Healthy Volunteers
Conditions
Keywords
GSK2330811, Healthy participants, Japanese, Pharmacokinetics, Safety, Subcutaneous dose
Brief summary
This is a randomized, double-blind (sponsor-open), placebo-controlled, single-center study involving Japanese participants. The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after a single subcutaneous (SC) dose of GSK2330811 in healthy Japanese participants. GSK2330811 is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds and inhibits the action of Oncostatin M (OSM) and is being developed for the treatment of Crohn's disease (CD) and Systemic sclerosis (SSc). Participants will be randomized to receive either GSK2330811 (450 milligram \[mg\]) or placebo in an approximate ratio of 7:3.
Interventions
DRUGPlacebo
Placebo is 0.9 percent sodium chloride solution. It will be administered as SC injection to abdomen by study personnel. Three injections will be used to match active doses.
DRUGGSK2330811
GSK2330811 will be available as SC injection 150 mg/mL.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a parallel group study. Participants will be randomized to receive either GSK2330811 (450 mg) or placebo in an approximate ratio of 7:3.
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECGs. * A participant with a clinical abnormality or laboratory parameters outside the reference range for the healthy population being studied that is not specifically listed in the inclusion or
Exclusion criteria
may be included if the investigator and sponsor medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or interpretation. * Participants with body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 18.5-29.9 kg per square meter. * Male participants. * Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * Participants with Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Participants should have lived outside Japan for less than 10 years at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 126 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment. Safety Population consisted of all randomized participants who received at least one dose of study treatment. |
| Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | Baseline (Pre-dose, Day 1) and up to Day 126 | Vital signs were measured in semi-supine position after 5 minutes of rest and included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Participants were counted in the worst case category that their value changed to low, within range or high, unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the Within Range or No Change category. Participants were counted twice if values changed 'To Low' and 'To High', so the percentages were not added up to 100 percent (%). Participants with missing Baseline values were assumed as within range value. PCI ranges were: SBP (lower: \<85, upper: \>160 millimeter of mercury \[mmHg\]); DBP (lower: \<45, upper: \>100 mmHg); HR (lower: \<40, upper: \>110 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. |
| Change From Baseline in Body Temperature | Baseline (Pre-dose, Day 1), Day 1: 1, 4, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings | Up to Day 126 | 12-lead ECGs were recorded in semi-supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Up to Day 126 | Blood samples were collected for the analysis of clinical chemistry parameters. Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Clinical chemistry parameters included: total bilirubin, calcium, creatinine and triglycerides. |
| Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Baseline (Pre-dose, Day 1) and up to Day 126 | Blood samples were collected for the analysis of the following hematology parameters: hemoglobin (Hb), lymphocytes (Lympho), platelet count (PC), neutrophil count (Neutro) and White Blood Cell count (WBC). The laboratory parameters were graded according to NCI-CTCAE version 5.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severity. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. An increase was defined as an increase in CTCAE Grade relative to Baseline Grade. |
| Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Baseline (Pre-dose, Day 1) and up to Day 126 | Urine samples were collected for analysis of blood, glucose, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hemoglobin Nadir for GSK2330811 | Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin. Time to nadir was defined as Study Day of Nadir minus 1. |
| Number of Participants With Positive Anti-GSK2330811 Antibodies | Up to Day 126 | Serum samples were analyzed for the presence of anti-GSK2330811 antibodies using an antibody binding assay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Number of participants with confirmed positive anti-GSK2330811 antibodies are presented. |
| Maximum Plasma Concentration (Cmax) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. Pharmacokinetic Population consisted of all participants in the Safety population who received at least one active dose of study treatment and had at least 1 non-missing PK assessment. |
| Time to Platelet Count Nadir for GSK2330811 | Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count. Time to nadir was defined as Study Day of Nadir minus 1. |
| Hemoglobin Nadir for GSK2330811 | Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at the indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin. |
| Platelet Count Nadir for GSK2330811 | Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count. |
| Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
| Apparent Systemic Clearance (CL/F) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
| Time to Cmax (Tmax) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
| Terminal Half-life (t1/2) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
| Apparent Volume of Distribution at Steady State (Vss/F) for GSK2330811 | Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. |
Countries
United Kingdom
Participant flow
Recruitment details
This was a randomized, double-blind, placebo-controlled, single-center study with single subcutaneous (SC) dose of GSK2330811 administered in healthy male Japanese participants.
