary
Part A: Change From Baseline in Erythrocytes in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Erythrocytes in Cohort 2 | 0.110 10^12 cells per liter | Standard Deviation 0.156 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Erythrocytes in Cohort 2 | 0.150 10^12 cells per liter | Standard Deviation 0.269 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Erythrocytes in Cohort 2 | 0.167 10^12 cells per liter | Standard Deviation 0.118 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Erythrocytes in Cohort 2 | 0.042 10^12 cells per liter | Standard Deviation 0.157 |
Primary
Part A: Change From Baseline in Hematocrit in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.007 Proportion of red blood cells in blood | Standard Deviation 0.021 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.025 Proportion of red blood cells in blood | Standard Deviation 0.027 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.002 Proportion of red blood cells in blood | Standard Deviation 0.029 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.017 Proportion of red blood cells in blood | Standard Deviation 0.031 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.018 Proportion of red blood cells in blood | Standard Deviation 0.026 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | 0.007 Proportion of red blood cells in blood | Standard Deviation 0.008 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Hematocrit in Cohort 1 and 3 | -0.008 Proportion of red blood cells in blood | Standard Deviation 0.015 |
Primary
Part A: Change From Baseline in Hematocrit in Cohort 2
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Hematocrit in Cohort 2 | 0.005 Proportion of red blood cells in blood | Standard Deviation 0.021 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Hematocrit in Cohort 2 | 0.010 Proportion of red blood cells in blood | Standard Deviation 0.028 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Hematocrit in Cohort 2 | 0.023 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Hematocrit in Cohort 2 | 0.008 Proportion of red blood cells in blood | Standard Deviation 0.015 |
Primary
Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | 0.0 Grams per liter | Standard Deviation 8.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | 6.2 Grams per liter | Standard Deviation 9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | -2.5 Grams per liter | Standard Deviation 9.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | 2.0 Grams per liter | Standard Deviation 9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | -0.8 Grams per liter | Standard Deviation 8.8 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | 2.2 Grams per liter | Standard Deviation 4.3 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3 | -1.2 Grams per liter | Standard Deviation 4.3 |
Primary
Part A: Change From Baseline in Hemoglobin in Cohort 2
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Hemoglobin in Cohort 2 | 4.0 Grams per liter | Standard Deviation 2.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Hemoglobin in Cohort 2 | 5.5 Grams per liter | Standard Deviation 9.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Hemoglobin in Cohort 2 | 5.8 Grams per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Hemoglobin in Cohort 2 | 2.3 Grams per liter | Standard Deviation 3.8 |
Primary
Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -6.42 Beats per minute | Standard Deviation 5.91 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 2.38 Beats per minute | Standard Deviation 6.34 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | 0.54 Beats per minute | Standard Deviation 7.17 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -1.46 Beats per minute | Standard Deviation 9.11 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -3.79 Beats per minute | Standard Deviation 6.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -3.25 Beats per minute | Standard Deviation 4.39 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 0.75 Beats per minute | Standard Deviation 3.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -4.92 Beats per minute | Standard Deviation 5.98 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -3.33 Beats per minute | Standard Deviation 7.77 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | -0.08 Beats per minute | Standard Deviation 10.84 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 5.83 Beats per minute | Standard Deviation 6.04 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -4.67 Beats per minute | Standard Deviation 6.59 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -3.00 Beats per minute | Standard Deviation 6.66 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | -1.75 Beats per minute | Standard Deviation 9.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -2.42 Beats per minute | Standard Deviation 6.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 6.00 Beats per minute | Standard Deviation 3.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -3.25 Beats per minute | Standard Deviation 6.93 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -0.75 Beats per minute | Standard Deviation 7.96 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | 2.08 Beats per minute | Standard Deviation 4.57 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | 0.50 Beats per minute | Standard Deviation 7.06 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 0.40 Beats per minute | Standard Deviation 8.93 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -3.60 Beats per minute | Standard Deviation 7.21 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -6.90 Beats per minute | Standard Deviation 5.03 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -4.00 Beats per minute | Standard Deviation 7.44 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | -2.50 Beats per minute | Standard Deviation 10.62 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | -2.08 Beats per minute | Standard Deviation 5.44 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -2.75 Beats per minute | Standard Deviation 5.69 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -3.67 Beats per minute | Standard Deviation 4.7 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -2.83 Beats per minute | Standard Deviation 2.14 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 2.33 Beats per minute | Standard Deviation 3.88 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 2 | -1.60 Beats per minute | Standard Deviation 3.6 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post dose | -3.20 Beats per minute | Standard Deviation 5.38 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post dose | 2.40 Beats per minute | Standard Deviation 6.44 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 3 | 0.50 Beats per minute | Standard Deviation 5.15 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post dose | -3.40 Beats per minute | Standard Deviation 3.17 |
Primary
Part A: Change From Baseline in Pulse Rate in Cohort 2
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 1 Hour Post dose | 1.50 Beats per minute | Standard Deviation 1.41 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 12 Hours Post dose | 7.00 Beats per minute | Standard Deviation 2.12 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 2 | 1.25 Beats per minute | Standard Deviation 3.89 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 3 | 8.00 Beats per minute | Standard Deviation 4.95 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 4 Hours Post dose | 1.75 Beats per minute | Standard Deviation 2.47 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 1 Hour Post dose | 7.50 Beats per minute | Standard Deviation 0.71 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 2 | 3.00 Beats per minute | Standard Deviation 4.24 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 4 Hours Post dose | -1.00 Beats per minute | Standard Deviation 2.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 12 Hours Post dose | 9.25 Beats per minute | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 3 | 4.75 Beats per minute | Standard Deviation 3.18 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 2 | 4.33 Beats per minute | Standard Deviation 4.74 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 12 Hours Post dose | 9.33 Beats per minute | Standard Deviation 3.42 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 3 | 6.92 Beats per minute | Standard Deviation 7.12 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 4 Hours Post dose | -1.33 Beats per minute | Standard Deviation 3.87 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 1 Hour Post dose | 0.42 Beats per minute | Standard Deviation 4.98 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 12 Hours Post dose | 7.92 Beats per minute | Standard Deviation 2.76 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 3 | 7.58 Beats per minute | Standard Deviation 8.29 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 4 Hours Post dose | 2.75 Beats per minute | Standard Deviation 3.95 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 1; 1 Hour Post dose | 9.08 Beats per minute | Standard Deviation 4.33 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Pulse Rate in Cohort 2 | Day 2 | 3.17 Beats per minute | Standard Deviation 5.39 |
Primary
Part A: Change From Baseline in SBP and DBP in Cohort 2
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 1 Hour Post dose | 1.25 Millimeters of mercury | Standard Deviation 3.89 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 12 Hours Post dose | -5.25 Millimeters of mercury | Standard Deviation 2.47 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 2 | -6.75 Millimeters of mercury | Standard Deviation 5.3 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 2 | -3.50 Millimeters of mercury | Standard Deviation 2.12 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 3 | -0.25 Millimeters of mercury | Standard Deviation 0.35 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 4 Hours Post dose | -1.75 Millimeters of mercury | Standard Deviation 1.06 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 3 | 1.50 Millimeters of mercury | Standard Deviation 8.49 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 12 Hours Post dose | 1.75 Millimeters of mercury | Standard Deviation 9.55 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 4 Hours Post dose | -3.25 Millimeters of mercury | Standard Deviation 3.18 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 1 Hour Post dose | 3.75 Millimeters of mercury | Standard Deviation 3.89 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 12 Hours Post dose | -3.00 Millimeters of mercury | Standard Deviation 2.83 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 2 | -5.25 Millimeters of mercury | Standard Deviation 6.72 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 12 Hours Post dose | 10.75 Millimeters of mercury | Standard Deviation 15.91 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 3 | 0.75 Millimeters of mercury | Standard Deviation 7.42 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 1 Hour Post dose | 6.00 Millimeters of mercury | Standard Deviation 8.49 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 2 | -3.75 Millimeters of mercury | Standard Deviation 4.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 3 | 6.75 Millimeters of mercury | Standard Deviation 10.96 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 4 Hours Post dose | -5.00 Millimeters of mercury | Standard Deviation 3.54 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 4 Hours Post dose | -6.50 Millimeters of mercury | Standard Deviation 9.19 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 1 Hour Post dose | -5.75 Millimeters of mercury | Standard Deviation 2.47 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 2 | -1.92 Millimeters of mercury | Standard Deviation 4.41 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 12 Hours Post dose | 1.50 Millimeters of mercury | Standard Deviation 10.84 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 12 Hours Post dose | -2.67 Millimeters of mercury | Standard Deviation 6.92 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 1 Hour Post dose | 1.67 Millimeters of mercury | Standard Deviation 6.23 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 4 Hours Post dose | -5.17 Millimeters of mercury | Standard Deviation 11.44 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 3 | 3.58 Millimeters of mercury | Standard Deviation 6.94 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 2 | -7.58 Millimeters of mercury | Standard Deviation 5.18 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 4 Hours Post dose | -1.67 Millimeters of mercury | Standard Deviation 7.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 1 Hour Post dose | 3.75 Millimeters of mercury | Standard Deviation 9.68 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 3 | -4.50 Millimeters of mercury | Standard Deviation 8.06 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 3 | 2.08 Millimeters of mercury | Standard Deviation 5.01 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 1 Hour Post dose | -6.58 Millimeters of mercury | Standard Deviation 9.91 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 4 Hours Post dose | -6.25 Millimeters of mercury | Standard Deviation 10.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 1; 12 Hours Post dose | 1.50 Millimeters of mercury | Standard Deviation 11.66 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 2 | -5.00 Millimeters of mercury | Standard Deviation 9.77 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | SBP; Day 3 | 1.00 Millimeters of mercury | Standard Deviation 7.54 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 1 Hour Post dose | -4.25 Millimeters of mercury | Standard Deviation 5.67 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 4 Hours Post dose | -4.75 Millimeters of mercury | Standard Deviation 5.99 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 1; 12 Hours Post dose | -6.00 Millimeters of mercury | Standard Deviation 6.87 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in SBP and DBP in Cohort 2 | DBP; Day 2 | -2.75 Millimeters of mercury | Standard Deviation 3.49 |
Primary
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -2.42 Millimeters of mercury | Standard Deviation 10 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -2.92 Millimeters of mercury | Standard Deviation 5.67 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | -1.29 Millimeters of mercury | Standard Deviation 11.32 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | -1.25 Millimeters of mercury | Standard Deviation 9.61 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | 2.04 Millimeters of mercury | Standard Deviation 5.87 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | -3.63 Millimeters of mercury | Standard Deviation 11.05 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | -0.54 Millimeters of mercury | Standard Deviation 5.62 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | 1.13 Millimeters of mercury | Standard Deviation 6.3 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -2.13 Millimeters of mercury | Standard Deviation 4.71 |
