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The purpose of this study is to is to test increasing repeat doses of GSK249320 compared to placebo in patients with stroke.
GSK249320 is a humanised monoclonal antibody (mAb) that binds with high specificity to myelin-associated glycoprotein (MAG) and antagonises or neutralises MAG-mediated inhibition and has been shown to improve functional recovery after stroke in pre-clinical models, possibly by promoting neuroregeneration and plasticity. The present study is the first in patients with stroke. The main aim of this study is to select tolerated doses of GSK249320 that can be used in future trials to evaluate its efficacy in improving clinical function in patients recovering from stroke. This clinical trial is designed as a placebo-controlled, single-blind, multicenter study to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of escalating repeat IV doses of GSK249320. Three sequential dose escalation cohorts (1, 5 and 15 mg/kg) are planned, with 8 patients on placebo and 8 on active in cohort 1 and 4 patients on placebo and 8 on active in cohorts 2 and 3. Each patient will receive 2 repeat IV doses 9 ± 1 days apart and assessments will extend to at least 16 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PLACEBO | Placebo Comparator |
| |
| ACTIVE | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK249320 | Drug | I.V. infusion |
| |
| PLACEBO |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | Up to 112 days |
| Number of Participants With Vital Signs Changes of Potential Clinical Importance | The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (SBP) (<85 and >200 millimeter of mercury [mmHg]), diastolic blood pressure (DBP) (<45 and >110 mmHg) and heart rate (HR) (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported. | Up to 112 days |
| Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance | Single 12-lead ECGs was obtained. The standard ECG criteria of potential clinical importance were uncorrected QT interval <300 and >600 milliseconds (msec), absolute QTc interval >500 msec, increase from Baseline QTc >60 msec, RR Interval <90 and >2000 msec, PR Interval <110 and >220 msec, QRS Interval <75 and >110 msec. The number of participants with potentially clinically significant ECG abnormality were reported. | Up to 112 days |
| Number of Participants With Nerve Conduction Testing (NCT) Values |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Positive Antibodies to GSK249320 | Presence of antibodies to GSK249320 were assessed in serum samples of participants using immunoelectro-chemiluminescent assay. Number of participants with positive antibodies to GSK249320 were reported. Only visits where the true positive antibody detection was observed were reported. | Day 1, 5, 10, 30, 60, 90 and 112 |
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Inclusion Criteria:
Exclusion Criteria:
Pregnant or lactating females.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Los Angeles | California | 90095-6984 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23471268 | Background | Cramer SC, Abila B, Scott NE, Simeoni M, Enney LA; MAG111539 Study Investigators. Safety, pharmacokinetics, and pharmacodynamics of escalating repeat doses of GSK249320 in patients with stroke. Stroke. 2013 May;44(5):1337-42. doi: 10.1161/STROKEAHA.111.674366. Epub 2013 Mar 7. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 111539 | Informed Consent Form | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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A total of 42 participants were randomized and included in All subject population.
The study was conducted between 08-July-2009 and 31-January-2011 at 15 centers in 3 countries including 2 centers in Canada, 8 centers in Germany and 5 centers in the United States. Of the 15 centers, 10 centers enrolled participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Eligible participants received 0.9% Sodium chloride as an intravenous (IV) infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| FG001 | GSK249320 1 mg/kg | Eligible participants received GSK249320, 1 milligram per kilogram (mg/kg)of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| FG002 | GSK249320 5 mg/kg | Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| FG003 | GSK249320 15 mg/kg | Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Eligible participants received 0.9% Sodium chloride as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 (AE) and Serious Adverse Events (SAE) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | All Subjects population was defined as all participants who receive at least one dose of study medication. | Posted | Count of Participants | Participants | Up to 112 days |
|
AEs were collected up to Day 112
All subject population was used to report AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Eligible participants received 0.9% Sodium chloride as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ischaemic stroke | Nervous system disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
Not provided
| ID | Term |
|---|---|
| C581856 | refanezumab |
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| Drug |
Placebo |
|
NCT (electrode placement technique) of sensory and motor function was performed on the unaffected side (i.e., side that is not affected by the stroke) by appropriately qualified personnel at specified visits (Day 5 and 30 and at early withdrawal). Qualified technician performed the testing; however the same neurologist interpreted the NCT data within a single participant. Both upper and lower extremity nerves were tested and the data was recorded. Number of participants with normal and abnormal NCT data were reported. |
| Day 5 and 30 and at early withdrawal |
| Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) | Whole brain MRI scans were performed by appropriately qualified personnel at those specified visits (Day 1, 10 and 60 or at early withdrawal [if participant withdrew from study before Day 60 MRI]). Required pulse sequences of diffusion weighted imaging (DWI), T1, and T2 FLAIR was performed to measure lesion volume and to look for the presence of any new acute inflammatory lesions. The investigator or other medically qualified study team member evaluated the Day 10 and 60 scans for any new abnormalities or clinically significant worsening. Digital data for each MRI was sent to a central MRI laboratory for an over-read of the MRI scan and calculation of the lesion volume. Number of participants with change in white matter and demyelination on Day 10 compared to Day 1, Day 60 compared to Day 1 and Day 60 compared to Day 10 were reported. | Up to Day 60 |
| Number of Participants With Abnormal Clinical Chemistry Parameters | The clinical chemistry parameters analyzed were albumin, calcium, creatinine, glucose, potassium, sodium, total CO2, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. Only those parameters for which at least one abnormal value was reported are summarized. The number of participants with abnormal clinical chemistry findings at specified visit were reported. | Up to Day 112 |
| Number of Participants With Abnormal Hematological Parameters | The clinical chemistry parameters analyzed were white blood cell count, neutrophil count, hemoglobin, platelet count, lymphocytes. Only those parameters for which at least one abnormal value was reported are summarized. The number of participants with abnormal hematology findings at specified visit were reported. | Up to Day 112 |
| Mean Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC 0-inf) and Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. AUC0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. AUC(0-inf) were calculated, where data permit, as the sum of area under the concentration-time curve over the dosing interval from 0 to Day 10 ±1 day (AUC0-10d) and C10d/z, where C10d is the observed plasma concentration at day 10 and z is the terminal phase rate constant calculated after the second dose. | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) | The pharmacokinetic parameters were calculated by standard non- compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Cmax and Ct were determined directly from the raw concentration-time data. | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Tmax and tlast were determined directly from the raw concentration-time data. | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Terminal Phase Half-life (t1/2) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. The apparent t1/2 obtained as the ratio of natural log (ln)^2/ lambda-Z, where lambda-Z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Terminal Phase Rate Constant ( Lambda-Z) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Lambda-Z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Clearance of GSK249320 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. The clearance was calculated as Dose/ AUC(0-inf). | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
