Safety, Tolerability, Pharmacokinetics, and Pharmacodynam... | NCT03245619 | Trialant
NCT03245619
Sponsor
GlaxoSmithKline
Status
Terminated
Last Update Posted
Jun 16, 2020Actual
Enrollment
18Actual
Phase
Phase 1
Conditions
Pancreatitis, Acute Necrotizing
Interventions
GSK3335065
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
NCT03245619
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
201570
Secondary IDs
ID
Type
Description
Link
2016-001303-22
EudraCT Number
Brief Title
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults
Official Title
Randomized, Double-blind, Placebo Controlled Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses (Intravenous Bolus) and Constant Intravenous Infusion Over 7 Days of GSK3335065 in Healthy Adult Subjects
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
Jun 2020
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was terminated as relationship between GSK3335065 and ventricular tachycardia could not be excluded.
Expanded Access Info
No
Start Date
Aug 22, 2017Actual
Primary Completion Date
May 19, 2018Actual
Completion Date
May 19, 2018Actual
First Submitted Date
Aug 7, 2017
First Submission Date that Met QC Criteria
Aug 7, 2017
First Posted Date
Aug 10, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Jun 17, 2019
Results First Submitted that Met QC Criteria
Aug 20, 2019
Results First Posted Date
Sep 20, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 12, 2020
Last Update Posted Date
Jun 16, 2020Actual
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
GSK3335065 is being developed as a treatment for acute pancreatitis with the intent of reducing 3-hydroxykynurenine (3HK) levels to the normal range (or lower) and maintaining them at this level throughout the treatment period. This study will utilize an adaptive design and is divided into 3 parts. Part A will consist of 8 cohorts (1-8) and is Single Ascending Dose (SAD) of GSK3335065 by IV bolus in males. Part B will be initiated after completion of dosing in Part A. It will involve ascending IV bolus doses of GSK3335065 followed by IV constant infusion for 7 days in males and will consist of four cohorts (9-12). Part C consists of a single dose of GSK3335065 by IV bolus (cohort 13), and a single dose followed by continuous infusion over 7 days (cohort 14) in females of non-child bearing potential (WONCBP). Total 64 subjects will be evaluated in the study of which Part A will include 16 healthy male subjects, Part B will include 32 healthy male subjects and Part C will include 16 WONCBP. In Part A, cohorts 1 and 2 will last up to 19 weeks and cohorts 3 to 8 will last up to 7 weeks and Part B will last up to 13 weeks. In Part C cohort 7 will last up to 7 weeks and cohort 8 will last for 13 weeks.
Detailed Description
Not provided
Conditions Module
Conditions
Pancreatitis, Acute Necrotizing
Keywords
3-hydroxykynurenine
Acute pancreatitis
Dose-escalation
Healthy subjects
GSK3335065
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
18Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A
Experimental
Male subjects will be assigned to Cohorts 1 to 8. In each cohort, six subjects will be randomized to receive alternating and escalated doses of GSK3335065.
Drug: GSK3335065
Subjects receiving Placebo (Cohorts 1 to 8) in Part A
Experimental
Male subjects will be assigned to Cohort 1 and 2. In each cohort, two subjects will be randomized to receive placebo.
Drug: Placebo
Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B
Experimental
Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, six subjects will be randomized to receive GSK3335065. In all cohorts each dose level will consist of an IV bolus on Day 1 subsequently followed by a continuous IV infusion for seven days.
Drug: GSK3335065
Subjects receiving Placebo (Cohort 9 to 12) in Part B
Experimental
Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, two subjects will be randomized to receive placebo.
Drug: Placebo
Subjects receiving GSK3335065 (Cohort 13) in Part C
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
GSK3335065
Drug
GSK3335065 is being developed as a treatment for acute pancreatitis with the intent of reducing 3-hydroxykynurenine (3HK) levels to the normal range (or lower) and maintaining them at this level. GSK3335065 is a solution and will be administered as intravenous injection and infusion with dose strength of 5 milligram (mg)/mL that may be diluted in 0.9% weight by volume (w/v) sodium chloride.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With AEs and SAEs-Part B
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Up to Day 34
Number of Participants With AEs and SAEs-Part C
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Secondary Outcomes
Measure
Description
Time Frame
Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-t]) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic (PK) analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. PK Parameter Population comprised of all active participants whose PK sample was obtained and analyzed and who provided PK parameters.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria
Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent. In Part C (WONCBP) subjects must be between 18 and 60 years of age.
