Safety, Tolerability and Pharmacokinetics (PKs) Investiga... | NCT03874234 | Trialant
NCT03874234
Sponsor
GlaxoSmithKline
Status
Terminated
Last Update Posted
Feb 27, 2023Actual
Enrollment
25Actual
Phase
Phase 1
Conditions
Leishmaniasis
Interventions
GSK3186899
Placebo
Countries
United Kingdom
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT03874234
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
208436
Secondary IDs
Not provided
Brief Title
Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects
Official Title
A Randomized, Double-blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) and Repeat Doses of GSK3186899 in Healthy Participants
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
May 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The trial was terminated early following strategic review after emergence of nonclinical data with a non-GlaxoSmithKline asset.
Expanded Access Info
No
Start Date
Apr 30, 2019Actual
Primary Completion Date
Oct 17, 2019Actual
Completion Date
Oct 17, 2019Actual
First Submitted Date
Mar 12, 2019
First Submission Date that Met QC Criteria
Mar 12, 2019
First Posted Date
Mar 14, 2019Actual
Results Waived
Not provided
Results First Submitted Date
May 24, 2022
Results First Submitted that Met QC Criteria
May 24, 2022
Results First Posted Date
Feb 27, 2023Actual
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
May 24, 2022
Last Update Posted Date
Feb 27, 2023Actual
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
The purpose of this study is to evaluate the safety, tolerability and PK profile of single and repeat ascending doses of GSK3186899 in healthy subjects. This is a Phase 1 first time in human study, to investigate the effect of food on PK of GSK3186899. This study will consists of two parts. Part A (dose escalation phase) will be a single ascending, sequential cross-over design in cohorts 1, 2 and 3 of subjects. Cohort 1 and 2 will be 4-way cross-over which includes 4 dosing regimens of GSK3186899 and placebo (3:1 ratio) under fasted conditions. Cohort 3 will be 2-way cross-over which includes 2 treatment periods, 2 dosing regimens in fasted and fed conditions. In Part B (repeat dose escalation phase) subjects will be randomized to receive repeat doses of either GSK3186899 or placebo (3:1 ratio) in either fed or fasted conditions. Part B will be conducted based on the review of all safety, tolerability and PK data from Part A. The study duration includes screening, treatment periods and follow-up.
Detailed Description
Not provided
Conditions Module
Conditions
Leishmaniasis
Keywords
Dose escalation phase
First time in human
Single ascending dose
Multiple ascending dose
GSK3186899
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
25Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: Subjects receiving GSK3186899 + placebo in Cohort 1
Experimental
Subjects will receive 3 single ascending oral doses (SAD) of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 1 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.
Drug: GSK3186899
Drug: Placebo
Part A: Subjects receiving GSK3186899 + placebo in Cohort 2
Experimental
Subjects will receive 3 SAD of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 2 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.
Drug: GSK3186899
Drug: Placebo
Part A: Subjects receiving GSK3186899 in Cohort 3
Experimental
Subjects will receive GSK3186899 orally, under fasted condition and fed conditions on Day 1 of cohort 3 in each of the two treatment periods. There will be a wash out period of at least 10 days between each treatment period. A dose level will be determined based on the effect of food on the safety, tolerability and PK of a single dose of GSK3186899, with dose level selected from Cohorts 1 and 2.
Drug: GSK3186899
Part B: Subjects receiving GSK3186899
Experimental
Subjects will receive GSK3186899, orally, twice daily (BID) on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
GSK3186899
Drug
GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Up to Week 12
Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Up to Week 9
Part B: Number of Participants With Non-SAEs and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Secondary Outcomes
Measure
Description
Time Frame
Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3186899. PK Population consisted of all participants in the Safety Population who received at least 1 non-missing PK assessment.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria
Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m^2) (inclusive).
Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP).
Capable of giving signed informed consent.
Exclusion Criteria
History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Previous history of leishmaniasis.
ALT >1.5* upper limit of normal (ULN).
Bilirubin >1.5*ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Current or past history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).
Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton-pump inhibitors (PPIs) or anti-H2 antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the Investigator in consultation with the medical monitor.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates participation in the study.
Regular use of known drugs of abuse.
Subjects with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate glomerular filtration rate (GFR) <=80 (mL/minute/1.73m^2).
Presence of Hepatitis B surface antigen (HBsAg) or Positive Hepatitis C antibody test result at screening.
Positive human immunodeficiency virus (HIV) antibody test.