Pre-assignment details
A total of 9 participants were randomized and enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single SC dose of Placebo, administered as three separate SC injections. | 2 |
| GSK2330811 450 mg Participants received a single 450 milligram (mg) SC dose of GSK2330811, administered as three separate SC injections of 150 milligrams per milliliter \[mg/mL\]). | 7 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | GSK2330811 450 mg | Total |
|---|---|---|---|
| Age, Continuous | 21.0 Years STANDARD_DEVIATION 2.83 | 29.1 Years STANDARD_DEVIATION 6.52 | 27.3 Years STANDARD_DEVIATION 6.76 |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 2 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 7 |
| other Total, other adverse events | 2 / 2 | 6 / 7 |
| serious Total, serious adverse events | 0 / 2 | 0 / 7 |
Outcome results
Primary
Change From Baseline in Body Temperature
Body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose, Day 1), Day 1: 1, 4, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Temperature | Day 1: 1 hour, n=2,7 | 0.15 Degrees Celsius | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Body Temperature | Day 1: 4 hour, n=2,7 | 0.40 Degrees Celsius | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Body Temperature | Day 1: 8 hour, n=2,7 | 0.45 Degrees Celsius | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Body Temperature | Day 2: n=2,7 | -0.15 Degrees Celsius | Standard Deviation 0.919 |
| Placebo | Change From Baseline in Body Temperature | Day 3: n=2,7 | -0.30 Degrees Celsius | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Body Temperature | Day 5: n=2,7 | 0.20 Degrees Celsius | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Body Temperature | Day 7: n=2,7 | -0.30 Degrees Celsius | Standard Deviation 0.566 |
| Placebo | Change From Baseline in Body Temperature | Day 10: n=2,7 | -0.10 Degrees Celsius | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Body Temperature | Day 14: n=2,7 | 0.25 Degrees Celsius | Standard Deviation 0.495 |
| Placebo | Change From Baseline in Body Temperature | Day 21: n=2,7 | 0.05 Degrees Celsius | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Body Temperature | Day 28: n=2,7 | 0.20 Degrees Celsius | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Body Temperature | Day 42: n=2,7 | -0.60 Degrees Celsius | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Body Temperature | Day 56: n=2,6 | 0.00 Degrees Celsius | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Body Temperature | Day 84: n=1,6 | 0.90 Degrees Celsius | — |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 126: n=0,6 | 0.28 Degrees Celsius | Standard Deviation 0.595 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 10: n=2,7 | -0.10 Degrees Celsius | Standard Deviation 0.862 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 1: 1 hour, n=2,7 | 0.06 Degrees Celsius | Standard Deviation 0.237 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 42: n=2,7 | -0.10 Degrees Celsius | Standard Deviation 0.695 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 1: 4 hour, n=2,7 | 0.07 Degrees Celsius | Standard Deviation 0.287 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 14: n=2,7 | 0.21 Degrees Celsius | Standard Deviation 0.537 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 1: 8 hour, n=2,7 | 0.40 Degrees Celsius | Standard Deviation 0.346 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 84: n=1,6 | 0.30 Degrees Celsius | Standard Deviation 0.494 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 2: n=2,7 | -0.03 Degrees Celsius | Standard Deviation 0.486 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 21: n=2,7 | 0.09 Degrees Celsius | Standard Deviation 0.609 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 3: n=2,7 | -0.34 Degrees Celsius | Standard Deviation 0.336 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 56: n=2,6 | -0.03 Degrees Celsius | Standard Deviation 0.715 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 5: n=2,7 | -0.06 Degrees Celsius | Standard Deviation 0.8 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 28: n=2,7 | -0.06 Degrees Celsius | Standard Deviation 0.67 |
| GSK2330811 450 mg | Change From Baseline in Body Temperature | Day 7: n=2,7 | 0.09 Degrees Celsius | Standard Deviation 0.521 |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment. Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Time frame: Up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| GSK2330811 450 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters
Blood samples were collected for the analysis of the following hematology parameters: hemoglobin (Hb), lymphocytes (Lympho), platelet count (PC), neutrophil count (Neutro) and White Blood Cell count (WBC). The laboratory parameters were graded according to NCI-CTCAE version 5.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severity. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. An increase was defined as an increase in CTCAE Grade relative to Baseline Grade.
Time frame: Baseline (Pre-dose, Day 1) and up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 2 | 1 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 4 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 1 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 2 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 3 | 0 Participants |
| Placebo | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 1 | 3 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 2 | 2 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 1 | 3 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 2 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count decreased, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,WBC decreased, increase to Grade 2 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 1 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | WBC,Leukocytosis, increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho,Lympho count increased, increase to Grade 4 | 0 Participants |
Primary
Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters
Blood samples were collected for the analysis of clinical chemistry parameters. Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Clinical chemistry parameters included: total bilirubin, calcium, creatinine and triglycerides.