| Part A: Cohort 1: Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 2.21 Millimeters of mercury | Standard Deviation 8.65 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | -8.67 Millimeters of mercury | Standard Deviation 5.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | -0.42 Millimeters of mercury | Standard Deviation 5.33 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -2.58 Millimeters of mercury | Standard Deviation 7.91 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | -0.67 Millimeters of mercury | Standard Deviation 3.89 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | -1.75 Millimeters of mercury | Standard Deviation 4.71 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -4.50 Millimeters of mercury | Standard Deviation 5.74 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -4.42 Millimeters of mercury | Standard Deviation 6.58 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | -3.83 Millimeters of mercury | Standard Deviation 10.11 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | -5.83 Millimeters of mercury | Standard Deviation 5.86 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | -2.67 Millimeters of mercury | Standard Deviation 7.72 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | 1.75 Millimeters of mercury | Standard Deviation 4.71 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | -2.08 Millimeters of mercury | Standard Deviation 11.72 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | 2.67 Millimeters of mercury | Standard Deviation 5.65 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | -1.33 Millimeters of mercury | Standard Deviation 13.56 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 1.08 Millimeters of mercury | Standard Deviation 11.33 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | -1.83 Millimeters of mercury | Standard Deviation 5.39 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -2.25 Millimeters of mercury | Standard Deviation 4.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -1.42 Millimeters of mercury | Standard Deviation 9.77 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | -0.42 Millimeters of mercury | Standard Deviation 16.59 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -3.08 Millimeters of mercury | Standard Deviation 5.29 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -1.17 Millimeters of mercury | Standard Deviation 4.01 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | 3.75 Millimeters of mercury | Standard Deviation 11.04 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | -1.50 Millimeters of mercury | Standard Deviation 6.43 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | 2.25 Millimeters of mercury | Standard Deviation 9.95 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | 1.92 Millimeters of mercury | Standard Deviation 7.05 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | 3.00 Millimeters of mercury | Standard Deviation 9.72 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -5.75 Millimeters of mercury | Standard Deviation 5.33 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | 1.08 Millimeters of mercury | Standard Deviation 7.34 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -2.17 Millimeters of mercury | Standard Deviation 10.87 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 3.00 Millimeters of mercury | Standard Deviation 10.39 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | -3.60 Millimeters of mercury | Standard Deviation 14.72 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -3.40 Millimeters of mercury | Standard Deviation 7.54 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | 1.00 Millimeters of mercury | Standard Deviation 10.31 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | -2.70 Millimeters of mercury | Standard Deviation 12.26 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 3.10 Millimeters of mercury | Standard Deviation 9.15 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | -3.30 Millimeters of mercury | Standard Deviation 10.12 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | -2.10 Millimeters of mercury | Standard Deviation 6.07 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -4.10 Millimeters of mercury | Standard Deviation 8.13 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -5.40 Millimeters of mercury | Standard Deviation 3.44 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | -2.20 Millimeters of mercury | Standard Deviation 4.27 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | 0.33 Millimeters of mercury | Standard Deviation 4.01 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | 0.67 Millimeters of mercury | Standard Deviation 4.17 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | -1.08 Millimeters of mercury | Standard Deviation 5.3 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | 1.50 Millimeters of mercury | Standard Deviation 2.53 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | 0.75 Millimeters of mercury | Standard Deviation 4.97 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | -0.17 Millimeters of mercury | Standard Deviation 5.34 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | -1.75 Millimeters of mercury | Standard Deviation 3.27 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 1.33 Millimeters of mercury | Standard Deviation 4.07 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | 1.58 Millimeters of mercury | Standard Deviation 5.55 |
| Part B: GSK3352589 200 mg BID | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | 1.17 Millimeters of mercury | Standard Deviation 4.77 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 1 Hour Post dose | 4.20 Millimeters of mercury | Standard Deviation 2.59 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 3 | 0.60 Millimeters of mercury | Standard Deviation 5.9 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 1 Hour Post dose | -0.10 Millimeters of mercury | Standard Deviation 3.45 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 3 | 3.80 Millimeters of mercury | Standard Deviation 4.91 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 2 | 3.60 Millimeters of mercury | Standard Deviation 4.92 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 12 Hours Post dose | 0.40 Millimeters of mercury | Standard Deviation 7.99 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 2 | -5.00 Millimeters of mercury | Standard Deviation 5.78 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | DBP; Day 1; 4 Hours Post dose | 6.50 Millimeters of mercury | Standard Deviation 2.06 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 12 Hours Post dose | 3.90 Millimeters of mercury | Standard Deviation 6.69 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3 | SBP; Day 1; 4 Hours Post dose | 1.40 Millimeters of mercury | Standard Deviation 1.29 |
Primary
Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect
Blood samples were collected from participants for pharmacokinetic analysis following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect | 0.5397 Nanogram per milliliter | Geometric Coefficient of Variation 38.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect | 0.4317 Nanogram per milliliter | Geometric Coefficient of Variation 15.2 |
p-value: 0.20490% CI: [0.594, 1.077]ANOVA
Primary
Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.2339 Nanogram per milliliter | Geometric Coefficient of Variation 74.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.2919 Nanogram per milliliter | Geometric Coefficient of Variation 58.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.5541 Nanogram per milliliter | Geometric Coefficient of Variation 40 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.7318 Nanogram per milliliter | Geometric Coefficient of Variation 65.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.5397 Nanogram per milliliter | Geometric Coefficient of Variation 38.6 |
| Part B: GSK3352589 200 mg BID | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 0.4317 Nanogram per milliliter | Geometric Coefficient of Variation 15.2 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 1.325 Nanogram per milliliter | Geometric Coefficient of Variation 111.6 |
| Cohort 3: GSK3352589 400 mg | Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589 | 1.157 Nanogram per milliliter | Geometric Coefficient of Variation 72.5 |
Primary
Part A: Number of Participants With Abnormal ECG Findings in Cohort 2
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline; (Day 1;pre dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline; (Day 1;pre dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline; (Day 1;pre dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline; (Day 1;pre dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal ECG Findings in Cohort 2 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal NCS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal NCS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 2; Abnormal CS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 1 Hour Post-dose; Abnormal CS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Day 1; 12 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3 | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1
A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time frame: Up to 64 days in Cohort 1
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1 | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time frame: Up to 30 days in Cohort 2
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2 | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time frame: Up to 30 days in Cohort 3
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3 | 1 Participants |
Primary
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Time frame: Baseline (Day-1) and Day 3
Population: Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Bilirubin; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Occult blood; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Urobilinogen; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Nitrite; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Protein; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | pH; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Ketones; Day 3 | 0 Participants |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3 | Glucose; Baseline (Day -1) | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Time frame: Baseline (Day -1) and Day 3
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Nitrite; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Leukocyte esterase; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Ketones; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Bilirubin; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Specific gravity; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Glucose; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | pH; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Occult blood; Baseline (Day -1) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Urobilinogen; Day 3 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2 | Protein; Baseline (Day -1) | 0 Participants |
Primary
Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time frame: Up to 64 days in Cohort 1
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 4 | 1 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 2 | 3 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 5 | 4 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 3 | 3 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 1 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 6 | 3 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 4 | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 6 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 5 | 3 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 3 | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 2 | 3 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 5 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 2 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 3 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 4 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 6 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 7 | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 5 | 3 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 3 | 3 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 6 | 2 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 1 | 1 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 4 | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 3 | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 4 | 3 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 5 | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 6 | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1 | Type 2 | 0 Participants |
Primary
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time frame: Up to 30 days in Cohort 2
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 1 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 3 | 1 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 6 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 5 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 4 | 1 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 4 | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 5 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 3 | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 6 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 4 | 3 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 2 | 3 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 3 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 5 | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 6 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 3 | 3 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 6 | 1 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 2 | 1 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 5 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2 | Type 4 | 1 Participants |
Primary
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time frame: Up to 30 days in Cohort 3
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 2 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 5 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 4 | 2 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 1 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 6 | 1 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 3 | 2 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 4 | 5 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 1 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 2 | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 3 | 4 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 5 | 3 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 6 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 5 | 2 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 2 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 6 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 4 | 5 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 3 | 3 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3 | Type 1 | 1 Participants |
Primary
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time frame: Up to 30 days in Cohort 2
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any SAE | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any non-SAE | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any non-SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any non-SAE | 3 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2 | Any non-SAE | 1 Participants |
Primary
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time frame: Up to 30 days in Cohort 3
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any SAE | 0 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any non-SAE | 2 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any non-SAE | 3 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3 | Any non-SAE | 1 Participants |
Primary
Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time frame: Up to 64 days in Cohort 1
Population: Safety Population comprised of all randomized participants who received at least one dose of study medication and was based on the actual treatment received, if this differed from that to which the participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any non-SAE | 3 Participants |
| Part A: Cohort 1: Placebo | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any non-SAE | 5 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any SAE | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any non-SAE | 3 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any non-SAE | 2 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 | Any non-SAE | 2 Participants |
Primary
Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including t1/2 following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 5.54 Hours | Geometric Coefficient of Variation 83.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 7.83 Hours | Geometric Coefficient of Variation 65.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 17.1 Hours | Geometric Coefficient of Variation 32.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 17.0 Hours | Geometric Coefficient of Variation 11.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 19.2 Hours | Geometric Coefficient of Variation 33.7 |
| Part B: GSK3352589 200 mg BID | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 20.5 Hours | Geometric Coefficient of Variation 19.7 |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 16.1 Hours | Geometric Coefficient of Variation 58.9 |
| Cohort 3: GSK3352589 400 mg | Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589 | 14.4 Hours | Geometric Coefficient of Variation 39.7 |
Primary
Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Population: Pharmacokinetic Parameter Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Cohort 1: Placebo | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.25 Hours |
| Part A: Cohort 1: GSK3352589 2 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.50 Hours |
| Part A: Cohort 1: GSK3352589 5 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.00 Hours |
| Part A: Cohort 1: GSK3352589 15 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.50 Hours |
| Part A: Cohort 1: GSK3352589 50 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.25 Hours |
| Part B: GSK3352589 200 mg BID | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 0.750 Hours |
| Part A:Cohort 3: GSK3352589 400 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.25 Hours |