Positive pre-study drug/alcohol screen.
Presence of clinically significant hematuria and/or proteinuria.
Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening.
Part A (Food effect) Cohort 3 only: Subject must have no dietary restrictions (example, lactose intolerance) or inability to eat an adapted standard meal (includes 35-40 percent fat content).
Part A (Food effect) Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (example, cholelithiasis) within 14 days prior to receiving the study treatment.
Part B only: Early morning cortisol <420 nanomoles per liter (nmol/L) and inadequate response (rise of <250 millimoles per liter (mmol/L) from Baseline) to adrenocorticotropic hormone (ACTH) stimulation test at Day -1.
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
55 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
GSK Clinical Trials
GlaxoSmithKline
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
GSK Investigational Site
Cambridge
CB2 2GG
United Kingdom
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
A total 25 participants were enrolled (Enrolled Population consisted of all participants who passed screening and entered the study) in this study (Part A: Cohort 1- 11 participants, Cohort 2- 14 participants). Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Recruitment Details
This was 2-part study. Part A comprised of 3 Cohorts (Cohorts 1, 2 and 3); Part B comprised 3 cohorts (Cohorts 4, 5 and 6). Study was terminated after completion of Cohort 2, Period 3 of Part A following strategic review after emergence of nonclinical data with non-GlaxoSmithKline asset. Hence, no participants were enrolled in Cohort 2 Period 4 and Cohort 3 of Part A and in all Cohorts of Part B.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: Cohort 1-GSK3186899 30 mg/60 mg/120 mg/Placebo
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 milligram (mg) on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
FG001
Part A:Cohort 1-GSK3186899 30 mg/60 mg/Placebo/300 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
FG002
Part A:Cohort 1-GSK3186899 30 mg/Placebo/120 mg/300 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
FG003
Part A:Cohort 1-Placebo/GSK3186899 60 mg/120 mg/300 mg
Participants in Part A Cohort 1 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
FG004
Part A:Cohort 2-GSK3186899 300 mg/600 mg/800 mg/Placebo
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
FG005
Part A:Cohort 2-GSK3186899 300 mg/600 mg/Placebo/Dose Level 7
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
FG006
Part A:Cohort 2-GSK3186899 300 mg/Placebo/800 mg/Dose Level 7
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
FG007
Part A:Cohort 2-Placebo/GSK3186899 600 mg/800 mg/Dose Level 7
Participants in Part A Cohort 2 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
FG008
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
FG009
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
FG010
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
FG011
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
FG012
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Periods
Title
Milestones
Reasons Not Completed
Part A: Cohort 1-Period 1 (Day1)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
FG004
Safety Population Consisted of All Randomized Participants Who Received at Least 1 Dose of Treatment
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0032 subjects
COMPLETED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0031 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PartA:Cohort1-WashoutPeriod1(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG003
Part A: Cohort 1-Period 2 (Day1)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG003
PartA:Cohort1-WashoutPeriod2(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0001 subjects
FG0012 subjects
FG0022 subjects
FG003
Part A: Cohort 1-Period 3 (Day1)
Type
Comment
Milestone Data
STARTED
FG0002 subjectsNew participant enrolled and dosed.
FG0012 subjects
FG0022 subjects
FG003
PartA:Cohort1-WashoutPeriod3(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG003
Part A: Cohort 1-Period 4 (Day1)
Type
Comment
Milestone Data
STARTED
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG003
Part A: Cohort 2-Period 1 (Day1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PartA:Cohort2-WashoutPeriod1(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort 2-Period 2 (Day1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PartA:Cohort2-WashoutPeriod2(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort 2-Period 3 (Day1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PartA:Cohort2-WashoutPeriod3(Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort 2-Period 4 (Day1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort 3- Period 1 (Day 1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PartA:Cohort3-WashoutPeriod (Upto Day10)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A: Cohort 3- Period 2 (Day 1)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part B: Cohorts 4 to 6 (Days 1 to 10)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
This study was terminated after completion of Cohort 2, Period 3 of Part A following strategic review after emergence of nonclinical data with non-GlaxoSmithKline asset. Hence, no participants were enrolled in Cohort 2 Period 4 and Cohort 3 of Part A and in all Cohorts of Part B. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: Cohort 1-GSK3186899 30 mg/60 mg/120 mg/Placebo
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 milligram (mg) on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Baseline characteristics were reported for Safety Population which consisted of all randomized participants who received at least one dose of study treatment.