| Mean Change in Mean Gait Velocity | Gait velocity is an objective, quantitative, reliable, valid and sensitive measure of lower extremity motor recovery in the stroke population. Changes in gait velocity correlates with physical functioning and quality of life. Gait velocity was assessed over a level, indoor 10 meter distance. The time (in seconds) it takes the participant to travel the 10 meter distance was recorded. Participants was asked to walk at their usual or normal pace and may use their normal assistive devices. Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 5), Day 30, 60, 90, 112 |
| Mean Change in Berg Balance Scale (BBS) Total Score | BBS is a performance based measure of balance. It is reliable, valid and responsive to change in the stroke population. BBS is a staff-assessed measure that requires the participant to perform 14 activities that evaluate ability to maintain balance. The BBS typically takes 10-15minute to complete. Participants were not allowed to use assistive devices while performing the activities. Each activity was evaluated by direct observation of the participant's performance and was scored on a 5-point ordinal scale (0-4) where a score of 0 represents inability to perform the activity and a score of 4 represents independence in the activity. The minimum total score on the BBS was 0 and maximum was 56. Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 5), Day 30, 60, 90 and 112 |
| Mean Change in Total Fugl-Meyer Motor (FM) Assessment | The FM assessment is a staff-assessed, disease specific, quantitative measure of impairment that is used to assess recovery of sensorimotor function post stroke. The FM is designed to assess the domains of motor function, balance, sensation and joint function. For this study, only the motor function domain was assessed. The motor domain scale takes approximately 30 minutes to complete and evaluates both the upper and lower extremities by direct observation of the participant's performance of 50 items that measure movement, coordination, and reflex action. Each item was scored from 0-2 for a minimum total score of 0 (hemiplegia) and a maximum total score of 100 (normal motor performance). Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 5), Day 30 and 112 |
| Mean Change in Total Box and Blocks Transferred on Affected Side | The Box and Blocks test is an objective, gross manual dexterity test that is reliable and valid in individuals with upper limb impairments. Box and Blocks was a staff-assessed, participant completed test that required the participant to move small wooden blocks from one side of a partitioned box to the other. The score was determined by the number of blocks transferred within a 60 second time period. More number of blocks transferred as compared to Baseline indicated improvement. Both the impaired and normal limbs were tested, starting with the normal limb. The number of blocks transferred were recorded. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 1), Day 30, 60, 90 and 112 |
| Mean Change in Grip Strength on Affected Side | Grip strength is an objective measure of arm motor recovery in stroke participants and correlate with functional status and predict recovery. Grip strength was evaluated by a hand grip dynamometer. Three replicate trials was collected for both the impaired and normal hand, starting with the normal hand. Each trial was separated by a resting period of approximately 15-30 seconds. Participants was instructed to squeeze as hard as possible while using a standardized position of grip and the resulting dynamometer reading (in kg) was recorded. The grip strength measures was conducted within approximately 5 minutes. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 1), Day 30, 60, 90 and 112 |
| Number of Participants With Modified Rankin Scale (mRS) | The mRS was a 6 point scale that measured participant handicap by evaluating limitations in activity and changes in lifestyle. The mRS was staff-assessed and scored from 0=no symptoms at all, 1=no significant disability, 2=slight disability, 3=moderate disability, 4=moderate severe disability, 5=severe disability (severe disability, bedridden, incontinent and requiring constant nursing care and attention). The structured interview was used to administer the mRS. The mRS took approximately 15 minutes to complete when using the structured interview. Number of participants with mRS were reported as per the category of the score. | Day 30 and 90 |
| Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) | The NIHSS is a staff-assessed, 15 item, standardized, disease-specific, deficit scale which measures neurological impairment and is used to quantify participant status by measuring the severity of the stroke. The total NIHSS score ranged from 0 (No impairment) to 42 (severe impairment). Approximately 15 minutes were needed to complete the NIHSS. The NIHSS will be collected as part of the eligibility requirements to exclude participants who have a deficit that is either too mild or too severe. Only NIHSS certified study personnel recorded the NIHSS. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 1), Day 10, 30 and 90 |
| Mean Barthel Total Score | The Barthel was a staff-assessed, 10 item activities of daily living index that evaluated feeding, grooming, dressing, excretion (bowels, bladder and toilet skills), bathing, and mobility (transfers, walking, stairs). The total Barthel score ranged from either 0-20 or 0-100 depending on which scoring algorithm was used where 0= unable or dependent and 20 or 100= independent to perform daily activities. For this study, the 100 point scoring algorithm was used. The Barthel takes approximately 5-10 minutes to complete with the participant. | Day 30 and 90 |
| Mean Total Montreal Cognitive Assessment (MoCA) Score | MoCA was an examiner-administered, screening instrument with good validity, reliability, sensitivity and specificity for mild cognitive dysfunction. The MoCA had been studied in stroke participants and was recommended as a tool to monitor and measure cognitive changes post stroke as part of the 2006 National Institute of Neurological Disorders and Stroke - Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards. The MoCA assesses eight cognitive domains of visuospatial skills, executive function, language, attention, concentration, working memory, memory, and orientation. Participants were asked to complete 14 activities which the examiner scored according to the standardized scoring instructions. While there was no set time limit imposed on a participant. The total MoCA score ranges from 0-30, where 0= worsening and 30 reflects normal cognitive function. | Day 5 and 90 |
| Mean Geriatric Depression Scale (GDS) | The short form GDS is a measure of depression developed specifically for use in elderly population and is sensitive and valid in the stroke population. The GDS was a participant-completed, 15 item questionnaire where each question referenced how the participant felt over the past week. Each question was answered with either a 'yes' or 'no' response. Of the 15 questions, 10 of them indicate depression when answered 'yes' (questions 2-4, 6, 8-10, 12, 14-15) and 5 indicate depression when answered 'no' (questions 1, 5, 7, 11, 13). Each question received a score of 1 point when the response was indicative of depression. Total score ranged from 0 to 15. the total score ranged from 0-15, where 0 implies no symptoms and higher score implies more severity of symptoms. | Day 5 and 90 |
| Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level | TMS is an electrophysiological technique that was used to measure neurologic changes associated with recovery from stroke via alterations in the excitability of the motor system. Motor threshold measures reflect global excitability of the corticospinal pathway, including large pyramidal cells, excitatory/inhibitory interneurons, and spinal motorneurons. Motor threshold was recorded as the lowest stimulus intensity (in percent) eliciting motor evoked potentials (MEPs). Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post -randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | Baseline (Day 1), Day 30 and 112 |
| Serum Levels of the S100β Protein | The serum sample for S100β collected on Day 1 (predose, 1, 6, 12 and 24 hour) and Day 5 and was analyzed for levels. Serum levels of S100β protein were recorded as log transformed values therefore the negative values are reported. | Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5 |
| Orange |
| California |
| 92868-4280 |
| United States |
| GSK Investigational Site | Fort Collins | Colorado | 80524 | United States |
| GSK Investigational Site | Detroit | Michigan | 48201 | United States |
| GSK Investigational Site | Portland | Oregon | 97239 | United States |
| GSK Investigational Site | Toronto | Ontario | M4N 3M5 | Canada |
| GSK Investigational Site | Montreal | Quebec | H3T 1E2 | Canada |
| GSK Investigational Site | Ulm | Baden-Wurttemberg | 89081 | Germany |
| GSK Investigational Site | Wiesbaden | Hesse | 65199 | Germany |
| GSK Investigational Site | Celle | Lower Saxony | 29223 | Germany |
| GSK Investigational Site | Hanover | Lower Saxony | 30625 | Germany |
| GSK Investigational Site | Cologne | North Rhine-Westphalia | 50937 | Germany |
| GSK Investigational Site | Essen | North Rhine-Westphalia | 45122 | Germany |
| GSK Investigational Site | Mainz | Rhineland-Palatinate | 55131 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04103 | Germany |
For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 111539 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| Withdrawal by Subject |
|
| BG001 |
| GSK249320 1 mg/kg |
Eligible participants received GSK249320, 1 mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| BG002 | GSK249320 5 mg/kg | Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| BG003 | GSK249320 15 mg/kg | Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks |
| BG004 | Total | Total of all reporting groups |
| Year |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Placebo |
Eligible participants received 0.9% Sodium chloride as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| OG001 | GSK249320 1 mg/kg | Eligible participants received GSK249320, 1 mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| OG002 | GSK249320 5 mg/kg | Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. |
| OG003 | GSK249320 15 mg/kg | Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks |
|
|
| Primary | Number of Participants With Vital Signs Changes of Potential Clinical Importance | The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (SBP) (<85 and >200 millimeter of mercury [mmHg]), diastolic blood pressure (DBP) (<45 and >110 mmHg) and heart rate (HR) (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Up to 112 days |
|
|
|
| Primary | Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance | Single 12-lead ECGs was obtained. The standard ECG criteria of potential clinical importance were uncorrected QT interval <300 and >600 milliseconds (msec), absolute QTc interval >500 msec, increase from Baseline QTc >60 msec, RR Interval <90 and >2000 msec, PR Interval <110 and >220 msec, QRS Interval <75 and >110 msec. The number of participants with potentially clinically significant ECG abnormality were reported. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Up to 112 days |
|
|
|
| Primary | Number of Participants With Nerve Conduction Testing (NCT) Values | NCT (electrode placement technique) of sensory and motor function was performed on the unaffected side (i.e., side that is not affected by the stroke) by appropriately qualified personnel at specified visits (Day 5 and 30 and at early withdrawal). Qualified technician performed the testing; however the same neurologist interpreted the NCT data within a single participant. Both upper and lower extremity nerves were tested and the data was recorded. Number of participants with normal and abnormal NCT data were reported. | All Subject population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Day 5 and 30 and at early withdrawal |
|
|
|
| Primary | Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) | Whole brain MRI scans were performed by appropriately qualified personnel at those specified visits (Day 1, 10 and 60 or at early withdrawal [if participant withdrew from study before Day 60 MRI]). Required pulse sequences of diffusion weighted imaging (DWI), T1, and T2 FLAIR was performed to measure lesion volume and to look for the presence of any new acute inflammatory lesions. The investigator or other medically qualified study team member evaluated the Day 10 and 60 scans for any new abnormalities or clinically significant worsening. Digital data for each MRI was sent to a central MRI laboratory for an over-read of the MRI scan and calculation of the lesion volume. Number of participants with change in white matter and demyelination on Day 10 compared to Day 1, Day 60 compared to Day 1 and Day 60 compared to Day 10 were reported. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Up to Day 60 |
|
|
|
| Primary | Number of Participants With Abnormal Clinical Chemistry Parameters | The clinical chemistry parameters analyzed were albumin, calcium, creatinine, glucose, potassium, sodium, total CO2, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. Only those parameters for which at least one abnormal value was reported are summarized. The number of participants with abnormal clinical chemistry findings at specified visit were reported. | All Subjects population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Posted | Count of Participants | Participants | Up to Day 112 |
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| Primary | Number of Participants With Abnormal Hematological Parameters | The clinical chemistry parameters analyzed were white blood cell count, neutrophil count, hemoglobin, platelet count, lymphocytes. Only those parameters for which at least one abnormal value was reported are summarized. The number of participants with abnormal hematology findings at specified visit were reported. | All Subjects population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Posted | Count of Participants | Participants | Up to Day 112 |
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| Secondary | Number of Participants With Positive Antibodies to GSK249320 | Presence of antibodies to GSK249320 were assessed in serum samples of participants using immunoelectro-chemiluminescent assay. Number of participants with positive antibodies to GSK249320 were reported. Only visits where the true positive antibody detection was observed were reported. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Day 1, 5, 10, 30, 60, 90 and 112 |
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| Secondary | Mean Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC 0-inf) and Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. AUC0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. AUC(0-inf) were calculated, where data permit, as the sum of area under the concentration-time curve over the dosing interval from 0 to Day 10 ±1 day (AUC0-10d) and C10d/z, where C10d is the observed plasma concentration at day 10 and z is the terminal phase rate constant calculated after the second dose. | Pharmacokinetic population comprised of participants from the 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | Hour*mg/millilitre (mL) | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) | The pharmacokinetic parameters were calculated by standard non- compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Cmax and Ct were determined directly from the raw concentration-time data. | Pharmacokinetic population. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | microgram (ug) per mL | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Tmax and tlast were determined directly from the raw concentration-time data. | Pharmacokinetics population. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | hour | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Terminal Phase Half-life (t1/2) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. The apparent t1/2 obtained as the ratio of natural log (ln)^2/ lambda-Z, where lambda-Z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. | Pharmacokinetics population. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | Day | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Terminal Phase Rate Constant ( Lambda-Z) | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. Lambda-Z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. | Pharmacokinetics population. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | 1/ hour | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Clearance of GSK249320 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis using Win Nonlin Pro 4.1. All calculations of non-compartmental parameters were based on actual sampling times. The clearance was calculated as Dose/ AUC(0-inf). | Pharmacokinetics population. Only those participants with data available for analysis were analyzed. | Posted | Mean | Standard Deviation | mL/hour/killogram (kg) | Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour) |
