A Phase 1, First Time in Human (FTIH) Study to Evaluate G... | NCT03154086 | Trialant
NCT03154086
Sponsor
GlaxoSmithKline
Status
Completed
Last Update Posted
Aug 9, 2019Actual
Enrollment
68Actual
Phase
Phase 1
Conditions
Irritable Bowel Syndrome
Interventions
GSK3352589
Matching Placebo
Countries
Australia
Protocol Section
Identification Module
NCT ID
NCT03154086
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
207440
Secondary IDs
Not provided
Brief Title
A Phase 1, First Time in Human (FTIH) Study to Evaluate GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Volunteers
Official Title
A Phase I, First Time in Human, Two Part, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Single and Repeat Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
Jun 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 17, 2017Actual
Primary Completion Date
Mar 5, 2018Actual
Completion Date
Mar 5, 2018Actual
First Submitted Date
May 12, 2017
First Submission Date that Met QC Criteria
May 12, 2017
First Posted Date
May 15, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Mar 5, 2019
Results First Submitted that Met QC Criteria
Jun 28, 2019
Results First Posted Date
Aug 9, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 28, 2019
Last Update Posted Date
Aug 9, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
GlaxoSmithKlineINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Irritable Bowel Syndrome
Keywords
REarranged during Transfection
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
68Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
GSK3352589
Drug
It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg
Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Up to 64 days in Cohort 1
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.
Up to 30 days in Cohort 2
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.
Up to 30 days in Cohort 3
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.
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Reedy BA, O'Connor-Semmes R, Hacquoil K, Gorycki P, Verticelli A, Molga A. First-in-Human Study for a Selective Rearranged During Transfection Tyrosine Kinase Inhibitor, GSK3352589, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Apr;10(4):334-345. doi: 10.1002/cpdd.911. Epub 2021 Feb 19.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
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.
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Periods
Title
Milestones
Reasons Not Completed
Part A: Cohort1 Period1 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 31, 2017
Nov 21, 2018
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed
Experimental
Subjects will receive single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Part A: Cohort 2: Placebo Fasted/Placebo Fed
Experimental
Subjects will receive single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: Matching Placebo
Part A:Cohort 3: GSK3352589 150 mg/Placebo
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 3: Placebo/GSK3352589 400 mg
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Drug: Matching Placebo
Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg
Experimental
Subjects will receive 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. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Drug: GSK3352589
Part B: GSK3352589
Experimental
Subjects will receive repeat oral doses of GSK3352589 of 5 mg, 15 mg, 50 mg, 100 mg or 200 mg twice daily administered for 14 days.
Drug: GSK3352589
Part B: Placebo
Placebo Comparator
Subjects will receive repeat oral doses of placebo twice a day tablet administered for 14 days.
Drug: Matching Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg
Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg
Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed
Part A:Cohort 3: GSK3352589 150 mg/Placebo
Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg
Part A:Cohort 3: Placebo/GSK3352589 400 mg
Part B: GSK3352589
Matching Placebo
Drug
It will be available across all strengths to match active drug in the form of tablet for oral administration.
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg
Part A: Cohort 2: Placebo Fasted/Placebo Fed
Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg
Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg
Part A:Cohort 3: GSK3352589 150 mg/Placebo
Part A:Cohort 3: Placebo/GSK3352589 400 mg
Part B: Placebo
Up to 25 days
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.
Up to 64 days in Cohort 1
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.
Up to 30 days in Cohort 2
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.
Up to 30 days in Cohort 3
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.
Up to 25 days
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
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.
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)
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
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)
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
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)
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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.
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)
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).
Up to 64 days in Cohort 1
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).
Up to 30 days in Cohort 2
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).
Up to 30 days in Cohort 3
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).
Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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).
Baseline (Day-1) and Day 3
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).
Baseline (Day -1) and Day 3
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.
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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.
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
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.
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
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.
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
FG001
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.
FG002
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.
FG003
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.
FG004
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.