Outcome Measures Module
Outcome Measures
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- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
Adverse Events Module
Frequency Threshold
0
Time Frame
All-cause mortality, non-SAE and SAE were collected up to Week 12 in Part A. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as stopping criteria was reached with 800 mg dose and no further dose escalation was recommended.
Description
All-cause mortality,non-SAE,SAE were collected using Safety Population in Cohorts1and2 of PartA.1 participant from Enrolled Population(N=25) did not receive study treatment,hence was not included in Safety Population(N=24).Data was not collected in Cohort2-Period4,Cohort3 of PartA and PartB as study was terminated and no participant was enrolled in these cohorts/parts.
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: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
Subjects will receive escalating doses of GSK3186899 and placebo in Part A of the study. Subjects will receive repeat doses either of GSK3186899 or placebo in Part B of the study.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
This will be a double-blind study. Subjects and Investigator will be blinded to the study treatment.
Who Masked
ParticipantInvestigator
Drug: GSK3186899
Part B: Subjects receiving placebo
Placebo Comparator
Subjects will receive placebo, orally, BID on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.
Drug: Placebo
Part A: Subjects receiving GSK3186899 + placebo in Cohort 1
Part A: Subjects receiving GSK3186899 + placebo in Cohort 2
Part A: Subjects receiving GSK3186899 in Cohort 3
Part B: Subjects receiving GSK3186899
Placebo
Drug
Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.
Part A: Subjects receiving GSK3186899 + placebo in Cohort 1
Part A: Subjects receiving GSK3186899 + placebo in Cohort 2
Part B: Subjects receiving placebo
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
PCI ranges were <0.0 or >0.1*10^9 cells per(/)liter(L)(basophils), <37 or >50 proportion of red blood cells(RBC) in blood(hematocrit),<130 or >170 grams/L(hemoglobin[Hb]), <1.2 or >3.65*10^9cells(c)/L (lymphocytes),<0.2 or >1*10^9c/L(monocytes), <2 or >7.5*10^9c/L(neutrophils), <150 or >400*10^9 c/L(platelets), <3.0 or >10*10^9c/L(white blood cell[WBC]count), <4.4 or >5.8*10^12 c/L(RBC count), <80 or >99 femtoliter(mean corpuscular[MC] volume), <26.0 or >33.5 picogram(MC Hb), <0.0 or >0.4*10^9 c/L(eosinophils). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became within range, were recorded in To within Range or No Change category.Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100 percentage(%).
Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Up to Week 9
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
PCI ranges were <34 or >50 grams/L(albumin),<40 or >129 international units/L[IU/L](alkaline phosphatase),<10 or >50 IU/L(alanine aminotransferase),<0 or >37(aspartate aminotransferase), <0 or >20 micromoles(mcmol)/L (direct bilirubin),<0 or >20 mcmol/L(bilirubin), <2.2 or >2.6 millimoles/L(mmol/L)(calcium),<66 or >112 upper limit of normal mmol/L(creatinine), <3.5 or >5.1 mmol/L (potassium),<0.6 or >1 mmol/L (magnesium),<0.87 or >1.45mmol/L (phosphate),<63 or >83 g/L (protein),<135 or >145 mmol/L (sodium), <0.0 or >5.0 mg/L (C-reactive protein). Participants were counted in worst case category that their value changes to(low, within range [WR] or no change[NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became WR, were recorded in To WR or NC category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Up to Week 9
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected for analysis of occult blood, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood and protein can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Up to Week 12
Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Up to Week 9
Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Up to Week 9
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury [mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), pulse rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <10(low) or >25(high) and body temperature (degrees Celsius) <35 (low) or >38 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Up to Week 9
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Abnormal findings were categorized as CS and not NCS. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Up to 24 hours post-dose
Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Up to 24 hours post-dose
Part B: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Up to 24 hours post-dose
Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899. Predicted accumulation ratio is calculated as 1/(1-e^[k*tau]) where k is elimination rate constant following the single dose and tau is the dosing interval for the intended repeat dosing.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Cmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Tmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: T1/2 After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were planned to be collected at indicated time points for PK analysis.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau
Blood samples were planned to be collected at indicated time points for PK analysis.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of AUC(0-tau) at Day 10 to AUC(0-tau) at Day 1.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Cmax at Day 10 to Cmax at Day 1.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Ctau at Day 10 to Ctau at Day 1.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC
Blood samples were planned to be collected at indicated time points for PK analysis. Time-invariance ratio was planned to be calculated as AUC(0-12) on Day 10 to AUC(0-infinity) on Day 1.