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| Secondary | Mean Change in Mean Gait Velocity | Gait velocity is an objective, quantitative, reliable, valid and sensitive measure of lower extremity motor recovery in the stroke population. Changes in gait velocity correlates with physical functioning and quality of life. Gait velocity was assessed over a level, indoor 10 meter distance. The time (in seconds) it takes the participant to travel the 10 meter distance was recorded. Participants was asked to walk at their usual or normal pace and may use their normal assistive devices. Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Meters/second | Baseline (Day 5), Day 30, 60, 90, 112 |
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| Secondary | Mean Change in Berg Balance Scale (BBS) Total Score | BBS is a performance based measure of balance. It is reliable, valid and responsive to change in the stroke population. BBS is a staff-assessed measure that requires the participant to perform 14 activities that evaluate ability to maintain balance. The BBS typically takes 10-15minute to complete. Participants were not allowed to use assistive devices while performing the activities. Each activity was evaluated by direct observation of the participant's performance and was scored on a 5-point ordinal scale (0-4) where a score of 0 represents inability to perform the activity and a score of 4 represents independence in the activity. The minimum total score on the BBS was 0 and maximum was 56. Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on Scale | Baseline (Day 5), Day 30, 60, 90 and 112 |
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| Secondary | Mean Change in Total Fugl-Meyer Motor (FM) Assessment | The FM assessment is a staff-assessed, disease specific, quantitative measure of impairment that is used to assess recovery of sensorimotor function post stroke. The FM is designed to assess the domains of motor function, balance, sensation and joint function. For this study, only the motor function domain was assessed. The motor domain scale takes approximately 30 minutes to complete and evaluates both the upper and lower extremities by direct observation of the participant's performance of 50 items that measure movement, coordination, and reflex action. Each item was scored from 0-2 for a minimum total score of 0 (hemiplegia) and a maximum total score of 100 (normal motor performance). Baseline assessments were recorded at Day 5 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on Scale | Baseline (Day 5), Day 30 and 112 |
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| Secondary | Mean Change in Total Box and Blocks Transferred on Affected Side | The Box and Blocks test is an objective, gross manual dexterity test that is reliable and valid in individuals with upper limb impairments. Box and Blocks was a staff-assessed, participant completed test that required the participant to move small wooden blocks from one side of a partitioned box to the other. The score was determined by the number of blocks transferred within a 60 second time period. More number of blocks transferred as compared to Baseline indicated improvement. Both the impaired and normal limbs were tested, starting with the normal limb. The number of blocks transferred were recorded. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Blocks | Baseline (Day 1), Day 30, 60, 90 and 112 |
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| Secondary | Mean Change in Grip Strength on Affected Side | Grip strength is an objective measure of arm motor recovery in stroke participants and correlate with functional status and predict recovery. Grip strength was evaluated by a hand grip dynamometer. Three replicate trials was collected for both the impaired and normal hand, starting with the normal hand. Each trial was separated by a resting period of approximately 15-30 seconds. Participants was instructed to squeeze as hard as possible while using a standardized position of grip and the resulting dynamometer reading (in kg) was recorded. The grip strength measures was conducted within approximately 5 minutes. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Kg | Baseline (Day 1), Day 30, 60, 90 and 112 |
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| Secondary | Number of Participants With Modified Rankin Scale (mRS) | The mRS was a 6 point scale that measured participant handicap by evaluating limitations in activity and changes in lifestyle. The mRS was staff-assessed and scored from 0=no symptoms at all, 1=no significant disability, 2=slight disability, 3=moderate disability, 4=moderate severe disability, 5=severe disability (severe disability, bedridden, incontinent and requiring constant nursing care and attention). The structured interview was used to administer the mRS. The mRS took approximately 15 minutes to complete when using the structured interview. Number of participants with mRS were reported as per the category of the score. | All subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Count of Participants | Participants | Day 30 and 90 |
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| Secondary | Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) | The NIHSS is a staff-assessed, 15 item, standardized, disease-specific, deficit scale which measures neurological impairment and is used to quantify participant status by measuring the severity of the stroke. The total NIHSS score ranged from 0 (No impairment) to 42 (severe impairment). Approximately 15 minutes were needed to complete the NIHSS. The NIHSS will be collected as part of the eligibility requirements to exclude participants who have a deficit that is either too mild or too severe. Only NIHSS certified study personnel recorded the NIHSS. Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Baseline (Day 1), Day 10, 30 and 90 |
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| Secondary | Mean Barthel Total Score | The Barthel was a staff-assessed, 10 item activities of daily living index that evaluated feeding, grooming, dressing, excretion (bowels, bladder and toilet skills), bathing, and mobility (transfers, walking, stairs). The total Barthel score ranged from either 0-20 or 0-100 depending on which scoring algorithm was used where 0= unable or dependent and 20 or 100= independent to perform daily activities. For this study, the 100 point scoring algorithm was used. The Barthel takes approximately 5-10 minutes to complete with the participant. | All subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Day 30 and 90 |
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| Secondary | Mean Total Montreal Cognitive Assessment (MoCA) Score | MoCA was an examiner-administered, screening instrument with good validity, reliability, sensitivity and specificity for mild cognitive dysfunction. The MoCA had been studied in stroke participants and was recommended as a tool to monitor and measure cognitive changes post stroke as part of the 2006 National Institute of Neurological Disorders and Stroke - Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards. The MoCA assesses eight cognitive domains of visuospatial skills, executive function, language, attention, concentration, working memory, memory, and orientation. Participants were asked to complete 14 activities which the examiner scored according to the standardized scoring instructions. While there was no set time limit imposed on a participant. The total MoCA score ranges from 0-30, where 0= worsening and 30 reflects normal cognitive function. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Day 5 and 90 |