Time frame: Up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 1 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 1 | 2 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 1 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 1 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 1 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 1 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 1 | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Total Bilirubin, Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 1 | 5 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Triglycerides, Grade 2 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 3 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Creatinine, Grade 4 | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Higher Clinical Chemistry Parameters | Calcium, Grade 4 | 0 Participants |
Primary
Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were recorded in semi-supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 0 Participants |
| Placebo | Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings | Abnormal - not clinically significant | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Findings | Abnormal - clinically significant | 0 Participants |
Primary
Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
Urine samples were collected for analysis of blood, glucose, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Time frame: Baseline (Pre-dose, Day 1) and up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Blood | 1 Participants |
| Placebo | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
| Placebo | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 0 Participants |
| Placebo | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Protein | 2 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Blood | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Ketones | 1 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | Glucose | 0 Participants |
Primary
Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Vital signs were measured in semi-supine position after 5 minutes of rest and included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Participants were counted in the worst case category that their value changed to low, within range or high, unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the Within Range or No Change category. Participants were counted twice if values changed 'To Low' and 'To High', so the percentages were not added up to 100 percent (%). Participants with missing Baseline values were assumed as within range value. PCI ranges were: SBP (lower: \<85, upper: \>160 millimeter of mercury \[mmHg\]); DBP (lower: \<45, upper: \>100 mmHg); HR (lower: \<40, upper: \>110 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment.
Time frame: Baseline (Pre-dose, Day 1) and up to Day 126
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To Within Range or No Change | 2 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To high | 0 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To low | 0 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To low | 0 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To high | 0 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To Within Range or No Change | 2 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To Within Range or No Change | 2 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To high | 0 Participants |
| Placebo | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To low | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To high | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To low | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To Within Range or No Change | 7 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | SBP, To high | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To low | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To Within Range or No Change | 7 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | DBP, To high | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To low | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | HR, To Within Range or No Change | 7 Participants |
Secondary
Apparent Systemic Clearance (CL/F) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Systemic Clearance (CL/F) for GSK2330811 | 0.010 Liter per hour | Geometric Coefficient of Variation 22.1925 |
Secondary
Apparent Volume of Distribution at Steady State (Vss/F) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Volume of Distribution at Steady State (Vss/F) for GSK2330811 | 6.713 Liter | Geometric Coefficient of Variation 12.2891 |
Secondary
Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration Time-curve From Time Zero to Infinity (AUC[0-infinity]) for GSK2330811 | 45371065.201 Hours*nanogram per milliliter | Geometric Coefficient of Variation 22.1925 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2330811 | 43157791.065 Hours*nanogram per milliliter | Geometric Coefficient of Variation 22.8839 |
Secondary
Hemoglobin Nadir for GSK2330811
Blood samples were collected at the indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin.
Time frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hemoglobin Nadir for GSK2330811 | 136.0 Grams per liter | Standard Deviation 8.49 |
| GSK2330811 450 mg | Hemoglobin Nadir for GSK2330811 | 134.9 Grams per liter | Standard Deviation 6.69 |
Secondary
Maximum Plasma Concentration (Cmax) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis. Pharmacokinetic Population consisted of all participants in the Safety population who received at least one active dose of study treatment and had at least 1 non-missing PK assessment.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) for GSK2330811 | 63259.308 Nanogram per milliliter | Geometric Coefficient of Variation 14.929 |
Secondary
Number of Participants With Positive Anti-GSK2330811 Antibodies
Serum samples were analyzed for the presence of anti-GSK2330811 antibodies using an antibody binding assay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Number of participants with confirmed positive anti-GSK2330811 antibodies are presented.
Time frame: Up to Day 126
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Positive Anti-GSK2330811 Antibodies | 0 Participants |
| GSK2330811 450 mg | Number of Participants With Positive Anti-GSK2330811 Antibodies | 0 Participants |
Secondary
Platelet Count Nadir for GSK2330811
Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count.
Time frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Platelet Count Nadir for GSK2330811 | 211.5 Giga cells per liter | Standard Deviation 27.58 |
| GSK2330811 450 mg | Platelet Count Nadir for GSK2330811 | 79.1 Giga cells per liter | Standard Deviation 29.48 |
Secondary
Terminal Half-life (t1/2) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half-life (t1/2) for GSK2330811 | 469.117 Hours | Geometric Coefficient of Variation 14.8081 |
Secondary
Time to Cmax (Tmax) for GSK2330811
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2330811. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 8 hours; Days 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Cmax (Tmax) for GSK2330811 | 143.380 Hours |
Secondary
Time to Hemoglobin Nadir for GSK2330811
Blood samples were collected at indicated time points for analysis of hemoglobin nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the hemoglobin. Time to nadir was defined as Study Day of Nadir minus 1.
Time frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: Safety Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Hemoglobin Nadir for GSK2330811 | 30.5 Days |
| GSK2330811 450 mg | Time to Hemoglobin Nadir for GSK2330811 | 55.0 Days |
Secondary
Time to Platelet Count Nadir for GSK2330811
Blood samples were collected at indicated time points for analysis of platelet count nadir for GSK2330811. Nadir was defined as the lowest post-Baseline value of the platelet count. Time to nadir was defined as Study Day of Nadir minus 1.
Time frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 84 and 126
Population: Safety Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Platelet Count Nadir for GSK2330811 | 44.0 Days |
| GSK2330811 450 mg | Time to Platelet Count Nadir for GSK2330811 | 20.0 Days |