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
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FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
0 subjects
FG0041 subjects
FG0052 subjects
FG0061 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0052 subjects
FG0061 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0042 subjectsNew participant enrolled and dosed.
FG0052 subjects
FG0062 subjectsNew participant enrolled and dosed.
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Safety Population Consisted of All Randomized Participants Who Received at Least 1 Dose of Treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0042 subjects
FG0052 subjects
FG0062 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0042 subjects
FG0052 subjects
FG0062 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0042 subjects
FG0052 subjects
FG0062 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
BG001
Part A:Cohort 1-GSK3186899 30 mg/60 mg/Placebo/300 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
BG002
Part A:Cohort 1-GSK3186899 30 mg/Placebo/120 mg/300 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
BG003
Part A:Cohort 1-Placebo/GSK3186899 60 mg/120 mg/300 mg
Participants in Part A Cohort 1 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3; further followed by a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
BG004
Part A:Cohort 2-GSK3186899 300 mg/600 mg/800 mg/Placebo
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by a single dose of Placebo on Day 1 in treatment Period 4. There was a washout period of 10 days between each treatment period.
BG005
Part A:Cohort 2-GSK3186899 300 mg/600 mg/Placebo/Dose Level 7
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of Placebo on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
BG006
Part A:Cohort 2-GSK3186899 300 mg/Placebo/800 mg/Dose Level 7
Participants in Part A Cohort 2 received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 1; followed by a single dose of Placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
BG007
Part A:Cohort 2-Placebo/GSK3186899 600 mg/800 mg/Dose Level 7
Participants in Part A Cohort 2 received a single dose of Placebo on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3; further followed by dose level 7 was planned to receive on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended. There was a washout period of 10 days between each treatment period.
BG008
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
BG009
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
BG010
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
BG011
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
BG012
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
BG013
Total
Total of all reporting groups
3
BG0012
BG0022
BG0034
BG0044
BG0053
BG0063
BG0073
BG0080
BG0090
BG0100
BG0110
BG0120
BG01324
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00044.7± 6.51
BG00134.0± 1.41
BG00233.0± 8.49
BG00331.3± 8.77
BG00434.5± 13.20
BG00537.3± 4.04
BG00639.7± 8.50
BG00741.0± 10.54
BG01336.9± 8.76
Sex: Female, Male
Baseline characteristics were reported for Safety Population which consisted of all randomized participants who received at least one dose of study treatment.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0130
Male
BG0003
BG0012
BG0022
BG0034
BG004
Race/Ethnicity, Customized
Baseline characteristics were reported for Safety Population which consisted of all randomized participants who received at least one dose of study treatment.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian - Central/South Asian Heritage
BG0000
BG0010
BG0021
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0131
Asian - South East Asian Heritage
BG0000
BG0010
BG0020
BG0030
BG004
White - White/Caucasian/European Heritage
BG0003
BG0012
BG0021
BG0033
BG004
Black or African American
BG0000
BG0010
BG0020
BG0030
BG004
Mixed Race
BG0000
BG0010
BG0020
BG0031
BG004
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG0036
OG00412
OG0056
OG0066
OG0070
Title
Denominators
Categories
Non-SAEs
Title
Measurements
OG0005
OG0011
OG0022
OG0033
OG0045
OG0052
OG0063
SAEs
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Non-SAEs and SAEs
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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
PCI ranges were <0.0 or >0.1*10^9 cells per(/)liter(L)(basophils), <37 or >50 proportion of red blood cells(RBC) in blood(hematocrit),<130 or >170 grams/L(hemoglobin[Hb]), <1.2 or >3.65*10^9cells(c)/L (lymphocytes),<0.2 or >1*10^9c/L(monocytes), <2 or >7.5*10^9c/L(neutrophils), <150 or >400*10^9 c/L(platelets), <3.0 or >10*10^9c/L(white blood cell[WBC]count), <4.4 or >5.8*10^12 c/L(RBC count), <80 or >99 femtoliter(mean corpuscular[MC] volume), <26.0 or >33.5 picogram(MC Hb), <0.0 or >0.4*10^9 c/L(eosinophils). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became within range, were recorded in To within Range or No Change category.Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100 percentage(%).