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| Secondary | Mean Geriatric Depression Scale (GDS) | The short form GDS is a measure of depression developed specifically for use in elderly population and is sensitive and valid in the stroke population. The GDS was a participant-completed, 15 item questionnaire where each question referenced how the participant felt over the past week. Each question was answered with either a 'yes' or 'no' response. Of the 15 questions, 10 of them indicate depression when answered 'yes' (questions 2-4, 6, 8-10, 12, 14-15) and 5 indicate depression when answered 'no' (questions 1, 5, 7, 11, 13). Each question received a score of 1 point when the response was indicative of depression. Total score ranged from 0 to 15. the total score ranged from 0-15, where 0 implies no symptoms and higher score implies more severity of symptoms. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Day 5 and 90 |
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| Secondary | Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level | TMS is an electrophysiological technique that was used to measure neurologic changes associated with recovery from stroke via alterations in the excitability of the motor system. Motor threshold measures reflect global excitability of the corticospinal pathway, including large pyramidal cells, excitatory/inhibitory interneurons, and spinal motorneurons. Motor threshold was recorded as the lowest stimulus intensity (in percent) eliciting motor evoked potentials (MEPs). Baseline assessments were recorded at Day 1 of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post -randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. | All subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Percent change in stimulation | Baseline (Day 1), Day 30 and 112 |
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| Secondary | Serum Levels of the S100β Protein | The serum sample for S100β collected on Day 1 (predose, 1, 6, 12 and 24 hour) and Day 5 and was analyzed for levels. Serum levels of S100β protein were recorded as log transformed values therefore the negative values are reported. | All Subjects population. Only those participants with data available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | log (ug per liter) | Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5 |
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| 0 |
| 17 |
| 3 |
| 17 |
| 9 |
| 17 |
| EG001 | GSK249320 1 mg/kg | Eligible participants received GSK249320, 1 mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. | 0 | 8 | 1 | 8 | 6 | 8 |
| EG002 | GSK249320 5 mg/kg | Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks. | 0 | 9 | 3 | 9 | 7 | 9 |
| EG003 | GSK249320 15 mg/kg | Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks | 0 | 8 | 3 | 8 | 5 | 8 |
| Cerebral infarction | Nervous system disorders | MedDRA | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
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| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA | Systematic Assessment |
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| Helicobacter infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Peridiverticulitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Post procedural complication | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Peripheral arterial occlusive disease | Vascular disorders | MedDRA | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Glucose tolerance impaired | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Bacterial infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Clostridial infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Fungal skin infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Gastrointestinal infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Restlessness | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
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| Atrial flutter | Cardiac disorders | MedDRA | Systematic Assessment |
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| Atrioventricular block | Cardiac disorders | MedDRA | Systematic Assessment |
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| Atrioventricular block complete | Cardiac disorders | MedDRA | Systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
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| Sinus arrhythmia | Cardiac disorders | MedDRA | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Apnoeic attack | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Throat tightness | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Blister | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Blood albumin decreased | Investigations | MedDRA | Systematic Assessment |
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| Protein total abnormal | Investigations | MedDRA | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
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| Conjunctivitis | Eye disorders | MedDRA | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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| SBP, Visit 1, Day 1, 1 hour, High |
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| SBP, Visit 1, Day 1, 1 hour, Low |
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| SBP, Visit 1, Day 1, 2 hour, High |
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| SBP, Visit 1, Day 1, 4 hour, High |
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| SBP, Visit 1, Day 1, 8 hour, High |
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| SBP, Visit 1, Day 1, 12 hour, High |
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| SBP, Visit 1, Day 1, 12 hour, Low |
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| SBP, Visit 1, Day 1, 24 hour, High |
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| SBP, Visit 6, Day 90, Low |
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| SBP, Visit 7, Day 112, Low |
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| DBP, Visit 1, Day 1, 15 minute, Low |
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| DBP, Visit 1, Day 1, 1 hour, High |
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| DBP, Visit 1, Day 1, 2 hour, High |
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| DBP, Visit 1, Day 1, 2 hour, Low |
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| DBP, Visit 1, Day 1, 4 hour, High |
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| DBP, Visit 1, Day 1, 12 hour, High |
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| DBP, Visit 2, Day 5, High |
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| DBP, Visit 3, Day 10, 30 minute, High |
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| HR, Visit 1, Day 1, 0 hour, High |
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| HR, Visit 1, Day 1, 15 minute, High |
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| HR, Visit 1, Day 1, 30 minute, High |
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| HR, Visit 1, Day 1, 45 minute, High |
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| HR, Visit 1, Day 1, 1 hour, High |
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| HR, Visit 1, Day 1, 2 hour, High |
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| HR, Visit 1, Day 1, 12 hour, High |
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| HR, Visit 1, Day 1, 24 hour, High |
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| HR, Visit 2, Day 5, High |
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| HR, Visit 3, Day 10, 0 hour, High |
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| HR, Visit 3, Day 10, 15 minute, High |
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| HR, Visit 3, Day 10, 30 minute, High |
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| HR, Visit 3, Day 10, 45 minute, High |
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| HR, Visit 3, Day 10, 1 hour, High |