FG005
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.
FG006
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.
FG007
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.
FG008
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.
FG009
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.
FG010
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.
FG011
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.
FG012
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.
FG013
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.
FG014
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.
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
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COMPLETED
FG0002 subjects
FG0012 subjects
FG0022 subjects
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FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
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NOT COMPLETED
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FG0090 subjects
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Part A: Cohort1 Washout1 (Up to 14 Days)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
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FG0070 subjects
FG0080 subjects
FG0090 subjects
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COMPLETED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0031 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort1 Period2 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjectsOne replacement participant (par) was enrolled and dosed
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FG0090 subjects
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COMPLETED
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FG0032 subjects
FG004
NOT COMPLETED
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FG004
PartA: Cohort1 Washout2 (Up to 14 Days)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
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FG0050 subjects
FG0060 subjects
FG0070 subjects
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FG0090 subjects
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FG0140 subjects
COMPLETED
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0032 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG003
Part A: Cohort1 Period3 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjectsOne replacement par was enrolled and dosed
FG0022 subjects
FG0032 subjects
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FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Cohort1 Washout3 (Up to 14 Days)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0032 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
Part A: Cohort1 Period4 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0003 subjects1 par was not dosed on day of dosing due to elevated lab; hence 1 replacement was enrolled and dosed
FG0012 subjects
FG0021 subjects
FG0032 subjects
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FG0050 subjects
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FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
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FG0140 subjects
COMPLETED
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0032 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort2 Period1 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
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FG0046 subjects
FG0052 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
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COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
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FG0030 subjects
FG004
Part A: Cohort2 Washout1 (Up to 14 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0046 subjects
FG0052 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
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FG0130 subjects
FG0140 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Cohort2 Period2 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0046 subjects
FG0052 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Cohort3 Period1 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0062 subjects
FG0072 subjects
FG0084 subjects
FG0090 subjects
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FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Cohort3 Washout1 (Up to 14 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0062 subjects
FG0072 subjects
FG0084 subjects
FG0090 subjects
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FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Cohort3 Period2 (Up to 3 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0062 subjects
FG0072 subjects
FG0085 subjects1 par was unwell on Day-1 of Period 2 and discontinued; hence,1 replacement was enrolled and dosed
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part B (Up to 25 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
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FG0080 subjects
FG00910 subjects
FG0106 subjects
FG0116 subjects
FG0126 subjects
FG0136 subjects
FG0146 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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.
BG001
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.
BG002
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.
BG003
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.
BG004
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.
BG005
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.
BG006
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.
BG007
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.
BG008
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.
BG009
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.
BG010
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.
BG011
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.
BG012
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.
BG013
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.
BG014
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.
BG015
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0013
BG0022
BG0033
BG0046
BG0052
BG0062
BG0072
BG0085
BG00910
BG0106
BG0116
BG0126
BG0136
BG0146
BG01568
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00043.0± 14.00
BG00126.7± 4.73
BG00233.5± 9.19
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Native-Asian
Title
Measurements
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
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.
Posted
Count of Participants
Participants
Up to 64 days in Cohort 1
ID
Title
Description
OG000
Part A: Cohort 1: Placebo
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG003
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
OG004
Part A: Cohort 1: GSK3352589 50 mg
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Units
Counts
Participants
OG0008
OG0016
OG0026
OG003
Title
Denominators
Categories
Any SAE
Title
Measurements
OG0000
OG0011
OG0020
OG003
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.
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 2
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 3
ID
Title
Description
OG000
Part A: Cohort 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
OG001
Part A: Cohort 3: GSK3352589 150 mg
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
OG002
Part A: Cohort 3: GSK3352589 400 mg
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
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.
Safety population
Posted
Count of Participants
Participants
Up to 25 days
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
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.
Safety population
Posted
Count of Participants
Participants
Up to 64 days in Cohort 1
ID
Title
Description
OG000
Part A: Cohort 1: Placebo
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG003
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.