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
Basophils: To low
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
PCI ranges were <34 or >50 grams/L(albumin),<40 or >129 international units/L[IU/L](alkaline phosphatase),<10 or >50 IU/L(alanine aminotransferase),<0 or >37(aspartate aminotransferase), <0 or >20 micromoles(mcmol)/L (direct bilirubin),<0 or >20 mcmol/L(bilirubin), <2.2 or >2.6 millimoles/L(mmol/L)(calcium),<66 or >112 upper limit of normal mmol/L(creatinine), <3.5 or >5.1 mmol/L (potassium),<0.6 or >1 mmol/L (magnesium),<0.87 or >1.45mmol/L (phosphate),<63 or >83 g/L (protein),<135 or >145 mmol/L (sodium), <0.0 or >5.0 mg/L (C-reactive protein). Participants were counted in worst case category that their value changes to(low, within range [WR] or no change[NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became WR, were recorded in To WR or NC category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
Albumin: To low
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected for analysis of occult blood, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood and protein can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
Occult blood
Title
Measurements
OG0001
OG0010
OG0020
OG003
Primary
Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
Abnormal - not clinically significant
Title
Measurements
OG0002
OG0011
OG0021
OG003
Primary
Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury [mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), pulse rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <10(low) or >25(high) and body temperature (degrees Celsius) <35 (low) or >38 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to Week 12
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
SBP: To Low
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to Week 9
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to Week 9
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Abnormal findings were categorized as CS and not NCS. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Count of Participants
Participants
Up to 24 hours post-dose
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- Placebo
Participants in Part A Cohorts 1 and 2 received a single dose of placebo on Day 1 in either treatment Periods 1, 2, 3 and 4.
OG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG00014
OG0016
OG0026
OG003
Title
Denominators
Categories
Abnormal - not clinically significant
Title
Measurements
OG0003
OG0010
OG0023
OG003
Primary
Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Up to 24 hours post-dose
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Primary
Part B: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Safety Population. Data was not collected as no participants were enrolled in Part B.
Posted
Up to 24 hours post-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3186899. PK Population consisted of all participants in the Safety Population who received at least 1 non-missing PK assessment.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol.Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Mean
Standard Deviation
Nanogram per milliliter
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Pre-dose
Title
Measurements
OG0000.000± 0.0000
OG0010.000± 0.0000
OG0020.000± 0.0000
OG003
Secondary
Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hours*nanogram per milliliter
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG000725.40± 41.62
OG0011597.85± 32.30
OG0025268.31± 31.32
OG003
Secondary
Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hours*nanogram per milliliter
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG000739.13± 42.31
OG0011607.27± 32.10
OG0025287.60± 31.20
OG003
Secondary
Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanogram per milliliter
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG000239.206± 34.38
OG001356.232± 19.32
OG0021214.000± 29.72
OG003
Secondary
Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Median
Full Range
Hour
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.00(0.5 to 1.5)
OG0013.00(1.0 to 3.0)
OG0021.00(1.0 to 1.5)
OG003
Secondary
Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected for this endpoint as it was incorrectly stated as one of the Secondary Endpoint in Objectives and Endpoints section of the Protocol, where the reference to Ctau for single ascending dose part was an error. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was planned to be presented in a single arm because of similar dosing strategies as pre-defined in the protocol.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Median
Full Range
Hour
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.982(1.44 to 2.44)
OG0012.955(1.66 to 3.50)
OG0022.758(2.58 to 3.93)
OG003
Secondary
Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899. Predicted accumulation ratio is calculated as 1/(1-e^[k*tau]) where k is elimination rate constant following the single dose and tau is the dosing interval for the intended repeat dosing.
PK Population. Only those participants with data available at the specified time points were analyzed. Data for Part A: Cohorts 1 and 2- GSK3186899 300 mg arm was presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Mean
Standard Deviation
Ratio
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
OG001
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
OG002
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
OG003
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
OG004
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
OG005
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
OG006
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.0183± 0.01324
OG0011.0631± 0.03952
OG0021.0704± 0.04505
OG003
Secondary
Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Cmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Tmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: T1/2 After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
PK Population. Only those participants with data available at the specified time points were analyzed. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Number
90% Confidence Interval
Slope of log dose
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- GSK3186899 30 to 800 mg
Participants in Part A received a single dose of GSK3186899 30, 60, 120, 300, 600 and 800 mg in any of the treatment Periods of Cohorts 1 or 2 according to randomization schedule.