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| HR, Visit 3, Day 10, 3 hour, High |
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| HR, Visit 4, Day 30, High |
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| Visit 1, Day 1, 24 hour |
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| Visit 2, Day 5 |
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| Visit 3, Day 10, Predose |
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| Visit 3, Day 10, 3 hour |
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| Visit 4, Day 30 |
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| Visit 5, Day 60 |
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| Visit 6, Day 90 |
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| Visit 7, Day 112 |
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| Motor, Visit 2, Day 5, Abnormal, secondary to |
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| Motor, Visit 4, Day 30, Normal |
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| Motor, Visit 4, Day 30, Abnormal, secondary to |
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| Motor, Early Withdrawal, Abnormal, secondary to |
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| Sensory, Visit 2, Day 5, Normal |
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| Sensory, Visit 2, Day 5, Abnormal, secondary to |
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| Sensory, Not done |
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| Sensory, Visit 4, Day 30, Normal |
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| Sensory, Visit 4, Day 30, Abnormal, secondary to |
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| Sensory, Early Withdrawal, Normal, |
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| Sensory, Early Withdrawal, Abnormal, secondary to |
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| White matter change, Day 60 compared to Day 1 |
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| White matter change, Day 60 compared to Day 10 |
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| Demyelination, Day 10 compared to Day 1, Yes |
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| Demyelination, Day 10 compared to Day 1, No |
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| Demyelination, Day 60 compared to Day 1, No |
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| Demyelination, Day 60 compared to Day 10, No |
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| Demyelination, During Study, Yes |
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| Demyelination, During Study, No |
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| Albumin, Visit 2 , Day 5, Low |
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| Albumin, Visit 3 , Day 10, Pre-dose, Low |
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| Albumin, Visit 3 , Day 10, 3 hour, Low |
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| Albumin, Visit 5 , Day 60, Low |
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| ALT, visit 4, day 30, high |
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| ALT, Visit 6, Day 90, High |
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| ALT, Visit 7, Day 112, High |
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| AST, Visit 4, Day 30, High |
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| AST, Visit 6, Day 90, High |
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| AST, Visit 7, Day 112, High |
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| Calcium, Visit1 , Day 1, Pre-dose, Low |
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| Calcium, Visit1 , Day 1, 24 hour, Low |
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| CO2, Visit 1, Day 1, Pre-dose, Low |
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| CO2, Visit 1, Day 1, 24 hour, Low |
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| CO2, Visit 2, Day 5, Low |
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| CO2, Visit 3, Day 10, Pre-dose, Low |
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| CO2, Visit 3, Day 10, 3H, Low |
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| CO2, Visit 4, Day 30, Low |
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| CO2, Visit 5, Day 60, Low |
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| CO2, Visit 6, Day 90, Low |
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| CO2, Visit 7, Day 112, Low |
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| CO2, Early Withdrawal, Low |
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| Creatinine, Visit1 , Day 1, Pre-dose, High |
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| Creatinine, Visit 2 , Day 5, High |
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| Creatinine, Visit 3, Day 10, Pre-dose, High |
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| Creatinine, Visit 3, Day 10, 3 hour, High |
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| Creatinine, Visit 4, Day 30, High |
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| Creatinine, Visit 5, Day 60, High |
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| Creatinine, Visit 6 Day 90, High |
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| Glucose, Visit 1, Day 1, Pre-dose, High |
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| Glucose, Visit 1, Day 1, Pre-dose, Low |
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| Glucose, Visit 1, Day 1, 24 hour, High |
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| Glucose, Visit 1, Day 1, 24 hour, Low |
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| Glucose, Visit 2, Day 5, High |
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| Glucose, Visit 3, Day 10, Pre-dose, High |
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| Glucose, Visit 3, Day 10, 3 hour, High |
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| Glucose, Visit 4, Day 30, High |
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| Glucose, Visit 5, Day 60, High |
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| Glucose, Visit 6, Day 90, High |
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| Glucose, Visit 7, Day 112, High |
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| Potassium, Visit 1, Day 1, 24 hour, High |
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| Potassium, Visit 3, Day 10, Pre-dose, High |
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| Potassium, Visit 5, Day 60, High |
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| Sodium, Visit 2, Day 5, Low |
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|
| Sodium, Visit 3, Day 10, 3 hour, Low |
|
|
| Sodium, Visit 4, Day 30, Low |
|
|
|
| Lymphocytes, Visit 1, Day 1, 24 hour, Low |
|
|
| Lymphocytes, Visit 2, Day 5, Low |
|
|
| Lymphocytes, Visit 6, Day 90, Low |
|
|
| Lymphocytes, Visit 7, Day 112, Low |
|
|
| Lymphocytes, Early withdrawal, Low |
|
|
| Total Neutrophils, Visit 5, Day 60, Low |
|
|
| Total Neutrophils, Visit 6, Day 90, Low |
|
|
| Platelet count, Visit 4, Day 30, High |
|
|
| Platelet count, Visit 5, Day 60, High |
|
|
|
| Visit 3 Day 10 True positive |
|
|
| Visit 4 Day 30 True positive |
|
|
| Visit 5 Day 60 True positive |
|
|
| AUC(0-t), Dose 1 |
|
|
| AUC(0-t), Dose 2 |
|
|
| Cmax, Dose 2 |
|
|
| Ct, Dose 1 |
|
|
| Ct, Dose 2 |
|
|
| tmax, Dose 2 |
|
|
| tlast, Dose 1 |
|
|
| tlast, Dose 2 |
|
|
| lambda-z, Dose 2 |
|
|
|
| Visit 5 Day 60 |
|
|
| Visit 6 Day 90 |
|
|
| Visit 7 Day 112 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measure Analysis |
| Mean Difference (Net) |
| 0.69 |
| Standard Error of the Mean |
| 0.214 |
| 2-Sided |
| 95 |
| 0.25 |
| 1.13 |