Subjects who are overtly healthy as determined by 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 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 greater than 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m^2).
Length of time required for abstinence or use of contraceptives should take into account the reproductive toxicity profile including genotoxicity and teratogenicity, the size of the molecule, and the number of doses. Male subjects must agree to use contraception during the treatment period and for at least 2 days after the last dose of study treatment and refrain from donating sperm during this period. Only female subjects of WONCBP are eligible to participate.
Capable of giving signed informed consent.
Exclusion Criteria
ALT and bilirubin greater than 1.5 times upper limit of normal (ULN) (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
QTc corrected by Fridericia's formula(QTcF) greater than 450 millisecond (msec) from a mean of triplicate readings taken 5 mins apart
Clinically significant abnormal echocardiogram
The subject has a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt
Cardiac troponin (cTn) or Brain natriuretic peptide (BNP) greater than ULN
Use of prohibited medication
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).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
A positive pre-study drug/alcohol screen
A positive test for human immunodeficiency virus (HIV) antibody
Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 84 days.
Poor or unsuitable venous access
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
History of smoking within 6 months of the study.
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
60 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 0GG
United Kingdom
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
A total of 55 participants were screened of which 33 failed screening and 4 were kept in reserve but not used. A total of 18 participants were enrolled in the study. The study was conducted in the United Kingdom. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Recruitment Details
This was planned to be a 3 part, dose escalation study; however, the study was terminated during Part A (Cohort 3) because a relationship between GSK3335065 and ventricular tachycardia in a participant could not be excluded. Hence, participants were not recruited in Cohorts 4 to 8 of Part A; Part B and Part C were not initiated.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
FG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
FG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
FG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
FG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
FG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
FG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
FG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
FG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
FG009
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
FG010
Part B-Cohort 9: 0.14 mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.012 mg/hour for 7 days.
FG011
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
FG012
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
FG013
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
FG014
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
FG015
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
FG016
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Periods
Title
Milestones
Reasons Not Completed
Part A (Up to Day 22)
Type
Comment
Milestone Data
STARTED
FG0005 subjects
FG0016 subjects
FG0026 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
NOT COMPLETED
FG0004 subjects
FG0016 subjects
FG0026 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Physician Decision
FG0004 subjects
FG0016 subjects
FG0026 subjects
FG003
Part B (Up to 34 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part C (Up to 34 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
The study was terminated during Part A-Cohort 3; hence, no participants were enrolled in Part A (Cohorts 4 to 8), Part B and Part C.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
BG001
Part A-Cohort 1: GSK3335065 0.1 mg
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
Mean
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
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
Adverse Events Module
Frequency Threshold
0
Time Frame
Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3).
Description
AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
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: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Tachycardia
Cardiac disorders
MedDRA 21.1
Systematic Assessment
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Headache
Nervous system disorders
MedDRA 21.1
Systematic Assessment
More Info Module
Limitations and Caveats
Due to sample handling errors at clinical site, reported results (3HK/Kyn) in Cohort 3 are characterized by a consistent negative bias; therefore must not be compared with concentration data from Cohort 1 or 2.
WONCBP will be assigned to cohort 13. Six subjects will be randomized to receive a single IV dose of GSK3335065.
Drug: GSK3335065
Subjects receiving Placebo (Cohort 13) in Part C
Experimental
WONCBP will be assigned to cohort 13. Two subjects will be randomized to receive placebo.
Drug: Placebo
Subjects receiving GSK3335065 (Cohort 14) in Part C
Experimental
WONCBP will be assigned to cohort 14. Six subjects will be randomized to receive a continuous IV infusion over 7 days of GSK3335065.