| Cohort 3: GSK3352589 400 mg | Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589 | 1.00 Hours |
Primary
Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-24) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 1.389 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 58.6 |
| Part A: Cohort 1: Placebo | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.988 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 62.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 1.641 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 51.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.970 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 44.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 7.285 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 40.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 9.383 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 23.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 15.73 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 33.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 11.41 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 65.5 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 12.31 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 73.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 24.11 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 45.9 |
Primary
Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.5028 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 87.9 |
| Part A: Cohort 1: Placebo | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.8303 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 82.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.5468 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 72.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.8417 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 53.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 2.522 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 43.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 4.421 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 22.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 7.242 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 34.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 4.055 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 80 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 3.673 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 81.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 9.914 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 54.3 |
Primary
Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.7147 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 84.9 |
| Part A: Cohort 1: Placebo | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.4479 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 89.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.7176 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 53.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.4647 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 75.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 3.763 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 21.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 2.167 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 41.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 3.459 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 84.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 6.121 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 35 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 8.061 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 53.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 2.934 Hour*Nanogram per milliliter | Geometric Coefficient of Variation 90 |
Primary
Part B: Average BSFS at Indicated Time Points
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time frame: Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
Population: Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 4.14 Units on a scale | Standard Deviation 0.99 |
| Part A: Cohort 1: Placebo | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.93 Units on a scale | Standard Deviation 1.14 |
| Part A: Cohort 1: Placebo | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 3.17 Units on a scale | Standard Deviation 1.3 |
| Part A: Cohort 1: Placebo | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 4.12 Units on a scale | Standard Deviation 0.97 |
| Part A: Cohort 1: Placebo | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 4.32 Units on a scale | Standard Deviation 1.14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.55 Units on a scale | Standard Deviation 1.57 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 3.75 Units on a scale | Standard Deviation 1.36 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 3.88 Units on a scale | Standard Deviation 0.63 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 3.63 Units on a scale | Standard Deviation 1.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 3.78 Units on a scale | Standard Deviation 1.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.97 Units on a scale | Standard Deviation 1.06 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 3.77 Units on a scale | Standard Deviation 0.86 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 3.93 Units on a scale | Standard Deviation 0.77 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 3.68 Units on a scale | Standard Deviation 1.14 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 3.92 Units on a scale | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 3.37 Units on a scale | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 3.92 Units on a scale | Standard Deviation 1.43 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.62 Units on a scale | Standard Deviation 0.71 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 3.48 Units on a scale | Standard Deviation 0.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 3.10 Units on a scale | Standard Deviation 0.63 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 3.78 Units on a scale | Standard Deviation 1.08 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 4.13 Units on a scale | Standard Deviation 1.03 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 3.63 Units on a scale | Standard Deviation 1.29 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.75 Units on a scale | Standard Deviation 1.33 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 3.85 Units on a scale | Standard Deviation 0.95 |
| Part B: GSK3352589 200 mg BID | Part B: Average BSFS at Indicated Time Points | Day -1; n=7,4, 6,6,4,5 | 4.30 Units on a scale | Standard Deviation 0.84 |
| Part B: GSK3352589 200 mg BID | Part B: Average BSFS at Indicated Time Points | Days 1-7;n=10,6,6,6,6,6 | 3.38 Units on a scale | Standard Deviation 0.34 |
| Part B: GSK3352589 200 mg BID | Part B: Average BSFS at Indicated Time Points | Days 1-3; n=10,6,6,6,6,6 | 3.37 Units on a scale | Standard Deviation 0.91 |
| Part B: GSK3352589 200 mg BID | Part B: Average BSFS at Indicated Time Points | Days 8-14;n=10,6,6,6,6,6 | 3.48 Units on a scale | Standard Deviation 0.48 |
| Part B: GSK3352589 200 mg BID | Part B: Average BSFS at Indicated Time Points | Days 4-7;n=9,6,6,6,6,6 | 3.45 Units on a scale | Standard Deviation 0.34 |
Primary
Part B: Change From Baseline in Albumin, Total Protein
Blood samples were collected for analysis of hematology parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -2.5 Grams per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | -2.2 Grams per liter | Standard Deviation 2.6 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | -0.7 Grams per liter | Standard Deviation 2.5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -3.0 Grams per liter | Standard Deviation 3.2 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | -2.9 Grams per liter | Standard Deviation 3.7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | -1.4 Grams per liter | Standard Deviation 4.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | -0.4 Grams per liter | Standard Deviation 2.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -2.5 Grams per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | 0.8 Grams per liter | Standard Deviation 4.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -2.3 Grams per liter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | -0.3 Grams per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | 0.2 Grams per liter | Standard Deviation 4.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | 0.5 Grams per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | -0.3 Grams per liter | Standard Deviation 3.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -4.0 Grams per liter | Standard Deviation 2.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | 1.2 Grams per liter | Standard Deviation 1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -2.2 Grams per liter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | 0.2 Grams per liter | Standard Deviation 1.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -1.8 Grams per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | -2.5 Grams per liter | Standard Deviation 2.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | 0.2 Grams per liter | Standard Deviation 3.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | 2.0 Grams per liter | Standard Deviation 4.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | -1.3 Grams per liter | Standard Deviation 3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -3.3 Grams per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -3.7 Grams per liter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | -1.0 Grams per liter | Standard Deviation 2.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | -0.7 Grams per liter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | -1.7 Grams per liter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -4.5 Grams per liter | Standard Deviation 2.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | -2.2 Grams per liter | Standard Deviation 2.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 7; n=10,6,6,6,6,6 | -1.2 Grams per liter | Standard Deviation 4.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Follow-up (Day 25);n=10,6,6,6,6,6 | -0.5 Grams per liter | Standard Deviation 2.9 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Total Protein; Day 15; n=10,5,6,6,6,6 | 0.2 Grams per liter | Standard Deviation 5.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Total Protein;Follow-up (Day 25); n=10,6,6,6,6,6 | -1.3 Grams per liter | Standard Deviation 4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 15; n=10,5,6,6,6,6 | -1.0 Grams per liter | Standard Deviation 3.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Albumin, Total Protein | Albumin; Day 7; n=10,6,6,6,6,6 | -0.8 Grams per liter | Standard Deviation 3.1 |
Primary
Part B: Change From Baseline in ALT, AST and Alk Phos
Blood samples were collected for analysis of hematology parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | -4.8 Units per liter | Standard Deviation 10.9 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | 0.5 Units per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 2.8 Units per liter | Standard Deviation 18.5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | -4.3 Units per liter | Standard Deviation 5.9 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -1.3 Units per liter | Standard Deviation 11.9 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | -3.5 Units per liter | Standard Deviation 8 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -6.7 Units per liter | Standard Deviation 4.4 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.4 Units per liter | Standard Deviation 4 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | -5.3 Units per liter | Standard Deviation 9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.2 Units per liter | Standard Deviation 5.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -8.2 Units per liter | Standard Deviation 4.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 0.3 Units per liter | Standard Deviation 4.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | -7.8 Units per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | -7.7 Units per liter | Standard Deviation 5.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | -7.8 Units per liter | Standard Deviation 17.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | -1.4 Units per liter | Standard Deviation 3.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | -1.6 Units per liter | Standard Deviation 4.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -7.3 Units per liter | Standard Deviation 9.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | -6.2 Units per liter | Standard Deviation 8.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | -6.2 Units per liter | Standard Deviation 6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -5.3 Units per liter | Standard Deviation 8.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | -9.3 Units per liter | Standard Deviation 7.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 3.5 Units per liter | Standard Deviation 7.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | 3.2 Units per liter | Standard Deviation 6.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | 1.7 Units per liter | Standard Deviation 5.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -8.7 Units per liter | Standard Deviation 4.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | -5.3 Units per liter | Standard Deviation 6.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | 7.7 Units per liter | Standard Deviation 16 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | 1.2 Units per liter | Standard Deviation 12.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.0 Units per liter | Standard Deviation 6.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -3.8 Units per liter | Standard Deviation 6.7 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | 0.5 Units per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 7.7 Units per liter | Standard Deviation 6.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -2.8 Units per liter | Standard Deviation 6.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | -0.5 Units per liter | Standard Deviation 7.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | 2.3 Units per liter | Standard Deviation 5.5 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -0.7 Units per liter | Standard Deviation 4.1 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | -0.8 Units per liter | Standard Deviation 2.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | -4.8 Units per liter | Standard Deviation 6.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 3.0 Units per liter | Standard Deviation 10.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.3 Units per liter | Standard Deviation 7.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | 1.2 Units per liter | Standard Deviation 4.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.7 Units per liter | Standard Deviation 7.1 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -10.5 Units per liter | Standard Deviation 5.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | -0.8 Units per liter | Standard Deviation 2.8 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | AST ; Day 7; n=10,6,6,6,6,6 | 0.7 Units per liter | Standard Deviation 3.6 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Day 15; n=10,5,6,6,6,6 | 0.7 Units per liter | Standard Deviation 6.7 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Day 15; n=10,5,6,6,6,6 | -0.3 Units per liter | Standard Deviation 3.9 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 15; n=10,5,6,6,6,6 | -0.8 Units per liter | Standard Deviation 3.8 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos ; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.7 Units per liter | Standard Deviation 3 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | AST; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.2 Units per liter | Standard Deviation 4.6 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Day 7; n=10,6,6,6,6,6 | -0.3 Units per liter | Standard Deviation 2.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | Alk Phos; Day 7; n=10,6,6,6,6,6 | -1.8 Units per liter | Standard Deviation 6.1 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in ALT, AST and Alk Phos | ALT; Follow-up (Day 25); n=10,6,6,6,6,6 | -2.3 Units per liter | Standard Deviation 3.3 |
Primary
Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | -0.09 10^9 cells per liter | Standard Deviation 0.11 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | 0.04 10^9 cells per liter | Standard Deviation 0.32 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.31 10^9 cells per liter | Standard Deviation 0.74 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.1 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | -0.08 10^9 cells per liter | Standard Deviation 1.05 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | -0.09 10^9 cells per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 17.5 10^9 cells per liter | Standard Deviation 34.5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -0.18 10^9 cells per liter | Standard Deviation 1.13 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.01 10^9 cells per liter | Standard Deviation 0.09 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.04 10^9 cells per liter | Standard Deviation 0.12 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | 10.4 10^9 cells per liter | Standard Deviation 25 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.55 10^9 cells per liter | Standard Deviation 0.94 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.14 10^9 cells per liter | Standard Deviation 0.25 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | 12.3 10^9 cells per liter | Standard Deviation 28.5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | -0.03 10^9 cells per liter | Standard Deviation 0.09 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | -0.32 10^9 cells per liter | Standard Deviation 0.79 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | 0.01 10^9 cells per liter | Standard Deviation 0.09 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.39 10^9 cells per liter | Standard Deviation 0.72 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | -0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.05 10^9 cells per liter | Standard Deviation 0.1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.02 10^9 cells per liter | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.57 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.00 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | 0.10 10^9 cells per liter | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.00 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -0.32 10^9 cells per liter | Standard Deviation 0.52 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | 0.04 10^9 cells per liter | Standard Deviation 0.11 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.09 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 37.3 10^9 cells per liter | Standard Deviation 24.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | -0.35 10^9 cells per liter | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | 24.2 10^9 cells per liter | Standard Deviation 26.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.22 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.12 10^9 cells per liter | Standard Deviation 0.33 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.04 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | 9.7 10^9 cells per liter | Standard Deviation 21.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.12 10^9 cells per liter | Standard Deviation 0.59 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.42 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | -0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -0.65 10^9 cells per liter | Standard Deviation 0.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | -0.08 10^9 cells per liter | Standard Deviation 0.12 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | 0.10 10^9 cells per liter | Standard Deviation 0.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | -0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | -0.13 10^9 cells per liter | Standard Deviation 0.76 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | 8.3 10^9 cells per liter | Standard Deviation 20.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.06 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.25 10^9 cells per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.07 10^9 cells per liter | Standard Deviation 0.66 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | -0.02 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.04 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 26.2 10^9 cells per liter | Standard Deviation 24.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | -0.42 10^9 cells per liter | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | -0.18 10^9 cells per liter | Standard Deviation 0.24 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.43 10^9 cells per liter | Standard Deviation 0.88 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | -3.0 10^9 cells per liter | Standard Deviation 23.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.22 10^9 cells per liter | Standard Deviation 0.77 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | -0.10 10^9 cells per liter | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | -0.05 10^9 cells per liter | Standard Deviation 0.36 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.00 10^9 cells per liter | Standard Deviation 0.13 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | -0.10 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | -0.10 10^9 cells per liter | Standard Deviation 0.09 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.10 10^9 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | -0.65 10^9 cells per liter | Standard Deviation 0.98 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.72 10^9 cells per liter | Standard Deviation 0.87 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.37 10^9 cells per liter | Standard Deviation 1.33 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | 26.7 10^9 cells per liter | Standard Deviation 12.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | 3.7 10^9 cells per liter | Standard Deviation 16.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 27.3 10^9 cells per liter | Standard Deviation 37 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -0.82 10^9 cells per liter | Standard Deviation 1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | -0.82 10^9 cells per liter | Standard Deviation 0.85 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.45 10^9 cells per liter | Standard Deviation 1.24 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.1 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.73 10^9 cells per liter | Standard Deviation 3.34 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.07 10^9 cells per liter | Standard Deviation 0.23 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | -11.0 10^9 cells per liter | Standard Deviation 12.1 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | 0.40 10^9 cells per liter | Standard Deviation 0.25 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | 0.23 10^9 cells per liter | Standard Deviation 0.19 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.03 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | 7.3 10^9 cells per liter | Standard Deviation 25.5 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 2.5 10^9 cells per liter | Standard Deviation 20.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | 0.05 10^9 cells per liter | Standard Deviation 0.05 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -0.53 10^9 cells per liter | Standard Deviation 0.92 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.07 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.98 10^9 cells per liter | Standard Deviation 3.38 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | -0.82 10^9 cells per liter | Standard Deviation 0.79 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | 0.17 10^9 cells per liter | Standard Deviation 0.27 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | -0.08 10^9 cells per liter | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.58 10^9 cells per liter | Standard Deviation 0.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 7;n=10, 6,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 7;n=10, 6,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.08 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 7;n=10, 6,6,6,6,6 | -0.88 10^9 cells per liter | Standard Deviation 0.57 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes ;Day 15;n=10, 5,6,6,6,6 | -1.10 10^9 cells per liter | Standard Deviation 0.62 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 | 2.5 10^9 cells per liter | Standard Deviation 9 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.58 10^9 cells per liter | Standard Deviation 1.05 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.32 10^9 cells per liter | Standard Deviation 0.17 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.07 10^9 cells per liter | Standard Deviation 0.1 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 15; n=10, 5,6,6,6,6 | -0.10 10^9 cells per liter | Standard Deviation 0.19 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Day 15;n=10, 5,6,6,6,6 | 0.02 10^9 cells per liter | Standard Deviation 0.04 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Day 7;n=10, 6,6,6,6,6 | 0.04 10^9 cells per liter | Standard Deviation 0.08 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 7;n=10, 6,6,6,6,6 | 4.5 10^9 cells per liter | Standard Deviation 21.1 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Neutrophils; Day 15;n=10, 5,6,6,6,6 | -0.95 10^9 cells per liter | Standard Deviation 0.75 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 | -0.22 10^9 cells per liter | Standard Deviation 0.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 | -1.00 10^9 cells per liter | Standard Deviation 1.01 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Monocytes; Day 15;n=10, 5,6,6,6,6 | -0.07 10^9 cells per liter | Standard Deviation 0.08 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Leukocytes; Day 7;n=10, 6,6,6,6,6 | -1.08 10^9 cells per liter | Standard Deviation 0.67 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Platelets; Day 15;n=10, 5,6,6,6,6 | 7.5 10^9 cells per liter | Standard Deviation 21.3 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 | -0.03 10^9 cells per liter | Standard Deviation 0.11 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 | 0.00 10^9 cells per liter | Standard Deviation 0 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes | Eosinophils, Day 15;n=10, 5,6,6,6,6 | -0.03 10^9 cells per liter | Standard Deviation 0.08 |
Primary
Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected for analysis of hematology parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 1.00 Micromoles per liter | Standard Deviation 0.67 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | 1.06 Micromoles per liter | Standard Deviation 0.62 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 1.2 Micromoles per liter | Standard Deviation 1.6 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | 3.4 Micromoles per liter | Standard Deviation 6.9 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 1.31 Micromoles per liter | Standard Deviation 0.43 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | -3.0 Micromoles per liter | Standard Deviation 5.3 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 1.9 Micromoles per liter | Standard Deviation 2 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 2.4 Micromoles per liter | Standard Deviation 1.7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | 0.2 Micromoles per liter | Standard Deviation 6.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | 1.10 Micromoles per liter | Standard Deviation 1.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.0 Micromoles per liter | Standard Deviation 16.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 1.0 Micromoles per liter | Standard Deviation 2.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 0.5 Micromoles per liter | Standard Deviation 4.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 2.5 Micromoles per liter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 1.10 Micromoles per liter | Standard Deviation 0.54 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | -5.5 Micromoles per liter | Standard Deviation 14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 1.30 Micromoles per liter | Standard Deviation 0.59 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | 2.2 Micromoles per liter | Standard Deviation 12.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 2.5 Micromoles per liter | Standard Deviation 1.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.8 Micromoles per liter | Standard Deviation 15 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | -1.3 Micromoles per liter | Standard Deviation 15.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 0.73 Micromoles per liter | Standard Deviation 0.81 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | 0.95 Micromoles per liter | Standard Deviation 0.87 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 2.5 Micromoles per liter | Standard Deviation 2.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 1.32 Micromoles per liter | Standard Deviation 1.22 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | -1.0 Micromoles per liter | Standard Deviation 15.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 3.2 Micromoles per liter | Standard Deviation 2.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.5 Micromoles per liter | Standard Deviation 7.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 2.0 Micromoles per liter | Standard Deviation 1.7 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 1.5 Micromoles per liter | Standard Deviation 1.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 1.8 Micromoles per liter | Standard Deviation 3.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | -3.3 Micromoles per liter | Standard Deviation 7.3 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | -1.0 Micromoles per liter | Standard Deviation 7.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 1.22 Micromoles per liter | Standard Deviation 0.64 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 1.73 Micromoles per liter | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | 1.78 Micromoles per liter | Standard Deviation 1.06 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | -9.2 Micromoles per liter | Standard Deviation 13.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | -13.0 Micromoles per liter | Standard Deviation 9.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 0.48 Micromoles per liter | Standard Deviation 1.15 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 0.3 Micromoles per liter | Standard Deviation 4.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | -0.12 Micromoles per liter | Standard Deviation 1.42 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 0.73 Micromoles per liter | Standard Deviation 1.17 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 2.3 Micromoles per liter | Standard Deviation 2.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 2.0 Micromoles per liter | Standard Deviation 2.8 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | -4.0 Micromoles per liter | Standard Deviation 11.3 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 7; n=10,6,6,6,6,6 | 2.5 Micromoles per liter | Standard Deviation 4.2 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine ; Day 7; n=10,6,6,6,6,6 | -1.0 Micromoles per liter | Standard Deviation 6.7 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.3 Micromoles per liter | Standard Deviation 5.2 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin; Follow-up(Day 25);n=10,6,6,6,6,6 | 0.48 Micromoles per liter | Standard Deviation 1.23 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 15; n=10,5,6,6,6,6 | 0.25 Micromoles per liter | Standard Deviation 1.51 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Direct bilirubin ; Day 7; n=10,6,6,6,6,6 | 0.63 Micromoles per liter | Standard Deviation 1.53 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Follow-up (Day 25);n=10,6,6,6,6,6 | 0.8 Micromoles per liter | Standard Deviation 3.8 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Creatinine; Day 15; n=10,5,6,6,6,6 | -2.7 Micromoles per liter | Standard Deviation 4.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin | Bilirubin; Day 15; n=10,5,6,6,6,6 | 2.0 Micromoles per liter | Standard Deviation 3.4 |
Primary
Part B: Change From Baseline in Body Temperature