Mean difference = GSK249320 5 mg/kg - Placebo |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.30 | Standard Error of the Mean | 0.246 | 2-Sided | 95 | -0.20 | 0.80 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 5 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.35 | Standard Error of the Mean | 0.292 | 2-Sided | 95 | -0.24 | 0.95 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 5 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.52 | Standard Error of the Mean | 0.279 | 2-Sided | 95 | -0.05 | 1.09 | Mean difference= GSK249320 5 mg/kg- Placebo | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 5 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.04 | Standard Error of the Mean | 0.319 | 2-Sided | 95 | -0.61 | 0.69 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.63 | Standard Error of the Mean | 0.235 | 2-Sided | 95 | 0.15 | 1.11 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.40 | Standard Error of the Mean | 0.225 | 2-Sided | 95 | -0.06 | 0.86 | Mean difference= GSK249320 5 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.24 | Standard Error of the Mean | 0.259 | 2-Sided | 95 | -0.29 | 0.77 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 7 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.61 | Standard Error of the Mean | 0.251 | 2-Sided | 95 | 0.10 | 1.12 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.59 | Standard Error of the Mean | 0.242 | 2-Sided | 95 | 0.09 | 1.08 | Mean difference= GSK249320 5 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measure Analysis | Mean Difference (Net) | 0.17 | Standard Error of the Mean | 0.277 | 2-Sided | 95 | -0.39 | 0.73 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
|
| Visit 5 Day 60 |
|
|
| Visit 6 Day 90 |
|
|
| Visit 7 Day 112 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| 8.47 |
| Standard Error of the Mean |
| 4.801 |
| 2-Sided |
| 95 |
| -1.32 |
| 18.26 |
Mean difference= GSK249320 5 mg/kg - Placebo |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Median Difference (Final Values) | 0.09 | Standard Error of the Mean | 5.470 | 2-Sided | 95 | -11.1 | 11.24 | Mean difference= GSK249320 GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 11.58 | Standard Error of the Mean | 5.631 | 2-Sided | 95 | 0.01 | 23.15 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 8.77 | Standard Error of the Mean | 5.411 | 2-Sided | 95 | -2.35 | 19.89 | Mean difference= GSK249320 5 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Final Values) | 0.49 | Standard Error of the Mean | 6.195 | 2-Sided | 95 | -12.2 | 13.21 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 9.66 | Standard Error of the Mean | 5.351 | 2-Sided | 95 | -1.34 | 20.66 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 7.45 | Standard Error of the Mean | 5.198 | 2-Sided | 95 | -3.22 | 18.13 | Mean difference= GSK249320 5 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -10.63 | Standard Error of the Mean | 5.959 | 2-Sided | 95 | -22.9 | 1.60 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 9.59 | Standard Error of the Mean | 6.134 | 2-Sided | 95 | -3.07 | 22.24 | Mean difference= GSK249320 1 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 5.89 | Standard Error of the Mean | 5.948 | 2-Sided | 95 | -6.37 | 18.15 | Mean difference= GSK249320 5 mg/kg - Placebo | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -3.11 | Standard Error of the Mean | 6.768 | 2-Sided | 95 | -17.1 | 10.84 | Mean difference= GSK249320 15 mg/kg - Placebo | Superiority or Other |
|
| Total Score, Visit 7 Day 112 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measures Analysis |
| Median Difference (Net) |
| 9.86 |
| Standard Error of the Mean |
| 6.852 |
| 2-Sided |
| 95 |
| -4.08 |
| 23.80 |
Mean difference= GSK249320 5 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -5.40 | Standard Error of the Mean | 7.376 | 2-Sided | 95 | -20.41 | 9.60 | Mean difference= GSK249320 15 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -2.40 | Standard Error of the Mean | 10.040 | 2-Sided | 95 | -22.87 | 18.07 | Mean difference= GSK249320 1 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 5.03 | Standard Error of the Mean | 10.310 | 2-Sided | 95 | -15.95 | 26.00 | Mean difference= GSK249320 5 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -10.07 | Standard Error of the Mean | 10.916 | 2-Sided | 95 | -32.29 | 12.15 | Mean difference= GSK249320 15 mg/kg - Placebo Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
|
| Visit 5 Day 60 |
|
|
| Visit 6 Day 90 |
|
|
| Visit 7 Day 112 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| 2.75 |
| Standard Error of the Mean |
| 5.157 |
| 2-Sided |
| 95 |
| -7.75 |
| 13.26 |
Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 4.85 | Standard Error of the Mean | 5.409 | 2-Sided | 95 | -6.17 | 15.88 | Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.20 | Standard Error of the Mean | 6.504 | 2-Sided | 95 | -12.1 | 14.45 | Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 2.05 | Standard Error of the Mean | 6.426 | 2-Sided | 95 | -11.0 | 15.12 | Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -2.22 | Standard Error of the Mean | 6.820 | 2-Sided | 95 | -16.1 | 11.68 | Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | 0.63 | Standard Error of the Mean | 6.664 | 2-Sided | 95 | -12.9 | 14.18 | Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.03 | Standard Error of the Mean | 6.595 | 95 | -12.4 | 14.43 | Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -0.95 | Standard Error of the Mean | 7.020 | 2-Sided | 95 | -15.2 | 13.32 | Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 2.25 | Standard Error of the Mean | 6.953 | 2-Sided | 95 | -11.9 | 16.40 | Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 3.52 | Standard Error of the Mean | 6.909 | 2-Sided | 95 | -10.5 | 17.55 | Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.50 | Standard Error of the Mean | 7.328 | 2-Sided | 95 | -15.4 | 14.39 | Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
|
| Visit 5 Day 60 |
|
|
| Visit 6 Day 90 |
|
|
| Visit 7 Day 112 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| -0.30 |
| Standard Error of the Mean |
| 3.550 |
| 2-Sided |
| 95 |
| -7.56 |
| 6.96 |
Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 4.56 | Standard Error of the Mean | 3.534 | 2-Sided | 95 | -2.67 | 11.78 | Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 2.05 | Standard Error of the Mean | 3.841 | 2-Sided | 95 | -5.78 | 9.89 | Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -2.35 | Standard Error of the Mean | 3.958 | 2-Sided | 95 | -10.4 | 5.72 | Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 5 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.44 | Standard Error of the Mean | 3.978 | 2-Sided | 95 | -6.68 | 9.55 | Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 3.46 | Standard Error of the Mean | 4.109 | 2-Sided | 95 | -4.94 | 11.85 | Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.49 | Standard Error of the Mean | 4.235 | 2-Sided | 95 | -8.15 | 9.12 | Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | 0.77 | Standard Error of the Mean | 4.280 | 2-Sided | 95 | -7.97 | 9.50 | Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 3.04 | Standard Error of the Mean | 4.205 | 2-Sided | 95 | -5.53 | 11.61 | Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -2.58 | Standard Error of the Mean | 4.376 | 2-Sided | 95 | -11.5 | 6.32 | Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 7 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 3.73 | Standard Error of the Mean | 4.396 | 2-Sided | 95 | -5.22 | 12.69 | Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline | Superiority or Other |
|
| Visit 6 Day 90 |
|
|
| 0.5647 |
| Superiority or Other |
|
| Visit 4 Day 30 |
|
|
| Visit 6 Day 90 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 3 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| -0.19 |
| Standard Error of the Mean |
| 0.861 |
| 2-Sided |
| 95 |
| -1.95 |
| 1.57 |
Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 3 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -2.92 | Standard Error of the Mean | 0.933 | 2-Sided | 95 | -4.83 | -1.02 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.70 | Standard Error of the Mean | 0.868 | 2-Sided | 95 | -2.47 | 1.08 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -0.27 | Standard Error of the Mean | 0.834 | 2-Sided | 95 | -1.98 | 1.44 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -0.92 | Standard Error of the Mean | 0.904 | 2-Sided | 95 | -2.77 | 0.92 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -1.03 | Standard Error of the Mean | 1.278 | 2-Sided | 95 | -3.64 | 1.57 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.37 | Standard Error of the Mean | 1.278 | 2-Sided | 95 | -2.97 | 2.24 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -0.37 | Standard Error of the Mean | 2.21 | 2-Sided | 95 | -0.66 | 1.408 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline | Superiority or Other |
|