Drug: GSK3335065
Subjects receiving Placebo (Cohort 14) in Part C
Experimental
WONCBP will be assigned to cohort 14. Two subjects will be randomized to receive placebo.
Drug: Placebo
Subjects receiving GSK3335065 (Cohort 13) in Part C
Subjects receiving GSK3335065 (Cohort 14) in Part C
Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B
Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A
Placebo
Drug
Placebo solution to match GSK3335065 will be given as intravenous injection and infusion.
Subjects receiving Placebo (Cohort 13) in Part C
Subjects receiving Placebo (Cohort 14) in Part C
Subjects receiving Placebo (Cohort 9 to 12) in Part B
Subjects receiving Placebo (Cohorts 1 to 8) in Part A
Up to Day 34
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A
Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8x10^9 cells per liter [cells/L]); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of hematology parameters.
Up to Day 34
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of hematology parameters.
Up to Day 34
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: <30 millimoles per liter [mmol/L]); alanine aminotransferase (ALT) (high: >=2xupper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2xULN); alkaline phosphatase (ALP) (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Up to Day 34
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Up to Day 34
Number of Participants With Abnormal Urine Parameters-Part A
Urine samples were taken for the assessment of following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed and collected for any abnormal dipstick results. Number of participants with abnormal urine parameters any time post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With Abnormal Urine Parameters-Part B
Urine samples were planned to be collected for the assessment of urine parameters.
Up to Day 34
Number of Participants With Abnormal Urine Parameters-Part C
Urine samples were planned to be collected for the assessment of urine parameters.
Up to Day 34
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A
Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF) and Bazett's QT interval corrected for heart rate (QTcB). ECG measurements were preceded by at least 5 minutes rest for the participant in a semi-recumbent position. Number of participants with abnormal-clinically significant and abnormal-not clinically significant ECG findings at worst case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With Abnormal ECG Findings-Part B
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Up to Day 34
Number of Participants With Abnormal ECG Findings-Part C
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Up to Day 34
Number of Participants With Abnormal Vital Signs-Part A
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiration rate and temperature were measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Participants are counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Data for worst case post-Baseline relative to Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Up to Day 22
Number of Participants With Abnormal Vital Signs-Part B
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Up to Day 34
Number of Participants With Abnormal Vital Signs-Part C
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Maximum Observed Concentration (Cmax) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Time to Reach Maximum Concentration (Tmax) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Volume of Distribution for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Volume of Distribution for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Apparent Terminal Half Life (T1/2) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohort 1 and 2)
Blood samples were collected to measure the kynurenine-3-monooxygenase (KMO) enzyme inhibition by determining the levels of the biomarkers Kynurenine (Kyn) and 3-hydroxykynurenine (3-HK). Baseline was the average of all pre-dose measurements (Day 1 [pre-dose at 1 hour and 30 minutes]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohorts 3 to 8)
Blood samples were collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK. Baseline was the average of all pre-dose measurements (Day -1 [pre-dose at 16 hours, 14 hours, 12 hours and 10 hours] and Day 1 [pre-dose at 30 minutes and 2 hours]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
BG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
BG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
BG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
BG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
BG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
BG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
BG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
BG009
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
BG010
Part B-Cohort 9: 0.14 mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.012 mg/hour for 7 days.
BG011
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
BG012
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
BG013
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
BG014
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
BG015
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
BG016
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
BG017
Total
Total of all reporting groups
5
BG0016
BG0026
BG0031
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0130
BG0140
BG0150
BG0160
BG01718
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00041.8± 5.97
BG00135.8± 11.81
BG00243.2± 7.57
BG00347.0± NAStandard deviation could not be calculated as only one participant was analyzed.