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 2
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 3
ID
Title
Description
OG000
Part A: Cohort 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
OG001
Part A: Cohort 3: GSK3352589 150 mg
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
OG002
Part A: Cohort 3: GSK3352589 400 mg
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
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.
Safety population
Posted
Count of Participants
Participants
Up to 25 days
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Posted
Count of Participants
Participants
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
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.
Safety population
Posted
Count of Participants
Participants
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
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.
Safety population
Posted
Count of Participants
Participants
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)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
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.
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.
Posted
Mean
Standard Deviation
Millimeters of mercury
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Millimeters of mercury
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Posted
Mean
Standard Deviation
Millimeters of mercury
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)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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.
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.
Posted
Mean
Standard Deviation
Beats per minute
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Beats per minute
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Posted
Mean
Standard Deviation
Beats per minute
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)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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.
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.
Posted
Mean
Standard Deviation
Celsius
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Celsius
Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Posted
Mean
Standard Deviation
Celsius
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)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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).
Safety population
Posted
Count of Participants
Participants
Up to 64 days in Cohort 1
ID
Title
Description
OG000
Part A: Cohort 1: Placebo
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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).
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 2
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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).
Safety population
Posted
Count of Participants
Participants
Up to 30 days in Cohort 3
ID
Title
Description
OG000
Part A: Cohort 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
OG001
Part A: Cohort 3: GSK3352589 150 mg
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
OG002
Part A: Cohort 3: GSK3352589 400 mg
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
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).
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Posted
Mean
Standard Deviation
Units on a scale
Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
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.
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.
Posted
Mean
Standard Deviation
10^9 cells per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
10^9 cells per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Posted
Mean
Standard Deviation
10^9 cells per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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.
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.
Posted
Mean
Standard Deviation
10^12 cells per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
10^12 cells per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
10^12 cells per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
Part A: Cohort 2: GSK3352589 Fed 25 mg
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Posted
Mean
Standard Deviation
Femtoliter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
Femtoliter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Femtoliter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Posted
Mean
Standard Deviation
Picogram
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
Picogram
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Picogram
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Posted
Mean
Standard Deviation
Proportion of red blood cells in blood
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
Proportion of red blood cells in blood
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Proportion of red blood cells in blood
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
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.
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.
Posted
Mean
Standard Deviation
Units per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Units per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Units per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
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.
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.
Posted
Mean
Standard Deviation
Micromoles per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Micromoles per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Micromoles per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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.
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.
Posted
Mean
Standard Deviation
Millimoles per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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.
Safety population
Posted
Mean
Standard Deviation
Millimoles per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Millimoles per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
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.
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.
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG003
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.
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Mean
Standard Deviation
Grams per liter
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
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).
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.
Posted
Count of Participants
Participants
Baseline (Day-1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 1 and 3: Placebo
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 5 mg
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).
Safety population
Posted
Count of Participants
Participants
Baseline (Day -1) and Day 3
ID
Title
Description
OG000
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
OG001
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
OG002
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
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.
Safety population
Posted
Count of Participants
Participants
Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
ID
Title
Description
OG000
Part B: Placebo BID
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG003
Part B: GSK3352589 50 mg BID
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.
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.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG002
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
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.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
OG003
Part A: Cohort 1: GSK3352589 50 mg
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.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
OG003
Part A: Cohort 1: GSK3352589 50 mg
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
OG002
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
OG003
Part A: Cohort 1: GSK3352589 50 mg
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.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 2: GSK3352589 Fed 25 mg
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Units
Counts
Participants
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.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 2: GSK3352589 Fed 25 mg
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Units
Counts
Participants
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.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
OG001
Part A: Cohort 2: GSK3352589 Fed 25 mg
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Units
Counts
Participants
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*Nanogram per milliliter
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
ID
Title
Description
OG000
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 50 mg BID
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*Nanogram per milliliter
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
ID
Title
Description
OG000
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 50 mg BID
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*Nanogram per milliliter
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
ID
Title
Description
OG000
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 50 mg BID
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanogram per milliliter
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
ID
Title
Description
OG000
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 50 mg BID
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
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.