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | 0.09 Celsius | Standard Deviation 0.55 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | -0.04 Celsius | Standard Deviation 0.67 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | 0.17 Celsius | Standard Deviation 0.51 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | 0.16 Celsius | Standard Deviation 0.32 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | 0.07 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.17 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.18 Celsius | Standard Deviation 0.58 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | -0.07 Celsius | Standard Deviation 0.42 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.32 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | -0.07 Celsius | Standard Deviation 0.51 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | 0.08 Celsius | Standard Deviation 0.4 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | 0.17 Celsius | Standard Deviation 0.34 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.17 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | -0.05 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.27 Celsius | Standard Deviation 0.35 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.18 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.18 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | 0.17 Celsius | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | -0.03 Celsius | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | 0.03 Celsius | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.48 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | -0.10 Celsius | Standard Deviation 0.15 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | -0.10 Celsius | Standard Deviation 0.36 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | 0.18 Celsius | Standard Deviation 0.13 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | 0.33 Celsius | Standard Deviation 0.28 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.12 Celsius | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.10 Celsius | Standard Deviation 0.24 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.12 Celsius | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | -0.02 Celsius | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | 0.15 Celsius | Standard Deviation 0.32 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.42 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.17 Celsius | Standard Deviation 0.52 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.27 Celsius | Standard Deviation 0.44 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.08 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.47 Celsius | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | -0.23 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | 0.30 Celsius | Standard Deviation 0.23 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.27 Celsius | Standard Deviation 0.44 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | 0.08 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | 0.23 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | -0.07 Celsius | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.08 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | 0.15 Celsius | Standard Deviation 0.48 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | 0.40 Celsius | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | -0.02 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | -0.05 Celsius | Standard Deviation 0.48 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.24 Celsius | Standard Deviation 0.61 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | 0.53 Celsius | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | -0.02 Celsius | Standard Deviation 0.43 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.23 Celsius | Standard Deviation 0.18 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | -0.10 Celsius | Standard Deviation 0.49 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | 0.07 Celsius | Standard Deviation 0.42 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.23 Celsius | Standard Deviation 0.18 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.25 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | 0.55 Celsius | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | 0.08 Celsius | Standard Deviation 0.56 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.25 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | -0.08 Celsius | Standard Deviation 0.18 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | 0.15 Celsius | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.68 Celsius | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | 0.45 Celsius | Standard Deviation 0.33 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.30 Celsius | Standard Deviation 0.55 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -0.10 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | 0.13 Celsius | Standard Deviation 0.52 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | 0.27 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | 0.13 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | 0.07 Celsius | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | 0.13 Celsius | Standard Deviation 0.57 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.02 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.02 Celsius | Standard Deviation 0.29 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | 0.02 Celsius | Standard Deviation 0.54 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | 0.23 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | -0.48 Celsius | Standard Deviation 0.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0.5 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | -0.07 Celsius | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | -0.10 Celsius | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.28 Celsius | Standard Deviation 0.47 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.47 Celsius | Standard Deviation 0.32 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 12; n=10,6,6,6,6,6 | -0.08 Celsius | Standard Deviation 0.41 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 11; n=10,6,6,6,6,6 | -0.02 Celsius | Standard Deviation 0.39 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 10; n=10,6,6,6,6,6 | -0.02 Celsius | Standard Deviation 0.32 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 8; n=10,6,6,6,6,6 | -0.15 Celsius | Standard Deviation 0.61 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 2; n=10,6,6,6,6,6 | -0.20 Celsius | Standard Deviation 0.39 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -0.12 Celsius | Standard Deviation 0.48 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -0.08 Celsius | Standard Deviation 0.42 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 7, Pre-dose; n=10,6,6,6,6,6 | -0.08 Celsius | Standard Deviation 0.42 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 6; n=10,6,6,6,6,6 | 0.05 Celsius | Standard Deviation 0.49 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 5; n=10,6,6,6,6,6 | -0.45 Celsius | Standard Deviation 0.38 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Follow-up (Day 25); n=10,6,5,6,6,6 | 0.08 Celsius | Standard Deviation 0.36 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 15; n=10,5,6,6,6,6 | 0.03 Celsius | Standard Deviation 0.31 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 4; n=10,6,6,6,6,6 | 0.03 Celsius | Standard Deviation 0.36 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 0.00 Celsius | Standard Deviation 0 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 9; n=10,6,6,6,6,6 | -0.20 Celsius | Standard Deviation 0.62 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 13; n=10,6,6,6,6,6 | -0.12 Celsius | Standard Deviation 0.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 3; n=10,6,6,6,6,6 | 0.03 Celsius | Standard Deviation 0.42 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Body Temperature | Day 14, Pre-dose; n=10,6,6,6,6,6 | -0.12 Celsius | Standard Deviation 0.48 |
Primary
Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea
Blood samples were collected for analysis of hematology parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | -0.001 Millimoles per liter | Standard Deviation 0.086 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.16 Millimoles per liter | Standard Deviation 0.8 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.049 Millimoles per liter | Standard Deviation 0.177 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | 0.026 Millimoles per liter | Standard Deviation 0.142 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -1.56 Millimoles per liter | Standard Deviation 1.04 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -0.84 Millimoles per liter | Standard Deviation 0.88 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | -1.8 Millimoles per liter | Standard Deviation 2.7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -1.8 Millimoles per liter | Standard Deviation 2.7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.04 Millimoles per liter | Standard Deviation 0.41 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.48 Millimoles per liter | Standard Deviation 1.04 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.6 Millimoles per liter | Standard Deviation 2.8 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | -0.06 Millimoles per liter | Standard Deviation 0.33 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | 0.22 Millimoles per liter | Standard Deviation 0.64 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.21 Millimoles per liter | Standard Deviation 0.96 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -0.37 Millimoles per liter | Standard Deviation 0.81 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -0.52 Millimoles per liter | Standard Deviation 0.75 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -0.88 Millimoles per liter | Standard Deviation 0.79 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.50 Millimoles per liter | Standard Deviation 1.69 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.160 Millimoles per liter | Standard Deviation 0.067 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.78 Millimoles per liter | Standard Deviation 0.69 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -0.70 Millimoles per liter | Standard Deviation 0.62 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | 0.040 Millimoles per liter | Standard Deviation 0.065 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.03 Millimoles per liter | Standard Deviation 1 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | -0.17 Millimoles per liter | Standard Deviation 0.39 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.03 Millimoles per liter | Standard Deviation 0.43 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -2.7 Millimoles per liter | Standard Deviation 2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | -0.06 Millimoles per liter | Standard Deviation 0.54 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | -2.0 Millimoles per liter | Standard Deviation 2.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | -2.3 Millimoles per liter | Standard Deviation 2.4 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | 0.124 Millimoles per liter | Standard Deviation 0.093 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.157 Millimoles per liter | Standard Deviation 0.061 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.27 Millimoles per liter | Standard Deviation 0.91 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | 0.47 Millimoles per liter | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.30 Millimoles per liter | Standard Deviation 0.67 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -2.58 Millimoles per liter | Standard Deviation 2.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -2.82 Millimoles per liter | Standard Deviation 2.01 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -0.17 Millimoles per liter | Standard Deviation 0.52 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.5 Millimoles per liter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.23 Millimoles per liter | Standard Deviation 0.23 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | 0.108 Millimoles per liter | Standard Deviation 0.027 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.05 Millimoles per liter | Standard Deviation 0.45 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | 0.167 Millimoles per liter | Standard Deviation 0.044 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | 0.38 Millimoles per liter | Standard Deviation 0.42 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -0.3 Millimoles per liter | Standard Deviation 1.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | -0.5 Millimoles per liter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | 1.0 Millimoles per liter | Standard Deviation 2.7 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -0.72 Millimoles per liter | Standard Deviation 0.35 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.08 Millimoles per liter | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.40 Millimoles per liter | Standard Deviation 1.39 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -0.43 Millimoles per liter | Standard Deviation 0.42 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | 0.57 Millimoles per liter | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | 0.050 Millimoles per liter | Standard Deviation 0.055 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | 0.18 Millimoles per liter | Standard Deviation 0.15 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | 0.073 Millimoles per liter | Standard Deviation 0.026 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.07 Millimoles per liter | Standard Deviation 0.41 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -1.17 Millimoles per liter | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.8 Millimoles per liter | Standard Deviation 2.2 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -0.8 Millimoles per liter | Standard Deviation 2.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.100 Millimoles per liter | Standard Deviation 0.059 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.17 Millimoles per liter | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.7 Millimoles per liter | Standard Deviation 3.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | -0.045 Millimoles per liter | Standard Deviation 0.106 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | -0.02 Millimoles per liter | Standard Deviation 0.31 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | 0.15 Millimoles per liter | Standard Deviation 0.74 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -1.18 Millimoles per liter | Standard Deviation 1.28 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | 0.052 Millimoles per liter | Standard Deviation 0.098 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.023 Millimoles per liter | Standard Deviation 0.08 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -1.40 Millimoles per liter | Standard Deviation 1.21 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.10 Millimoles per liter | Standard Deviation 1.67 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | 1.8 Millimoles per liter | Standard Deviation 3.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.10 Millimoles per liter | Standard Deviation 0.32 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -1.02 Millimoles per liter | Standard Deviation 0.55 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.08 Millimoles per liter | Standard Deviation 1.21 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.47 Millimoles per liter | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -2.3 Millimoles per liter | Standard Deviation 3 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.03 Millimoles per liter | Standard Deviation 1.03 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.00 Millimoles per liter | Standard Deviation 0.28 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 7; n=10,6,6,6,6,6 | -0.035 Millimoles per liter | Standard Deviation 0.1 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Day 15; n=10,5,6,6,6,6 | -0.032 Millimoles per liter | Standard Deviation 0.138 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Calcium; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.005 Millimoles per liter | Standard Deviation 0.099 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 7; n=10,6,6,6,6,6 | -0.33 Millimoles per liter | Standard Deviation 0.47 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Day 15; n=10,5,6,6,6,6 | -0.40 Millimoles per liter | Standard Deviation 0.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Glucose; Follow-up (Day 25); n=10,6,6,6,6,6 | -0.12 Millimoles per liter | Standard Deviation 0.98 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 7; n=10,6,6,6,6,6 | -0.05 Millimoles per liter | Standard Deviation 0.23 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Potassium; Day 15; n=10,5,6,6,6,6 | 0.07 Millimoles per liter | Standard Deviation 0.36 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 7; n=10,6,6,6,6,6 | -0.3 Millimoles per liter | Standard Deviation 2.1 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Day 15; n=10,5,6,6,6,6 | 0.3 Millimoles per liter | Standard Deviation 2.3 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Sodium; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.2 Millimoles per liter | Standard Deviation 0.8 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 7; n=10,6,6,6,6,6 | -0.20 Millimoles per liter | Standard Deviation 0.75 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea | Urea; Day 15; n=10,5,6,6,6,6 | -1.25 Millimoles per liter | Standard Deviation 0.78 |