| Visit 6 Day 90 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 4 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| 20.99 |
| Standard Error of the Mean |
| 12.131 |
| 2-Sided |
| 95 |
| -3.66 |
| 45.64 |
Mean difference= GSK249320 5 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 4 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 11.79 | Standard Error of the Mean | 13.143 | 2-Sided | 95 | -14.9 | 38.50 | Mean difference= GSK249320 15 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit | Superiority or Other |
| Placebo Vs GSK249320 1 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 15.71 | Standard Error of the Mean | 9.021 | 2-Sided | 95 | -2.63 | 34.06 | Mean difference= GSK249320 1 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit | Superiority or Other |
| Placebo Vs GSK249320 5 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 11.56 | Standard Error of the Mean | 8.835 | 2-Sided | 95 | -6.38 | 29.50 | Mean difference= GSK249320 5 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit | Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -7.49 | Standard Error of the Mean | 9.641 | 2-Sided | 95 | -27.1 | 12.08 | Mean difference= GSK249320 15 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit | Superiority or Other |
|
| Visit 6 Day 90 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 6 |
| ANCOVA |
| Median Difference (Net) |
| -0.17 |
| Standard Error of the Mean |
| 1.856 |
| 2-Sided |
| 95 |
| -3.96 |
| 3.62 |
Mean difference= GSK249320 5 mg/kg - Placebo Day 90 MoCA = Treatment + Day 5 MoCA |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | ANCOVA | Mean Difference (Net) | -1.15 | Standard Error of the Mean | 2.037 | 2-Sided | 95 | -5.31 | 3.01 | Mean difference= GSK249320 15 mg/kg - Placebo Day 90 MoCA = Treatment + Day 5 MoCA | Superiority or Other |
|
| Visit 6 Day 90 |
|
|
Placebo Vs GSK249320 5 mg/kg, Visit 6 |
| ANCOVA |
| Mean Difference (Net) |
| 1.55 |
| Standard Error of the Mean |
| 1.347 |
| 2-Sided |
| 95 |
| -1.20 |
| 4.30 |
Mean difference= GSK249320 5 mg/kg - Placebo Day 90 GDS Score= Treatment + Day 5 GDS Score |
| Superiority or Other |
| Placebo Vs GSK249320 15 mg/kg, Visit 6 | ANCOVA | Mean Difference (Net) | -0.06 | Standard Error of the Mean | 1.486 | 2-Sided | 95 | -3.09 | 2.98 | Mean difference= GSK249320 15 mg/kg - Placebo. Day 90 GDS Score= Treatment+Day 5 GDS Score | Superiority or Other |
|
| Stimulation Level 100%, Visit 7 Day 112 |
|
|
| Stimulation Level 110%, Visit 4 Day 30 |
|
|
| Stimulation Level 110%, Visit 7 Day 112 |
|
|
| Stimulation Level 120%, Visit 4 Day 30 |
|
|
| Stimulation Level 120%, Visit 7 Day 112 |
|
|
| Stimulation Level 130%, Visit 4 Day 30 |
|
|
| Stimulation Level 130%, Visit 7 Day 112 |
|
|
| Stimulation Level 140%, Visit 4 Day 30 |
|
|
| Stimulation Level 140%, Visit 7 Day 112 |
|
|
Stimulation Level 100%, Visit 4 Day 30 |
| Mixed Model Repeated Measures Analysis |
| Mean Difference (Net) |
| -0.310 |
| Standard Error of the Mean |
| 0.2637 |
| 2-Sided |
| 95 |
| -0.862 |
| 0.241 |
Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline |
| Superiority or Other |
| Stimulation Level 100%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | -0.303 | Standard Error of the Mean | 0.3172 | 2-Sided | 95 | -0.966 | 0.361 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 100%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Median Difference (Net) | 0.204 | Standard Error of the Mean | 0.1841 | 2-Sided | 95 | -0.184 | 0.593 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 100%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.105 | Standard Error of the Mean | 0.1846 | 2-Sided | 95 | -0.284 | 0.494 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 100%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.416 | Standard Error of the Mean | 0.2602 | 2-Sided | 95 | -0.132 | 0.965 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 110%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.156 | Standard Error of the Mean | 0.8652 | 2-Sided | 95 | -0.650 | 2.961 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 110%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.518 | Standard Error of the Mean | 0.8324 | 2-Sided | 95 | -2.249 | 1.213 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 110%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.269 | Standard Error of the Mean | 1.0383 | 2-Sided | 95 | -2.436 | 1.898 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 110%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.806 | Standard Error of the Mean | 0.5862 | 2-Sided | 95 | -0.420 | 2.031 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 110%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.007 | Standard Error of the Mean | 0.5640 | 2-Sided | 95 | -1.183 | 1.168 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit | Superiority or Other |
| Stimulation Level 110%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.506 | Standard Error of the Mean | 0.7570 | 2-Sided | 95 | -0.064 | 3.077 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.644 | Standard Error of the Mean | 1.2976 | 2-Sided | 95 | -1.056 | 4.344 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.231 | Standard Error of the Mean | 1.1762 | 2-Sided | 95 | -2.681 | 2.219 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.184 | Standard Error of the Mean | 1.4796 | 2-Sided | 95 | -3.279 | 2.910 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.622 | Standard Error of the Mean | 0.9746 | 2-Sided | 95 | -1.428 | 2.672 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.602 | Standard Error of the Mean | 0.9340 | 2-Sided | 95 | -2.560 | 1.356 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 120%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 2.063 | Standard Error of the Mean | 1.2810 | 2-Sided | 95 | -0.610 | 4.736 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.556 | Standard Error of the Mean | 1.4588 | 2-Sided | 95 | -1.494 | 4.607 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.531 | Standard Error of the Mean | 1.2336 | 2-Sided | 95 | -3.102 | 2.041 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.185 | Standard Error of the Mean | 1.5697 | 2-Sided | 95 | -3.471 | 3.101 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.686 | Standard Error of the Mean | 1.2689 | 2-Sided | 95 | -1.996 | 3.367 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.556 | Standard Error of the Mean | 1.0822 | 2-Sided | 95 | -2.838 | 1.726 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 130%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 2.219 | Standard Error of the Mean | 1.4792 | 2-Sided | 95 | -0.884 | 5.322 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.631 | Standard Error of the Mean | 1.5890 | 2-Sided | 95 | -1.696 | 4.958 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.508 | Standard Error of the Mean | 1.2985 | 2-Sided | 95 | -3.219 | 2.203 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 4 Day 30 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.110 | Standard Error of the Mean | 1.6603 | 2-Sided | 95 | -3.369 | 3.588 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 0.852 | Standard Error of the Mean | 1.5675 | 2-Sided | 95 | -2.446 | 4.150 | Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | -0.357 | Standard Error of the Mean | 1.2918 | 2-Sided | 95 | -3.074 | 2.359 | Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
| Stimulation Level 140%, Visit 7 Day 112 | Mixed Model Repeated Measures Analysis | Mean Difference (Net) | 1.686 | Standard Error of the Mean | 1.7306 | 2-Sided | 95 | -1.937 | 5.308 | Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline | Superiority or Other |
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| Visit 1, Day 1- 1 hour post-dose |
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| Visit 1, Day 1 - 6 hour post-dose |
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| Visit 1, Day 1 - 24 hour post-dose |
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| Visit 2, Day 5 |
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| mRS Score 1 |
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| mRS Score 2 |
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| mRS Score 3 |
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| mRS Score 4 |
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| mRS Score 5 |
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