Pharmacokinetic Parameter Population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Posted
Median
Full Range
Hours
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
ID
Title
Description
OG000
Part B: GSK3352589 5 mg BID
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
OG001
Part B: GSK3352589 15 mg BID
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
OG002
Part B: GSK3352589 50 mg BID
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Time Frame
Serious adverse events (SAEs) and non-SAEs were collected up to 64 days in Cohort 1, up to 30 days in Cohort 2, up to 30 days in Cohort 3 each in Part A of the study and up to 25 days in Part B of the study.
Description
SAEs and non-SAEs were collected using Safety Population.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: Cohort 1: Placebo
Participants received placebo tablet matching GSK3352589 orally in each Period of Cohort 1 in Part A of the study.
0
8
0
8
3
8
EG001
Part A: Cohort 1: GSK3352589 2 mg
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
0
6
1
6
5
6
EG002
Part A: Cohort 1: GSK3352589 5 mg
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
0
6
0
6
3
6
EG003
Part A: Cohort 1: GSK3352589 15 mg
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
0
6
0
6
2
6
EG004
Part A: Cohort 1: GSK3352589 50 mg
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
0
5
0
5
2
5
EG005
Part A: Cohort 2: Fasted Placebo
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
0
2
0
2
1
2
EG006
Part A: Cohort 2: Fed Placebo
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
0
2
0
2
0
2
EG007
Part A: Cohort 2: GSK3352589 Fed 25 mg
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
0
6
0
6
3
6
EG008
Part A: Cohort 2: GSK3352589 Fasted 25 mg
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
0
6
0
6
1
6
EG009
Part A: Cohort 3: Placebo
Participants received placebo tablet matching GSK3352589 in each Period of Cohort 3 in Part A of the study.
0
4
0
4
2
4
EG010
Part A: Cohort 3: GSK3352589 150 mg
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
0
6
0
6
3
6
EG011
Part A: Cohort 3: GSK3352589 400 mg
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
0
5
0
5
1
5
EG012
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.
0
10
0
10
9
10
EG013
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.
0
6
0
6
5
6
EG014
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.
0
6
0
6
6
6
EG015
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.
0
6
0
6
2
6
EG016
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.
0
6
0
6
5
6
EG017
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.
0
6
0
6
5
6
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain lower
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected5 at risk
EG0050 events0 affected2 at risk
EG0060 events0 affected2 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected6 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
EG0110 events0 affected5 at risk
EG0120 events0 affected10 at risk
EG0130 events0 affected6 at risk
EG0140 events0 affected6 at risk
EG0150 events0 affected6 at risk
EG0160 events0 affected6 at risk
EG0170 events0 affected6 at risk
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Headache
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected5 at risk
EG0050 events0 affected2 at risk
EG0060 events0 affected2 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected6 at risk
EG0091 events1 affected4 at risk
EG0102 events2 affected6 at risk
EG0110 events0 affected5 at risk
EG0126 events4 affected10 at risk
EG0132 events2 affected6 at risk
EG0142 events1 affected6 at risk
EG0150 events0 affected6 at risk
EG0163 events2 affected6 at risk
EG0170 events0 affected6 at risk
Head discomfort
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Syncope
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tension headache
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dry throat
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nasal obstruction
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site bruise
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site pain
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chest discomfort
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hunger
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Malaise
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vessel puncture site bruise
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Faeces hard
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0001 events1 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Liver function test abnormal
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Food allergy
Immune system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Flushing
Vascular disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastrointestinal sounds abnormal
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site related reaction
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Asthenia
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site mass
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Influenza like illness
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Weight decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Joint stiffness
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oropharyngeal discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 20.1
Systematic Assessment
EG0000 events0 affected8 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.