Primary
Part B: Change From Baseline in Erythrocyte MCH
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.72 Picogram | Standard Deviation 0.57 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | -0.77 Picogram | Standard Deviation 0.72 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | -0.87 Picogram | Standard Deviation 0.55 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | -0.87 Picogram | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | -0.70 Picogram | Standard Deviation 0.37 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.78 Picogram | Standard Deviation 0.58 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | -1.30 Picogram | Standard Deviation 0.25 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | -1.25 Picogram | Standard Deviation 0.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | -1.33 Picogram | Standard Deviation 0.14 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | -0.95 Picogram | Standard Deviation 0.38 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | -1.13 Picogram | Standard Deviation 0.21 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.98 Picogram | Standard Deviation 0.26 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | -0.28 Picogram | Standard Deviation 0.34 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | -0.50 Picogram | Standard Deviation 0.46 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.47 Picogram | Standard Deviation 0.39 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCH | Day 7; n=10,6,6,6,6,6 | 0.13 Picogram | Standard Deviation 0.85 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCH | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.77 Picogram | Standard Deviation 0.54 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCH | Day 15; n=10,5,6,6,6,6 | 0.23 Picogram | Standard Deviation 0.81 |
Primary
Part B: Change From Baseline in Erythrocyte MCV
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | -1.0 Femtoliter | Standard Deviation 1.2 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | -1.4 Femtoliter | Standard Deviation 1.6 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.5 Femtoliter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | 0.2 Femtoliter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | 0.2 Femtoliter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.0 Femtoliter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | -2.2 Femtoliter | Standard Deviation 1.7 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | -2.7 Femtoliter | Standard Deviation 1.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | -1.5 Femtoliter | Standard Deviation 1.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.3 Femtoliter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | -0.2 Femtoliter | Standard Deviation 0.8 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | -0.3 Femtoliter | Standard Deviation 1.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | 0.8 Femtoliter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | 0.2 Femtoliter | Standard Deviation 1.2 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | 1.8 Femtoliter | Standard Deviation 0.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCV | Day 15; n=10,5,6,6,6,6 | -0.8 Femtoliter | Standard Deviation 1.9 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCV | Day 7; n=10,6,6,6,6,6 | -1.3 Femtoliter | Standard Deviation 1.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocyte MCV | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.0 Femtoliter | Standard Deviation 0.9 |
Primary
Part B: Change From Baseline in Erythrocytes
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.175 10^12 cells per liter | Standard Deviation 0.258 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | 0.081 10^12 cells per liter | Standard Deviation 0.25 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.075 10^12 cells per liter | Standard Deviation 0.355 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.334 10^12 cells per liter | Standard Deviation 0.235 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | 0.208 10^12 cells per liter | Standard Deviation 0.119 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.287 10^12 cells per liter | Standard Deviation 0.256 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.270 10^12 cells per liter | Standard Deviation 0.19 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | 0.033 10^12 cells per liter | Standard Deviation 0.06 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.155 10^12 cells per liter | Standard Deviation 0.182 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.302 10^12 cells per liter | Standard Deviation 0.179 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | 0.230 10^12 cells per liter | Standard Deviation 0.145 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.158 10^12 cells per liter | Standard Deviation 0.239 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.162 10^12 cells per liter | Standard Deviation 0.252 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | -0.183 10^12 cells per liter | Standard Deviation 0.183 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.195 10^12 cells per liter | Standard Deviation 0.165 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocytes | Day 7; n=10,6,6,6,6,6 | -0.023 10^12 cells per liter | Standard Deviation 0.251 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocytes | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.227 10^12 cells per liter | Standard Deviation 0.157 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Erythrocytes | Day 15; n=10,5,6,6,6,6 | 0.082 10^12 cells per liter | Standard Deviation 0.275 |
Primary
Part B: Change From Baseline in Hematocrit
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.009 Proportion of red blood cells in blood | Standard Deviation 0.025 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | 0.000 Proportion of red blood cells in blood | Standard Deviation 0.029 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.005 Proportion of red blood cells in blood | Standard Deviation 0.032 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.030 Proportion of red blood cells in blood | Standard Deviation 0.025 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | 0.018 Proportion of red blood cells in blood | Standard Deviation 0.01 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.025 Proportion of red blood cells in blood | Standard Deviation 0.021 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.015 Proportion of red blood cells in blood | Standard Deviation 0.018 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | -0.012 Proportion of red blood cells in blood | Standard Deviation 0.012 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.005 Proportion of red blood cells in blood | Standard Deviation 0.016 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.025 Proportion of red blood cells in blood | Standard Deviation 0.016 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | 0.018 Proportion of red blood cells in blood | Standard Deviation 0.013 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.017 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.017 Proportion of red blood cells in blood | Standard Deviation 0.019 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | -0.017 Proportion of red blood cells in blood | Standard Deviation 0.014 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.008 Proportion of red blood cells in blood | Standard Deviation 0.015 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hematocrit | Day 7; n=10,6,6,6,6,6 | -0.007 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hematocrit | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.020 Proportion of red blood cells in blood | Standard Deviation 0.017 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hematocrit | Day 15; n=10,5,6,6,6,6 | 0.005 Proportion of red blood cells in blood | Standard Deviation 0.026 |
Primary
Part B: Change From Baseline in Hemoglobin
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 1.4 Grams per liter | Standard Deviation 8.7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | -1.3 Grams per liter | Standard Deviation 10.4 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | -1.8 Grams per liter | Standard Deviation 6.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 6.4 Grams per liter | Standard Deviation 6.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | 1.8 Grams per liter | Standard Deviation 4.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | 4.3 Grams per liter | Standard Deviation 7.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | -1.8 Grams per liter | Standard Deviation 5.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | -5.3 Grams per liter | Standard Deviation 2 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 1.3 Grams per liter | Standard Deviation 5.6 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 3.7 Grams per liter | Standard Deviation 5.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | 0.7 Grams per liter | Standard Deviation 4.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | -0.3 Grams per liter | Standard Deviation 5.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 2.2 Grams per liter | Standard Deviation 4.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | -6.7 Grams per liter | Standard Deviation 4.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | -3.5 Grams per liter | Standard Deviation 4.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hemoglobin | Follow-up (Day 25); n=10,6,6,6,6,6 | -3.0 Grams per liter | Standard Deviation 4.6 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hemoglobin | Day 15; n=10,5,6,6,6,6 | 3.7 Grams per liter | Standard Deviation 6.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Hemoglobin | Day 7; n=10,6,6,6,6,6 | 0.0 Grams per liter | Standard Deviation 6.9 |
Primary
Part B: Change From Baseline in Pulse Rate
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | 3.25 Beats per minute | Standard Deviation 8.47 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 0.85 Beats per minute | Standard Deviation 4.34 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | -0.50 Beats per minute | Standard Deviation 5.33 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 6.03 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.40 Beats per minute | Standard Deviation 5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | -2.35 Beats per minute | Standard Deviation 3.93 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | 3.35 Beats per minute | Standard Deviation 7.07 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 6.25 Beats per minute | Standard Deviation 8.77 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | 2.45 Beats per minute | Standard Deviation 5.83 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | -0.50 Beats per minute | Standard Deviation 5.48 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | 1.45 Beats per minute | Standard Deviation 7.98 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -0.10 Beats per minute | Standard Deviation 5.64 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | 4.85 Beats per minute | Standard Deviation 4.53 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -1.55 Beats per minute | Standard Deviation 4.75 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | 1.05 Beats per minute | Standard Deviation 8.59 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | 0.55 Beats per minute | Standard Deviation 7.37 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 0.20 Beats per minute | Standard Deviation 4.82 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | -1.55 Beats per minute | Standard Deviation 5.23 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | 3.33 Beats per minute | Standard Deviation 7.05 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -0.42 Beats per minute | Standard Deviation 8.65 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | 2.50 Beats per minute | Standard Deviation 10.8 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | 2.42 Beats per minute | Standard Deviation 10.53 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | -1.17 Beats per minute | Standard Deviation 9.03 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | 5.42 Beats per minute | Standard Deviation 11.74 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.25 Beats per minute | Standard Deviation 8.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 3.75 Beats per minute | Standard Deviation 10.14 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | 1.42 Beats per minute | Standard Deviation 9.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | 2.58 Beats per minute | Standard Deviation 7.01 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -1.83 Beats per minute | Standard Deviation 10.52 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | -2.58 Beats per minute | Standard Deviation 10.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | -1.17 Beats per minute | Standard Deviation 12.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | 2.00 Beats per minute | Standard Deviation 9.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.25 Beats per minute | Standard Deviation 10.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.90 Beats per minute | Standard Deviation 11.06 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 4.00 Beats per minute | Standard Deviation 5.28 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 0.00 Beats per minute | Standard Deviation 6.67 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | 0.83 Beats per minute | Standard Deviation 5.91 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -5.08 Beats per minute | Standard Deviation 5.38 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | -2.33 Beats per minute | Standard Deviation 8.68 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -2.25 Beats per minute | Standard Deviation 4.16 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | -1.75 Beats per minute | Standard Deviation 6.33 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | -1.67 Beats per minute | Standard Deviation 3.8 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -4.33 Beats per minute | Standard Deviation 5.82 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | -0.33 Beats per minute | Standard Deviation 8.94 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 4.25 Beats per minute | Standard Deviation 4.41 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 10.24 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | 2.75 Beats per minute | Standard Deviation 6.83 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 6.17 Beats per minute | Standard Deviation 9.68 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | 1.42 Beats per minute | Standard Deviation 6.15 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -5.75 Beats per minute | Standard Deviation 4.26 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | -0.08 Beats per minute | Standard Deviation 8.63 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 5.52 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | 0.58 Beats per minute | Standard Deviation 5.62 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | -1.50 Beats per minute | Standard Deviation 10.11 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | 2.92 Beats per minute | Standard Deviation 11.59 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | -0.75 Beats per minute | Standard Deviation 5.66 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -0.58 Beats per minute | Standard Deviation 5.52 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | 1.08 Beats per minute | Standard Deviation 8.34 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | 2.08 Beats per minute | Standard Deviation 7.28 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 4.00 Beats per minute | Standard Deviation 6.57 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | 2.50 Beats per minute | Standard Deviation 5.59 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 7.62 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | 1.33 Beats per minute | Standard Deviation 9.