BG01740.6± 8.91
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0130
BG0140
BG0150
BG0160
BG0170
Male
BG0005
BG0016
BG0026
BG0031
BG004
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
African American/African Heritage
BG0001
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0130
BG0140
BG0150
BG0160
BG0171
White-White/Caucasian/European Heritage
BG0004
BG0016
BG0026
BG0031
BG004
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG0031
OG0040
OG0050
OG0060
OG0070
OG0080
Title
Denominators
Categories
Any AE
Title
Measurements
OG0003
OG0014
OG0023
OG0031
Any SAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With AEs and SAEs-Part B
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With AEs and SAEs-Part C
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A
Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood); hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8x10^9 cells per liter [cells/L]); neutrophil count (low: <1.5x10^9 cells/L); platelet count (low: <100x10^9 cells/L and high: >550x10^9 cells/L); white blood cells count (low: <3x10^9 cells/L and high: >20x10^9 cells/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
Hemoglobin; Normal
Title
Measurements
OG0005
OG0016
OG0026
OG003
Primary
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of hematology parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of hematology parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: <30 millimoles per liter [mmol/L]); alanine aminotransferase (ALT) (high: >=2xupper limit of normal [ULN]); aspartate aminotransferase (AST) (high: >=2xULN); alkaline phosphatase (ALP) (high: >=2xULN); total bilirubin (high: >=1.5xULN); calcium (low: <2 mmol/L and high: >2.75 mmol/L); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
Albumin; Low
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Number of Participants With Abnormal Urine Parameters-Part A
Urine samples were taken for the assessment of following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed and collected for any abnormal dipstick results. Number of participants with abnormal urine parameters any time post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0021
OG003
Primary
Number of Participants With Abnormal Urine Parameters-Part B
Urine samples were planned to be collected for the assessment of urine parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Abnormal Urine Parameters-Part C
Urine samples were planned to be collected for the assessment of urine parameters.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A
Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF) and Bazett's QT interval corrected for heart rate (QTcB). ECG measurements were preceded by at least 5 minutes rest for the participant in a semi-recumbent position. Number of participants with abnormal-clinically significant and abnormal-not clinically significant ECG findings at worst case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
Abnormal-clinically significant
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Abnormal ECG Findings-Part B
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Abnormal ECG Findings-Part C
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Primary
Number of Participants With Abnormal Vital Signs-Part A
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiration rate and temperature were measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Participants are counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Data for worst case post-Baseline relative to Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Posted
Count of Participants
Participants
Up to Day 22
ID
Title
Description
OG000
Part A: Placebo
Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.
OG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
OG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
OG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
OG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
OG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
OG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
DBP; To Low
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Abnormal Vital Signs-Part B
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Primary
Number of Participants With Abnormal Vital Signs-Part C
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.
Posted
Up to Day 34
ID
Title
Description
OG000
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-t]) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic (PK) analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. PK Parameter Population comprised of all active participants whose PK sample was obtained and analyzed and who provided PK parameters.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0006
OG0016
Title
Denominators
Categories
Title
Measurements
OG00014.1222± 576.3
OG001201.1366± 30.9
Secondary
AUC(0-t) for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
AUC(0-t) for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
AUC(0-t) for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
PK Parameter Population. Only participants with PK parameters that could be derived are summarized.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0001
OG0014
Title
Denominators
Categories
Title
Measurements
OG00051.68± NAGeometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
OG001310.46± 26.2
Secondary
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
AUC(0-Inf) for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
AUC(0-Inf) for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0006
OG0016
Title
Denominators
Categories
Title
Measurements
OG0009.0006(0.333 to 71.700)
OG00172.0250(72.000 to 72.100)
Secondary
Tlast of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Tlast of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
Tlast of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Maximum Observed Concentration (Cmax) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0006
OG0016
Title
Denominators
Categories
Title
Measurements
OG00010.018± 145.8
OG00114.254± 37.6
Secondary
Cmax of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Cmax of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
Cmax of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Time to Reach Maximum Concentration (Tmax) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0006
OG0016
Title
Denominators
Categories
Title
Measurements
OG0000.2050(0.200 to 0.500)
OG0010.2061(0.200 to 0.217)
Secondary
Tmax of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Tmax of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
Tmax of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Clearance for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
PK Parameter Population. Only participants with PK parameters that could be derived are summarized.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0001
OG0014
Title
Denominators
Categories
Title
Measurements
OG0001.9349± NAGeometric coefficient of variation could not be calculated as only one participant was analyzed.