Units
Counts
Participants
OG00022
Title
Denominators
Categories
Title
Measurements
OG0001.47(1.34 to 1.61)
Secondary
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were planned to be collected at indicated time points for PK analysis.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
PK Population. Only those participants with data available at the specified time points were analyzed. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
Posted
Number
90% Confidence Interval
Slope of log dose
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohorts 1 and 2- GSK3186899 30 to 800 mg
Participants in Part A received a single dose of GSK3186899 30, 60, 120, 300, 600 and 800 mg in any of the treatment Periods of Cohorts 1 or 2 according to randomization schedule.
Units
Counts
Participants
OG00022
Title
Denominators
Categories
Title
Measurements
OG0001.19(1.09 to 1.30)
Secondary
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
PK Population. Data was not collected as no participants were enrolled in Part A Cohort 3.
Posted
Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
ID
Title
Description
OG000
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
OG001
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
Units
Counts
Participants
OG0000
OG0010
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau
Blood samples were planned to be collected at indicated time points for PK analysis.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of AUC(0-tau) at Day 10 to AUC(0-tau) at Day 1.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Cmax at Day 10 to Cmax at Day 1.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Ctau at Day 10 to Ctau at Day 1.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC
Blood samples were planned to be collected at indicated time points for PK analysis. Time-invariance ratio was planned to be calculated as AUC(0-12) on Day 10 to AUC(0-infinity) on Day 1.
PK Population. Data was not collected as no participants were enrolled in Part B.
Posted
Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
ID
Title
Description
OG000
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG001
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
OG002
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
Units
Counts
Participants
OG0000
OG0010
OG0020
0
14
0
14
5
14
EG001
Part A: Cohort 1- GSK3186899 30 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 30 mg on Day 1 in treatment Period 1.
0
6
0
6
1
6
EG002
Part A: Cohort 1- GSK3186899 60 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 60 mg on Day 1 in treatment Period 2.
0
6
0
6
2
6
EG003
Part A: Cohort 1- GSK3186899 120 mg
Participants in Part A Cohort 1 received a single dose of GSK3186899 120 mg on Day 1 in treatment Period 3.
0
6
0
6
3
6
EG004
Part A: Cohorts 1 and 2- GSK3186899 300 mg
Participants in Part A received a single dose of GSK3186899 300 mg on Day 1 in treatment Period 4 of Cohort 1 and treatment Period 1 of Cohort 2.
0
12
0
12
5
12
EG005
Part A: Cohort 2- GSK3186899 600 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 600 mg on Day 1 in treatment Period 2.
0
6
0
6
2
6
EG006
Part A: Cohort 2- GSK3186899 800 mg
Participants in Part A Cohort 2 received a single dose of GSK3186899 800 mg on Day 1 in treatment Period 3.
0
6
0
6
3
6
EG007
Part A: Cohort 2- GSK3186899 Dose Level 7
Participants in Part A Cohort 2 were planned to receive dose level 7 on Day 1 in treatment Period 4. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.
0
0
0
0
0
0
EG008
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
0
0
0
0
0
0
EG009
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)
Participants in Part A Cohort 3 were planned to receive a single dose of GSK3186899 under fed conditions on Day 1 in treatment Period 1; followed by a single dose of GSK3186899 under fasted conditions on Day 1 in treatment Period 2. There was a planned washout period of 10 days between each treatment period.
0
0
0
0
0
0
EG010
Part B: Cohort 4- GSK3186899 or Placebo
Participants in Part B Cohort 4 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
0
0
0
0
0
0
EG011
Part B: Cohort 5- GSK3186899 or Placebo
Participants in Part B Cohort 5 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
0
0
0
0
0
0
EG012
Part B: Cohort 6- GSK3186899 or Placebo
Participants in Part B Cohort 6 were planned to receive repeat dose of GSK3186899 or placebo on Days 1 to 10.
0
0
0
0
0
0
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Nausea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Vomiting
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Medical device site dermatitis
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Medical device site reaction
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Chest pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Nasopharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0052 events2 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Taste disorder
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Tachycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Limb injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Aspartate aminotransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Blood creatine phosphokinase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Hepatic enzyme increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Abnormal dreams
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected14 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected12 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected0 at risk
EG0080 events0 affected0 at risk
EG0090 events0 affected0 at risk
EG0100 events0 affected0 at risk
EG0110 events0 affected0 at risk
EG0120 events0 affected0 at risk
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.