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | 0.00 Beats per minute | Standard Deviation 6.75 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | 0.50 Beats per minute | Standard Deviation 8.63 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | 0.17 Beats per minute | Standard Deviation 4.69 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | -2.17 Beats per minute | Standard Deviation 7.81 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 10.58 Beats per minute | Standard Deviation 8.44 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -2.58 Beats per minute | Standard Deviation 7.39 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | 1.92 Beats per minute | Standard Deviation 9.09 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | -1.33 Beats per minute | Standard Deviation 8.24 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -3.58 Beats per minute | Standard Deviation 4.9 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | 2.58 Beats per minute | Standard Deviation 9.16 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | -4.42 Beats per minute | Standard Deviation 12.73 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | 1.75 Beats per minute | Standard Deviation 10.11 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | -0.17 Beats per minute | Standard Deviation 10.75 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | -2.25 Beats per minute | Standard Deviation 11.49 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -1.25 Beats per minute | Standard Deviation 7.29 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 5.83 Beats per minute | Standard Deviation 13.14 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.50 Beats per minute | Standard Deviation 9.44 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | -0.17 Beats per minute | Standard Deviation 7.75 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -1.17 Beats per minute | Standard Deviation 7.13 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | -6.92 Beats per minute | Standard Deviation 8.45 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | 0.08 Beats per minute | Standard Deviation 9.04 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 3.83 Beats per minute | Standard Deviation 9.11 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 5.58 Beats per minute | Standard Deviation 8.03 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 9.96 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -3.33 Beats per minute | Standard Deviation 8.3 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | -2.67 Beats per minute | Standard Deviation 7.28 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | 0.42 Beats per minute | Standard Deviation 12.46 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 2; n=10,6,6,6,6,6 | 0.08 Beats per minute | Standard Deviation 6.41 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 9; n=10,6,6,6,6,6 | 2.67 Beats per minute | Standard Deviation 10.35 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 3; n=10,6,6,6,6,6 | -2.25 Beats per minute | Standard Deviation 5.35 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -0.08 Beats per minute | Standard Deviation 6.67 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 5; n=10,6,6,6,6,6 | 3.92 Beats per minute | Standard Deviation 10.11 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 12; n=10,6,6,6,6,6 | 3.25 Beats per minute | Standard Deviation 11.02 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 8; n=10,6,6,6,6,6 | 5.83 Beats per minute | Standard Deviation 6.93 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Follow-up (Day 25); n=10,6,6,6,6,6 | 6.92 Beats per minute | Standard Deviation 6.85 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 10; n=10,6,6,6,6,6 | -2.17 Beats per minute | Standard Deviation 7.82 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | 1.17 Beats per minute | Standard Deviation 6.63 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 4; n=10,6,6,6,6,6 | -0.17 Beats per minute | Standard Deviation 6.77 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 13; n=10,6,6,6,6,6 | -2.08 Beats per minute | Standard Deviation 9.58 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -3.42 Beats per minute | Standard Deviation 5.74 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 11; n=10,6,6,6,6,6 | -3.58 Beats per minute | Standard Deviation 7.01 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 7, Pre-dose; n=10,6,6,6,6,6 | -0.25 Beats per minute | Standard Deviation 5.4 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 6; n=10,6,6,6,6,6 | -2.67 Beats per minute | Standard Deviation 8.05 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 15; n=10,5,6,6,6,6 | 7.67 Beats per minute | Standard Deviation 6.05 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in Pulse Rate | Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.42 Beats per minute | Standard Deviation 4.89 |
Primary
Part B: Change From Baseline in SBP and DBP
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Population: Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -8.55 Millimeters of mercury | Standard Deviation 8.39 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -8.95 Millimeters of mercury | Standard Deviation 5.71 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -7.35 Millimeters of mercury | Standard Deviation 5.61 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -9.00 Millimeters of mercury | Standard Deviation 5.61 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -5.90 Millimeters of mercury | Standard Deviation 6.5 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -6.80 Millimeters of mercury | Standard Deviation 10.14 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -7.25 Millimeters of mercury | Standard Deviation 8.36 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -9.65 Millimeters of mercury | Standard Deviation 6.93 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | -7.75 Millimeters of mercury | Standard Deviation 6.91 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | -11.90 Millimeters of mercury | Standard Deviation 9.74 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -8.65 Millimeters of mercury | Standard Deviation 7.04 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -7.05 Millimeters of mercury | Standard Deviation 6.89 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | -3.30 Millimeters of mercury | Standard Deviation 5.3 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -6.95 Millimeters of mercury | Standard Deviation 5.44 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -10.00 Millimeters of mercury | Standard Deviation 8.36 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | -6.05 Millimeters of mercury | Standard Deviation 4.83 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -7.55 Millimeters of mercury | Standard Deviation 8.26 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -4.90 Millimeters of mercury | Standard Deviation 5.78 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -6.85 Millimeters of mercury | Standard Deviation 9.32 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -6.10 Millimeters of mercury | Standard Deviation 7.05 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -8.20 Millimeters of mercury | Standard Deviation 6.86 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | -6.05 Millimeters of mercury | Standard Deviation 10.2 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -6.65 Millimeters of mercury | Standard Deviation 7.12 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -5.15 Millimeters of mercury | Standard Deviation 9.48 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | -6.75 Millimeters of mercury | Standard Deviation 10.22 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -6.90 Millimeters of mercury | Standard Deviation 9.73 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -9.15 Millimeters of mercury | Standard Deviation 7.63 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -5.85 Millimeters of mercury | Standard Deviation 8.87 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -7.20 Millimeters of mercury | Standard Deviation 7.52 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -8.50 Millimeters of mercury | Standard Deviation 9.06 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | -5.35 Millimeters of mercury | Standard Deviation 8.93 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -8.60 Millimeters of mercury | Standard Deviation 8.03 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -7.15 Millimeters of mercury | Standard Deviation 7.34 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -10.20 Millimeters of mercury | Standard Deviation 7.37 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -4.70 Millimeters of mercury | Standard Deviation 7 |
| Part A: Cohort 1: Placebo | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -7.80 Millimeters of mercury | Standard Deviation 9.26 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -4.25 Millimeters of mercury | Standard Deviation 6.19 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -6.00 Millimeters of mercury | Standard Deviation 9.87 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -1.67 Millimeters of mercury | Standard Deviation 4.83 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | -1.00 Millimeters of mercury | Standard Deviation 6.78 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -6.25 Millimeters of mercury | Standard Deviation 5.37 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -0.58 Millimeters of mercury | Standard Deviation 10.28 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -6.92 Millimeters of mercury | Standard Deviation 6.5 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | 1.30 Millimeters of mercury | Standard Deviation 7.13 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -9.75 Millimeters of mercury | Standard Deviation 6.57 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -5.00 Millimeters of mercury | Standard Deviation 9.42 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -5.25 Millimeters of mercury | Standard Deviation 13.97 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -6.80 Millimeters of mercury | Standard Deviation 8.25 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -4.17 Millimeters of mercury | Standard Deviation 4.67 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -5.33 Millimeters of mercury | Standard Deviation 8.52 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -8.50 Millimeters of mercury | Standard Deviation 8.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | 1.50 Millimeters of mercury | Standard Deviation 4.71 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -1.25 Millimeters of mercury | Standard Deviation 8.6 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -7.00 Millimeters of mercury | Standard Deviation 5.85 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -5.42 Millimeters of mercury | Standard Deviation 7.64 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -1.67 Millimeters of mercury | Standard Deviation 5.67 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -5.67 Millimeters of mercury | Standard Deviation 7.15 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | 0.08 Millimeters of mercury | Standard Deviation 6.64 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -5.33 Millimeters of mercury | Standard Deviation 10.3 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -3.75 Millimeters of mercury | Standard Deviation 4.12 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -2.67 Millimeters of mercury | Standard Deviation 8.65 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -3.92 Millimeters of mercury | Standard Deviation 7.56 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | 1.50 Millimeters of mercury | Standard Deviation 9.84 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -1.83 Millimeters of mercury | Standard Deviation 6.59 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -2.17 Millimeters of mercury | Standard Deviation 5.27 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -5.58 Millimeters of mercury | Standard Deviation 10.74 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -1.42 Millimeters of mercury | Standard Deviation 10.7 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -1.08 Millimeters of mercury | Standard Deviation 8.67 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | 0.67 Millimeters of mercury | Standard Deviation 11.89 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -4.42 Millimeters of mercury | Standard Deviation 11.63 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -1.75 Millimeters of mercury | Standard Deviation 9.42 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | -5.83 Millimeters of mercury | Standard Deviation 9.23 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -3.83 Millimeters of mercury | Standard Deviation 14.31 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -5.50 Millimeters of mercury | Standard Deviation 9.49 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -3.08 Millimeters of mercury | Standard Deviation 4.19 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | -3.00 Millimeters of mercury | Standard Deviation 7.22 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -4.58 Millimeters of mercury | Standard Deviation 7.37 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -1.42 Millimeters of mercury | Standard Deviation 4.44 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -2.50 Millimeters of mercury | Standard Deviation 5.13 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.17 Millimeters of mercury | Standard Deviation 5.69 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -3.58 Millimeters of mercury | Standard Deviation 4.87 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.75 Millimeters of mercury | Standard Deviation 5.1 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -7.83 Millimeters of mercury | Standard Deviation 5.85 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -0.08 Millimeters of mercury | Standard Deviation 10.03 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -3.67 Millimeters of mercury | Standard Deviation 7.74 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -1.42 Millimeters of mercury | Standard Deviation 6.92 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | 2.00 Millimeters of mercury | Standard Deviation 7.47 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -2.33 Millimeters of mercury | Standard Deviation 6.01 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -5.75 Millimeters of mercury | Standard Deviation 7.37 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -1.42 Millimeters of mercury | Standard Deviation 6.42 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | 0.83 Millimeters of mercury | Standard Deviation 8.88 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -1.08 Millimeters of mercury | Standard Deviation 5.39 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -5.42 Millimeters of mercury | Standard Deviation 4.25 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -6.67 Millimeters of mercury | Standard Deviation 7.93 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -7.67 Millimeters of mercury | Standard Deviation 14.5 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | -5.83 Millimeters of mercury | Standard Deviation 5.19 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -1.67 Millimeters of mercury | Standard Deviation 6.25 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -1.58 Millimeters of mercury | Standard Deviation 6.96 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -0.25 Millimeters of mercury | Standard Deviation 3.76 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.50 Millimeters of mercury | Standard Deviation 7.13 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | 8.08 Millimeters of mercury | Standard Deviation 8.11 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | -1.67 Millimeters of mercury | Standard Deviation 5.6 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | -2.75 Millimeters of mercury | Standard Deviation 4.91 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -1.33 Millimeters of mercury | Standard Deviation 4.54 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -4.17 Millimeters of mercury | Standard Deviation 3.92 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -3.25 Millimeters of mercury | Standard Deviation 6.02 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -6.75 Millimeters of mercury | Standard Deviation 7.76 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -5.92 Millimeters of mercury | Standard Deviation 4.62 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -6.25 Millimeters of mercury | Standard Deviation 7.01 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | 1.17 Millimeters of mercury | Standard Deviation 10.69 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | -3.50 Millimeters of mercury | Standard Deviation 6.19 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -6.67 Millimeters of mercury | Standard Deviation 17.26 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -3.58 Millimeters of mercury | Standard Deviation 5.