OG0010.8053± 26.2
Secondary
Clearance for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Clearance for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
Clearance for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Volume of Distribution for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
PK Parameter Population. Only participants with PK parameters that could be derived are summarized.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0001
OG0014
Title
Denominators
Categories
Title
Measurements
OG0002.074± NAGeometric coefficient of variation could not be calculated as only one participant was analyzed.
OG00144.642± 43.0
Secondary
Volume of Distribution for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Volume of Distribution for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
Volume of Distribution for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Apparent Terminal Half Life (T1/2) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
PK Parameter Population. Only participants with PK parameters that could be derived are summarized.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
Units
Counts
Participants
OG0001
OG0014
Title
Denominators
Categories
Title
Measurements
OG0000.515(0.515 to 0.515)
OG00134.4957(31.458 to 49.278)
Secondary
T1/2 for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG001
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG002
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG003
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
T1/2 for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
Units
Counts
Participants
OG0000
Secondary
T1/2 for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
Secondary
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohort 1 and 2)
Blood samples were collected to measure the kynurenine-3-monooxygenase (KMO) enzyme inhibition by determining the levels of the biomarkers Kynurenine (Kyn) and 3-hydroxykynurenine (3-HK). Baseline was the average of all pre-dose measurements (Day 1 [pre-dose at 1 hour and 30 minutes]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
All Subject Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). Data was not collected for placebo arms of Cohorts 1 and 2.
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
OG001
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
OG002
Part A-Cohort 1: Placebo
Healthy male participants were administered a single IV bolus dose of GSK3335065 matching placebo on Day 1.
OG003
Part A-Cohort 2: Placebo
Healthy male participants were administered a single IV bolus dose of GSK3335065 matching placebo on Day 1.
Units
Counts
Participants
OG0006
OG0016
OG0020
OG003
Title
Denominators
Categories
3-HK, 6 minutes, n=6, 6,0,0
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0020
ParticipantsOG003
Secondary
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohorts 3 to 8)
Blood samples were collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK. Baseline was the average of all pre-dose measurements (Day -1 [pre-dose at 16 hours, 14 hours, 12 hours and 10 hours] and Day 1 [pre-dose at 30 minutes and 2 hours]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled. Only those participants with data available at the specified time points were analyzed.
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
OG001
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
OG002
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
OG003
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
OG004
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
OG003
Secondary
Change From Baseline in Levels of Tryptophan Metabolites-Part C
Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.
All Subject Population. Data was not collected as no participants were enrolled in Part C of the study.
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
OG001
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
OG002
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Units
Counts
Participants
OG0000
OG0010
OG0020
0
5
0
5
3
5
EG001
Part A-Cohort 1: GSK3335065 0.1 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.
0
6
0
6
4
6
EG002
Part A-Cohort 2: GSK3335065 0.25 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.
0
6
0
6
3
6
EG003
Part A-Cohort 3: GSK3335065 1.3 mg
Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
0
1
1
1
1
1
EG004
Part A-Cohort 4: GSK335065 2.6 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.
0
0
0
0
0
0
EG005
Part A-Cohort 5: GSK335065 5.5 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.
0
0
0
0
0
0
EG006
Part A-Cohort 6: GSK335065 12 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.
0
0
0
0
0
0
EG007
Part A-Cohort 7: GSK335065 35 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.
0
0
0
0
0
0
EG008
Part A-Cohort 8: GSK335065 54 mg
Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
0
0
0
0
0
0
EG009
Part B: Placebo
Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.
0
0
0
0
0
0
EG010
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.
0
0
0
0
0
0
EG011
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.
0
0
0
0
0
0
EG012
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.
0
0
0
0
0
0
EG013
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.
0
0
0
0
0
0
EG014
Part C: Placebo
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.
0
0
0
0
0
0
EG015
Part C-Cohort 13: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.
0
0
0
0
0
0
EG016
Part C-Cohort 14: GSK3335065
Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.