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | -3.67 Millimeters of mercury | Standard Deviation 8.22 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | -5.67 Millimeters of mercury | Standard Deviation 6.47 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -5.42 Millimeters of mercury | Standard Deviation 7.81 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -5.17 Millimeters of mercury | Standard Deviation 5.83 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -1.83 Millimeters of mercury | Standard Deviation 15.28 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -7.83 Millimeters of mercury | Standard Deviation 14.75 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -2.08 Millimeters of mercury | Standard Deviation 5.56 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | -11.08 Millimeters of mercury | Standard Deviation 15.23 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -8.83 Millimeters of mercury | Standard Deviation 7.45 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -9.83 Millimeters of mercury | Standard Deviation 18.11 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -13.00 Millimeters of mercury | Standard Deviation 13.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -9.33 Millimeters of mercury | Standard Deviation 18.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -2.92 Millimeters of mercury | Standard Deviation 8.23 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | -0.08 Millimeters of mercury | Standard Deviation 15.46 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | -5.92 Millimeters of mercury | Standard Deviation 14.17 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -6.92 Millimeters of mercury | Standard Deviation 10.58 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -8.00 Millimeters of mercury | Standard Deviation 9.17 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -7.67 Millimeters of mercury | Standard Deviation 15.08 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -6.50 Millimeters of mercury | Standard Deviation 13.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -8.25 Millimeters of mercury | Standard Deviation 7.9 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | 0.08 Millimeters of mercury | Standard Deviation 11 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -6.83 Millimeters of mercury | Standard Deviation 6.12 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | -5.25 Millimeters of mercury | Standard Deviation 6.26 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -7.25 Millimeters of mercury | Standard Deviation 16.23 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -4.50 Millimeters of mercury | Standard Deviation 10.31 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -3.00 Millimeters of mercury | Standard Deviation 5.93 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -2.33 Millimeters of mercury | Standard Deviation 13.01 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.75 Millimeters of mercury | Standard Deviation 8.62 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -4.00 Millimeters of mercury | Standard Deviation 18.1 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -7.25 Millimeters of mercury | Standard Deviation 5.82 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -2.75 Millimeters of mercury | Standard Deviation 8.93 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -3.50 Millimeters of mercury | Standard Deviation 10.48 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -4.08 Millimeters of mercury | Standard Deviation 12.69 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -3.00 Millimeters of mercury | Standard Deviation 7.54 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -5.92 Millimeters of mercury | Standard Deviation 15.81 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -2.33 Millimeters of mercury | Standard Deviation 11.79 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -8.00 Millimeters of mercury | Standard Deviation 9.98 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -6.75 Millimeters of mercury | Standard Deviation 7.13 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | -8.33 Millimeters of mercury | Standard Deviation 11.99 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.08 Millimeters of mercury | Standard Deviation 12.64 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -9.50 Millimeters of mercury | Standard Deviation 13.57 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -8.42 Millimeters of mercury | Standard Deviation 10.95 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | 1.00 Millimeters of mercury | Standard Deviation 5.06 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -9.33 Millimeters of mercury | Standard Deviation 13.52 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | 2.00 Millimeters of mercury | Standard Deviation 8.4 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -8.08 Millimeters of mercury | Standard Deviation 16.69 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | 0.83 Millimeters of mercury | Standard Deviation 10.93 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 5.00 Millimeters of mercury | Standard Deviation 5.68 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | 4.58 Millimeters of mercury | Standard Deviation 3.99 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -0.25 Millimeters of mercury | Standard Deviation 13.15 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | 2.67 Millimeters of mercury | Standard Deviation 3.66 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | 2.67 Millimeters of mercury | Standard Deviation 13.53 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -1.08 Millimeters of mercury | Standard Deviation 5.7 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -5.00 Millimeters of mercury | Standard Deviation 7.06 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -2.00 Millimeters of mercury | Standard Deviation 3.79 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | -3.17 Millimeters of mercury | Standard Deviation 7.47 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -5.08 Millimeters of mercury | Standard Deviation 4.73 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -1.25 Millimeters of mercury | Standard Deviation 4.47 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | -5.00 Millimeters of mercury | Standard Deviation 6.54 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -3.33 Millimeters of mercury | Standard Deviation 2.82 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | -2.42 Millimeters of mercury | Standard Deviation 8.75 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -3.58 Millimeters of mercury | Standard Deviation 6.44 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | -9.08 Millimeters of mercury | Standard Deviation 11.13 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -2.75 Millimeters of mercury | Standard Deviation 7.06 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -3.92 Millimeters of mercury | Standard Deviation 14.39 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -6.83 Millimeters of mercury | Standard Deviation 11.57 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -4.08 Millimeters of mercury | Standard Deviation 16.53 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 2; n=10,6,6,6,6,6 | -2.25 Millimeters of mercury | Standard Deviation 8.85 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 11; n=10,6,6,6,6,6 | -3.92 Millimeters of mercury | Standard Deviation 7.21 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 5; n=10,6,6,6,6,6 | -11.17 Millimeters of mercury | Standard Deviation 8.52 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 3; n=10,6,6,6,6,6 | -5.58 Millimeters of mercury | Standard Deviation 5.24 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -3.67 Millimeters of mercury | Standard Deviation 10.24 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 | -7.50 Millimeters of mercury | Standard Deviation 14.55 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 3; n=10,6,6,6,6,6 | -2.17 Millimeters of mercury | Standard Deviation 7.16 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 15; n=10,5,6,6,6,6 | -4.08 Millimeters of mercury | Standard Deviation 7.28 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 10; n=10,6,6,6,6,6 | -6.50 Millimeters of mercury | Standard Deviation 12.08 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 12; n=10,6,6,6,6,6 | -4.25 Millimeters of mercury | Standard Deviation 12.5 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 11; n=10,6,6,6,6,6 | -9.50 Millimeters of mercury | Standard Deviation 10.31 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 8; n=10,6,6,6,6,6 | -4.75 Millimeters of mercury | Standard Deviation 10.01 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 4; n=10,6,6,6,6,6 | -3.67 Millimeters of mercury | Standard Deviation 6.68 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 6; n=10,6,6,6,6,6 | -6.67 Millimeters of mercury | Standard Deviation 7.94 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -1.17 Millimeters of mercury | Standard Deviation 10.63 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | -5.67 Millimeters of mercury | Standard Deviation 8.64 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 10; n=10,6,6,6,6,6 | -15.67 Millimeters of mercury | Standard Deviation 18.97 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | -3.92 Millimeters of mercury | Standard Deviation 13.91 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 9; n=10,6,6,6,6,6 | -4.42 Millimeters of mercury | Standard Deviation 6.73 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 4; n=10,6,6,6,6,6 | -9.42 Millimeters of mercury | Standard Deviation 6.26 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 | 0.33 Millimeters of mercury | Standard Deviation 8.68 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 6; n=10,6,6,6,6,6 | -10.33 Millimeters of mercury | Standard Deviation 15.03 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 15; n=10,5,6,6,6,6 | -5.42 Millimeters of mercury | Standard Deviation 8.46 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 13; n=10,6,6,6,6,6 | -2.67 Millimeters of mercury | Standard Deviation 8.17 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 5; n=10,6,6,6,6,6 | -3.33 Millimeters of mercury | Standard Deviation 9.36 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Follow-up (Day 25); n=10,6,6,6,6,6 | -2.83 Millimeters of mercury | Standard Deviation 7.81 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -0.83 Millimeters of mercury | Standard Deviation 7.77 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 12; n=10,6,6,6,6,6 | -0.50 Millimeters of mercury | Standard Deviation 7.62 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 | -9.50 Millimeters of mercury | Standard Deviation 6.98 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -8.08 Millimeters of mercury | Standard Deviation 7.39 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 | -3.33 Millimeters of mercury | Standard Deviation 6.77 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 9; n=10,6,6,6,6,6 | -9.00 Millimeters of mercury | Standard Deviation 13.7 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 | 0.33 Millimeters of mercury | Standard Deviation 8.85 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | DBP; Day 8; n=10,6,6,6,6,6 | -4.42 Millimeters of mercury | Standard Deviation 7.49 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 13; n=10,6,6,6,6,6 | -6.58 Millimeters of mercury | Standard Deviation 9.84 |
| Part B: GSK3352589 200 mg BID | Part B: Change From Baseline in SBP and DBP | SBP; Day 2; n=10,6,6,6,6,6 | -9.42 Millimeters of mercury | Standard Deviation 11.58 |
Primary
Part B: Cmax Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.1655 Nanogram per milliliter | Geometric Coefficient of Variation 74.3 |
| Part A: Cohort 1: Placebo | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.1308 Nanogram per milliliter | Geometric Coefficient of Variation 93 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.1394 Nanogram per milliliter | Geometric Coefficient of Variation 51.2 |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.1919 Nanogram per milliliter | Geometric Coefficient of Variation 31.3 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.5255 Nanogram per milliliter | Geometric Coefficient of Variation 17.9 |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.7149 Nanogram per milliliter | Geometric Coefficient of Variation 26.4 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.8191 Nanogram per milliliter | Geometric Coefficient of Variation 78.5 |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.260 Nanogram per milliliter | Geometric Coefficient of Variation 36.7 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.526 Nanogram per milliliter | Geometric Coefficient of Variation 43.6 |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Cmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.6607 Nanogram per milliliter | Geometric Coefficient of Variation 67.4 |
Primary
Part B: Number of Participants With Abnormal ECG Findings
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 1 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal NCS | 1 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 1; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Follow-up (Day 25); Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 7; Pre-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 7; 4 Hours Post-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 14; 4 Hours Post-dose; Abnormal NCS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Baseline (Day 1; Pre-dose); Abnormal CS | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal ECG Findings | Day 14; Pre-dose; Abnormal NCS | 0 Participants |
Primary
Part B: Number of Participants With Abnormal Findings After Physical Examination
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time frame: Up to 25 days
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings After Physical Examination | 0 Participants |
Primary
Part B: Number of Participants With Abnormal Findings for Urine Parameters
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 1 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 1 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 2 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 3 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 1 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 1 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 1 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Occult blood; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Nitrite; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 15 | 2 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 15 | 1 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Leukocyte esterase; Baseline (Day -2) | 1 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Ketones; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Bilirubin; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Glucose; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 15 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Day 7 | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Protein; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Urobilinogen; Follow-up (Day 25) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | Specific gravity; Baseline (Day -2) | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With Abnormal Findings for Urine Parameters | pH; Day 15 | 0 Participants |
Primary
Part B: Number of Participants With SAEs and Non-SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time frame: Up to 25 days
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part A: Cohort 1: Placebo | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 9 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 5 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 6 Participants |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 2 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 5 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With SAEs and Non-SAEs | Any SAE | 0 Participants |
| Part B: GSK3352589 200 mg BID | Part B: Number of Participants With SAEs and Non-SAEs | Any non-SAE | 5 Participants |
Primary
Part B: Tmax Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Population: Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Cohort 1: Placebo | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.767 Hours |
| Part A: Cohort 1: Placebo | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.500 Hours |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 1.00 Hours |
| Part A: Cohort 1: GSK3352589 2 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.500 Hours |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 1.00 Hours |
| Part A: Cohort 1: GSK3352589 5 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.50 Hours |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 1.75 Hours |
| Part A: Cohort 1: GSK3352589 15 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 1.50 Hours |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 1; n=6, 6, 6, 6, 6 | 0.750 Hours |
| Part A: Cohort 1: GSK3352589 50 mg | Part B: Tmax Following Repeat Dose Administration of GSK3352589 | Day 14; n=5, 6, 6, 6, 6 | 0.500 Hours |